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N Engl J Med 378(16):1479–1493\nYannaki E, Papayannopoulou T, Jonlin E, Zervou F, Karponi G, Xagorari A, Becker P, Psatha N, Batsis I, Kaloyannidis P, Tahynopoulou V, Constantinou V, Bouinta A, Kotta K, Athanassiadou A, Anagnostopoulos A, Fassas A, Stamatoyannopoulos G (2012) Hematopoietic stem cell mobilization for gene therapy of adult patients with severe beta-thalassemia: results of clinical trials using G-CSF or plerixafor in splenectomized and nonsplenectomized subjects. Mol Ther 20(1):230–238\nSadelain M, Boulad F, Galanello R, Giardina P, Locatelli F, Maggio A, Rivella S, Riviere I, Tisdale J (2007) Therapeutic options for patients with severe beta-thalassemia: the need for globin gene therapy. Hum Gene Ther 18(1):1–9\nLiu J, Higgins CA, Whitehouse JC, Harris SJ, Crawford H, Christiano AM et al (2018) Hair follicle dermal cells support expansion of murine and human embryonic and induced pluripotent stem cells and promote haematopoiesis in mouse cultures. Stem Cells Int 2018:8631432\nRazaq MA, Taylor S, Roberts DJ, Carpenter L (2017) A molecular roadmap of definitive erythropoiesis from human induced pluripotent stem cells. Br J Haematol 176(6):971–983\nUnternaehrer JJ, Daley GQ (2011) Induced pluripotent stem cells for modelling human diseases. Philos Trans R Soc Lond Ser B Biol Sci 366(1575):2274–2285\nLiu YL, Yang Y, Kang XJ, Lin B, Yu Q, Song B, Gao G, Chen Y, Sun X, Li X, Bu L, Fan Y (2017) One-step biallelic and scarless correction of a beta-thalassemia mutation in patient-specific iPSCs without drug selection. Mol Ther-Nucl Acids 6:57–67\nLucarelli G, Clift RA, Galimberti M, Angelucci E, Giardini C, Baronciani D, Polchi P, Andreani M, Gaziev D, Erer B, Ciaroni A, D'Adamo F, Albertini F, Muretto P (1999) Bone marrow transplantation in adult thalassemic patients. Blood. 93(4):1164–1167\nThorvaldsdottir H, Robinson JT, Mesirov JP (2013) Integrative genomics viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform 14(2):178–192\nRobinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, Getz G et al (2011) Integrative genomics viewer. Nat Biotechnol 29(1):24–26\nNiu XH, He WY, Song B, Ou ZH, Fan D, Chen YC, Fan Y, Sun X (2016) Combining single strand oligodeoxynucleotides and CRISPR\u002FCas9 to correct gene mutations in beta-thalassemia-induced pluripotent stem cells. J Biol Chem 291(32):16576–16585\nKattamis AC, Camaschella C, Sivera P, Surrey S, Fortina P (1996) Human alpha-thalassemia syndromes: detection of molecular defects. Am J Hematol 53(2):81–91\nJang YY, Ye ZH (2016) Gene correction in patient-specific iPSCs for therapy development and disease modeling. Hum Genet 135(9):1041–1058\nSmith C, Abalde-Atristain L, He C, Brodsky BR, Braunstein EM, Chaudhari P, Jang YY, Cheng L, Ye Z (2015) Efficient and allele-specific genome editing of disease loci in human iPSCs. Mol Ther 23(3):570–577\nRaja JV, Rachchh MA, Gokani RH (2012) Recent advances in gene therapy for thalassemia. J Pharm Bioallied Sci 4(3):194–201\nDever DP, Bak RO, Reinisch A, Camarena J, Washington G, Nicolas CE, Pavel-Dinu M, Saxena N, Wilkens AB, Mantri S, Uchida N, Hendel A, Narla A, Majeti R, Weinberg KI, Porteus MH (2016) CRISPR\u002FCas9 beta-globin gene targeting in human haematopoietic stem cells. Nature. 539(7629):384–389\nCong L, Ran FA, Cox D, Lin SL, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR\u002FCas systems. Science. 339(6121):819–823\nHockemeyer D, Wang HY, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC, Zeitler B, Cherone JM, Meng X, Hinkley SJ, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29(8):731–734\nHockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver RC et al (2009) Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 27(9):851–U110\nChang CJ, Bouhassira EE (2012) Zinc-finger nuclease-mediated correction of alpha-thalassemia in iPS cells. Blood. 120(19):3906–3914\nMa N, Liao BJ, Zhang H, Wang LL, Shan YL, Xue YT, Huang K, Chen S, Zhou X, Chen Y, Pei D, Pan G (2013) Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free beta-thalassemia induced pluripotent stem cells. J Biol Chem 288(48):34671–34679\nMa N, Shan Y, Liao B, Kong G, Wang C, Huang K, Zhang H, Cai X, Chen S, Pei D, Chen N, Pan G (2015) Factor-induced reprogramming and zinc finger nuclease-aided gene targeting cause different genome instability in beta-thalassemia induced pluripotent stem cells (iPSCs). J Biol Chem 290(19):12079–12089\nXie F, Ye L, Chang JC, Beyer AI, Wang JM, Muench MO, Kan YW (2014) Seamless gene correction of beta-thalassemia mutations in patient-specific iPSCs using CRISPR\u002FCas9 and piggyBac. Genome Res 24(9):1526–1533\nKilpinen H, Goncalves A, Leha A, Afzal V, Alasoo K, Ashford S, Bala S, Bensaddek D, Casale FP, Culley OJ, Danecek P, Faulconbridge A, Harrison PW, Kathuria A, McCarthy D, McCarthy SA, Meleckyte R, Memari Y, Moens N, Soares F, Mann A, Streeter I, Agu CA, Alderton A, Nelson R, Harper S, Patel M, White A, Patel SR, Clarke L, Halai R, Kirton CM, Kolb-Kokocinski A, Beales P, Birney E, Danovi D, Lamond AI, Ouwehand WH, Vallier L, Watt FM, Durbin R, Stegle O, Gaffney DJ (2017) Common genetic variation drives molecular heterogeneity in human iPSCs (vol 546, pg 370, 2017). 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Xiaofang","ARTICLE",{"url":179,"publisher":366,"properties":412},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":367,"slug":10,"properties":368,"entityType":20,"verifyStatus":21,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":23,"subjectFields":372,"manageAffiliations":381,"indexDatabases":392,"url":22,"thumbnailPath":22,"statistic":407,"gsStatistic":22,"type":152,"analyzePriority":22},[],{"issn":369,"title":370,"eissn":371},{"VOID":15},{"EN":17},{"VOID":13},[373,377],{"id":26,"createTime":22,"updateTime":22,"relativeEntities":374,"label":375,"description":376,"parentId":22,"standard":22,"scholarHubFieldId":22},[],{"EN":29},{},{"id":32,"createTime":22,"updateTime":22,"relativeEntities":378,"label":379,"description":380,"parentId":22,"standard":22,"scholarHubFieldId":22},[],{"EN":35},{},[382,387],{"id":39,"createTime":22,"updateTime":22,"relativeEntities":383,"slug":22,"properties":384,"entityType":22,"verifyStatus":22,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":22,"url":22,"parentIds":386,"statistic":22},[],{"title":385},{"EN":43},[45],{"id":47,"createTime":22,"updateTime":22,"relativeEntities":388,"slug":22,"properties":389,"entityType":22,"verifyStatus":22,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":22,"url":22,"parentIds":391,"statistic":22},[],{"title":390},{"EN":51},[],[393,400],{"id":55,"indexDatabase":394,"url":66,"indexYears":67,"academicFieldIds":399,"indexDatabaseRanking":71},{"id":57,"createTime":22,"updateTime":22,"relativeEntities":395,"label":396,"description":397,"key":63,"publicationTags":398,"standard":22},[],{"EN":60,"VI":60},{"EN":60,"VI":62},[65],[69,70],{"id":73,"indexDatabase":401,"url":86,"indexYears":22,"academicFieldIds":406,"indexDatabaseRanking":22},{"id":75,"createTime":22,"updateTime":22,"relativeEntities":402,"label":403,"description":404,"key":82,"publicationTags":405,"standard":22},[],{"EN":78,"VI":78},{"EN":80,"VI":81},[84,85],[88],{"impactFactor":23,"impactFactorByYear":408,"i10Index":92,"i10IndexLast5Year":23,"totalPublication":93,"totalPublicationByYear":409,"totalCitation":144,"totalCitationByYear":410,"totalCitationPerPublication":23,"totalCitationPerPublicationByYear":411,"hindexLast5Year":92,"hindex":92},{"1971":91,"1972":91,"1987":91,"2021":23},{"1955":95,"1956":96,"1957":97,"1958":98,"1959":99,"1960":100,"1961":101,"1962":102,"1963":103,"1964":104,"1965":105,"1966":106,"1967":107,"1968":108,"1969":109,"1970":110,"1971":106,"1972":111,"1973":111,"1974":112,"1975":113,"1976":108,"1977":114,"1978":115,"1979":116,"1980":117,"1981":110,"1982":118,"1983":119,"1984":117,"1985":118,"1986":119,"1987":118,"1988":110,"1989":118,"1990":105,"1991":118,"1992":120,"1993":108,"1994":121,"1995":122,"1996":113,"1997":123,"1998":117,"1999":124,"2000":109,"2001":125,"2002":116,"2003":126,"2004":115,"2005":121,"2006":127,"2007":128,"2008":129,"2009":130,"2010":131,"2011":131,"2012":132,"2013":133,"2014":134,"2015":135,"2016":136,"2017":137,"2018":138,"2019":139,"2020":140,"2021":141,"2022":142,"2023":143,"2024":118},{"1970":146,"1985":147,"2019":148},{"1970":150,"1985":151,"2019":91},{"pages":413,"volume":415},{"VOID":414},"2661-2671",{"VOID":416},"98","2019-09-09",2019,[84,71],false,{"id":422,"createTime":423,"updateTime":424,"relativeEntities":425,"slug":426,"properties":427,"entityType":173,"verifyStatus":174,"verifyTime":437,"verifyNote":176,"languages":22,"translateLanguages":438,"viewCount":23,"primaryUrl":439,"fullTextUrl":22,"authors":440,"publicationType":364,"publisherRelationship":482,"citationCount":22,"citationInfo":22,"publishDate":534,"publishYear":535,"citationAnalyzeStatus":21,"lastCitationAnalyze":22,"indexDatabases":536,"openAccess":22,"references":22,"isForceReanalyzing":420},"f64640be-0e83-4db3-8348-255a915c3734","2024-01-26T09:50:43.727+00:00","2026-09-10T07:12:06.782+00:00",[],"RNA-interference-RNAi-in-hematology",{"abstract":428,"title":430,"references":433,"doi":435},{"EN":429},"RNA interference (RNAi), an evolutionary highly conserved process of post-transcriptional gene silencing, can be triggered by small interfering RNAs (siRNAs) that mediate sequence-specific mRNA degradation. Since the first reports in 1998, RNAi has rapidly been developed into an effective tool to specifically knock down gene expression in a wide variety of target cells. Accordingly, RNAi is currently used for both systematic functional genomics in several organisms and for specific therapeutic intervention in preclinical models of different diseases characterized by aberrant gene expression. However, since siRNAs are not replicated in mammalian cells during the process of RNAi, kinetic aspects of RNAi-induced gene silencing that eventually depend on the intracellular level of siRNA must be considered for each analytical or therapeutic application in these cells. We summarize here some aspects of siRNA design and delivery, of RNAi kinetics, potential side effects, and limitations of siRNA-mediated gene silencing, as well as putative RNAi targets for functional and\u002For therapeutic intervention in hematopoietic cells.",{"EN":431,"VI":432},"RNA interference (RNAi) in hematology","RNA can thiệp (RNAi) trong huyết học",{"VOID":434},"Abbas-Terki T, Blanco-Bose W, Deglon N, Pralong W, Aebischer P (2002) Lentiviral-mediated RNA interference. Hum Gene Ther 13:2197–2201\nArteaga HJ, Hinkula J, Van Dijk-Hard I, Dilber MS, Wahren B, Christensson B, Mohamed AJ, Edvard Smith CI (2003) Choosing CCR5 or Rev siRNA in HIV-1. Nat Biotechnol 21:230–231\nAshrafi K, Chang FY, Watts JL, Fraser AG, Kamath RS, Ahringer J, Ruvkun G (2003) Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421:268–1272\nBanerjea A, Li MJ, Bauer G, Remling L, Lee NS, Rossi J, AkkinaR (2003) Inhibition of HIV-1 by lentiviral vector-transduced siRNAs in T lymphocytes differentiated in SCID-hu mice and CD34(+) progenitor cell-derived macrophages. Mol Ther 8:62–71\nBarton GM, Medzhitov R (2002) Retroviral delivery of small interfering RNA into primary cells. Proc Natl Acad Sci U S A 99:14943–14945\nBennett CF, Chiang MY, Chan H, Shoemaker JE, Mirabelli CK (1992) Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides Mol Pharmacol 41:1023–1033\nBennett CF, Mirejovsky D, Crooke RM, Tsai YJ, Felgner J, Sridhar CN, Wheeler CJ, Felgner PL (1998) Structural requirements for cationic lipid mediated phosphorothioate oligonucleotides delivery to cells in culture. J Drug Target 5:149–162\nBernstein E, Caudy AA, Hammond SM, Hannon GJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–366\nBrummelkamp TR, Bernards R, Agami R (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550–553\nBrummelkamp TR, Bernards R, Agami R (2002) Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell 2:243–247\nCaplen NJ, Parrish S, Imani F, Fire A, Morgan RA (2001) Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems. Proc Natl Acad Sci U S A 98:9742–9747\nCapodici J, Kariko K, Weissman D (2002) Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J Immunol 169:5196–5201\nChi JT, Chang HY, Wang NN, Chang DS, Dunphy N, Brown PO (2003) Genomewide view of gene silencing by small interfering RNAs. Proc Natl Acad Sci U S A 100:6343–6346\nCioca DP, Aoki Y, Kiyosawa K (2003) RNA interference is a functional pathway with therapeutic potential in human myeloid leukemia cell lines. Cancer Gene Ther 10:125–133\nCoburn GA, Cullen BR (2002) Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference. J Virol 76:9225–9231\nCogoni C, Irelan JT, Schumacher M, Schmidhauser TJ, Selker EU, Macino G (1996) Transgene silencing of the al-1 gene in vegetative cells of Neurospora is mediated by a cytoplasmic effector and does not depend on DNA-DNA interactions or DNA methylation. EMBO J 15:3153–3163\nCzauderna F, Fechtner M, Aygun H, Arnold W, Klippel A, Giese K, Kaufmann J (2003) Functional studies of the PI(3)-kinase signalling pathway employing synthetic and expressed siRNA. Nucleic Acids Res 31:670–682\nDevroe E, Silver PA (2002) Retrovirus-delivered siRNA. BMC Biotechnology 2:15\nDonze O, Picard D (2002) RNA interference in mammalian cells using siRNAs synthesized with T7 RNA polymerase. Nucleic Acids Res 30:e46\nDykxhoorn DM, Novina CD, Sharp PA (2003) Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol 4:457–467\nElbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498\nElbashir SM, Lendeckel W, Tuschl T (2001) RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15:188–200\nElbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T (2001) Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J 20:6877–6888\nFerrari ME, Nguyen CM, Zelphati O, Tsai Y, Felgner PL (1998) Analytical methods for the characterization of cationic lipid-nucleic acid complexes. Hum Gene Ther 9:341–351\nFire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811\nFraser AG, Kamath RS, Zipperlen P, Martinez-Campos M, Sohrmann M, Ahringer J (2000) Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408:325–330\nGitlin L, Karelsky S, Andino R (2002) Short interfering RNA confers intracellular antiviral immunity in human cells. Nature 418:430–434\nGonczy P, Echeverri C, Oegema K, Coulson A, Jones SJ, Copley RR, Duperon J, Oegema J, Brehm M, Cassin E, Hannak E, Kirkham M, Pichler S, Flohrs K, Goessen A, Leidel S, Alleaume AM, Martin C, Ozlu N, Bork P, Hyman AA (2000) Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III. Nature 408:331–336\nGrant CE, Vasa MZ, Deeley RG (1995) cIRF-3, a new member of the interferon regulatory factor (IRF) family that is rapidly and transiently induced by dsRNA. 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Blood 101:3157–3163\nHeinonen JE, Smith CI, Nore BF (2002) Silencing of Bruton’s tyrosine kinase (Btk) using short interfering RNA duplexes (siRNA). FEBS Lett 527:274–278\nHemann MT, Fridman JS, Zilfou JT, Hernando E, Paddison PJ, Cordon-Cardo C, Hannon GJ, Lowe SW (2003) An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo. Nat Genet 33:396–400\nHill JA, Ichim TE, Kusznieruk KP, Li M, Huang X, Yan X, Zhong R, Cairns E, Bell DA, Min WP (2003) Immune modulation by silencing IL-12 production in dendritic cells using small interfering RNA. J Immunol 171:691–696\nHofmann WK, de Vos S, Elashoff D, Gschaidmeier H, Hoelzer D, Koeffler HP, Ottmann OG (2002) Relation between resistance of Philadelphia-chromosome-positive acute lymphoblastic leukaemia to the tyrosine kinase inhibitor STI571 and gene-expression profiles: a gene-expression study. Lancet 359:481–486\nHolen T, Amarzguioui M, Wiiger MT, Babaie E, Prydz H (2002) Positional effects of short interfering RNAs targeting the human coagulation trigger tissue factor. Nucleic Acids Res 30:1757–1766\nJackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, Mao M, Li B, Cavet G, Linsley PS (2003) Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21:635–637\nJacque JM, Triques K, Stevenson M (2002) Modulation of HIV-1 replication by RNA interference. Nature 418:435–438\nKamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, Kanapin A, Le Bot N, Moreno S, Sohrmann M, Welchman DP, Zipperlen P, Ahringer J (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421:231–237\nKaufman RJ (1999) Double-stranded RNA-activated protein kinase mediates virus-induced apoptosis: a new role for an old actor. Proc Natl Acad Sci U S A 96:11693–11695\nKawasaki H, Suyama E, Iyo M, Taira K (2003) siRNAs generated by recombinant human Dicer induce specific and significant but target site-independent gene silencing in human cells. Nucleic Acids Res 31:981–987\nKunath T, Gish G, Lickert H, Jones N, Pawson T, Rossant J (2003) Transgenic RNA interference in ES cell-derived embryos recapitulates a genetic null phenotype. Nat Biotechnol 21:559–561\nLee NS, Dohjima T, Bauer G, Li H, Li MJ, Ehsani A, Salvaterra P, Rossi J (2002) Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol 20:500–505\nLewis DL, Hagstrom JE, Loomis AG, Wolff JA, Herweijer H (2002) Efficient delivery of siRNA for inhibition of gene expression in postnatal mice. Nat Genet 32:107–108\nLindbo JA, Dougherty WG (1992) Untranslatable transcripts of the tobacco etch virus coat protein gene sequence can interfere with tobacco etch virus replication in transgenic plants and protoplasts. Virology 189:725–733\nMartinez MA, Gutierrez A, Armand-Ugon M, Blanco J, Parera M, Gomez J, Clotet B, Este JA (2002) Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication. AIDS 16:2385–2390\nMatta H, Hozayev B, Tomar R, Chugh P, Chaudhary PM (2003) Use of lentiviral vectors for delivery of small interfering RNA. Cancer Biol Ther 2:206–210\nMcCaffrey AP, Meuse L, Pham TT, Conklin DS, Hannon GJ, Kay MA (2002) RNA interference in adult mice. Nature 418:38–39\nMcManus MT, Haines BB, Dillon CP, Whitehurst CE, van Parijs L, Chen J, Sharp PA (2002) Small interfering RNA-mediated gene silencing in T lymphocytes. J Immunol 169:5754–5760\nMiyagishi M, Taira K (2002) U6 promoter-driven siRNAs with four uridine 3’ overhangs efficiently suppress targeted gene expression in mammalian cells. Nat Biotechnol 20:497–500\nNapoli C, Lemieux C, Jorgensen R (1990) Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. Plant Cell 2:279–289\nNovina CD, Murray MF, Dykxhoorn DM, Beresford PJ, Riess J, Lee SK, Collman RG, Lieberman J, Shankar P, Sharp PA (2002) siRNA-directed inhibition of HIV-1 infection. Nat Med 8:681–686\nNur-E-Kamal A, Tsai-Kun L, Zhang A, Qi H, Hars E, Liu LF (2003) Single-stranded DNA induces ATM\u002Fp53-dependent DNA damage and apoptotic signals. J Biol Chem 278:12475–12481\nNykanen A, Haley B, Zamore PD (2001) ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107:309–321\nPaddison PJ, Hannon GJ (2002) RNA interference: the new somatic cell genetics? Cancer Cell 2:17–23\nPatterson RL, van Rossum DB, Ford DL, Hurt KJ, Bae SS, Suh PG, Kurosaki T, Snyder SH, Gill DL (2002) Phospholipase C-gamma is required for agonist-induced Ca2+ entry. Cell 111:529–541\nPaul CP, Good PD, Winer I, Engelke DR (2002) Effective expression of small interfering RNA in human cells. Nat Biotechnol 20:505–508\nPlasterk RH (2002) RNA silencing: the genome’s immune system. Science 296:1263–1265\nQin XF, An DS, Chen IS, Baltimore D (2003) Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci U S A 100:183–188\nRubinson DA, Dillon CP, Kwiatkowski AV, Sievers C, Yang L, Kopinja J, Rooney DL, Ihrig MM, McManus MT, Gertler FB, Scott ML, Van Parijs L (2003) A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. 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Proc Natl Acad Sci U S A 99:6047–6052\nZamore PD (2002) Ancient pathways programmed by small RNAs. Science 296:1265–1269",{"VOID":436},"10.1007\u002Fs00277-003-0759-1","2024-12-05T19:27:45.728+00:00",[178],"https:\u002F\u002Flink.springer.com\u002Farticle\u002F10.1007\u002Fs00277-003-0759-1",[441,456,469],{"id":442,"sortIndex":23,"researcher":22,"roles":443,"affiliations":444,"properties":453,"displayName":455,"givenName":22,"familyName":22},"1f02d309-39a8-4085-94b1-638bcd20360c",[184],[445],{"id":446,"sortIndex":23,"affiliation":447,"properties":22},"af63d585-ca38-4a05-9005-e9445f970aed",{"id":446,"createTime":22,"updateTime":22,"relativeEntities":448,"slug":22,"properties":449,"entityType":22,"verifyStatus":22,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":22,"url":22,"parentIds":452,"statistic":22},[],{"title":450},{"VI":451},"Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany",[],{"title":454},{"VI":455},"M. 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The specificity of the anti-HCV screening in low seroprevalence populations has been questioned. In order to evaluate this screening policy we wanted to estimate the prevalence of viremic and potentially infectious donors by the HCV-RNA polymerase chain reaction (PCR) in our donor population of southern Germany. Donors (n=301) were divided into four subgroups according to anti-HCV status and ALT levels. HCV sequences were detected by nested PCR, using primers for the most conserved region of the viral genome. The recombinant immunoblot assay (RIBA-4) was applied to the same samples. PCR detected 4.2% HCV-RNA carriers in the subgroup anti-HCV−\u002FALT−; 3% in the subgroup anti-HCV−\u002FALT+; 19.4% in the subgroup anti-HCV+\u002FALT−; and 59.4% in the subgroup anti-HCV+\u002FALT+. It was concluded that, on the one hand, the lack of specificity of the anti-HCV ELISA gives rise to many false-positive results; on the other hand, a minority of infected donations will not be detected by the screening procedure. ALT in conjunction with anti-HCV improves the quality of screening for potentially infectious donors.",{"EN":817},"Prevalence of HCV-RNA-positive blood donors and correlation to ELISA and RIBA status",{"VOID":819},"[]",{"VOID":821},"Alter HJ, Purcell RH, Shih JW, Melpolder JC, Houghton M, Choo Q-L, Kuo G (1989) Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med 2: 321: 1494–1500\nAlter MJ, Hadler SC, Judson FN, Mares A, Alexander WJ, Hu PY, Miller JK, Moyer LA, Fields HA, Bradley DW, Margolis HS (1990) Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. JAMA 264: 2231–2235\nBeenhouwer H De, Verhaert H, Clays H, Vermylen C (1992) Confirmation of hepatitis C virus-positive blood donors by immunoblotting and polymerase chain reaction. Vox Sang 63: 198–203\nCardoso MS, Epple S, Koerner K, Kubanek B, Ellbrück D, Seifried E (1991) Investigating the presence of HIV sequences and the distribution of virological markers in hemophiliacs and their sexual partners. Ann Hematol 63: 315–319\nCardoso MS, Jochem H, Hesse R, Epple S, Koerner K, Kubanek B (1992) Evaluating recombinant protein immunoblot assay and polymerase chain reaction for diagnosis of non-A, non-B hepatitis. J Infect Dis 166: 450–451\nChan S-W, Simmonds P, McOmisch F, Yap P-L, Mitchell R, Dow B, Follett E (1991) Serological responses to infection with three different types of hepatitis C virus. Lancet 338: 1391\nChomczynski P, Sacchi N (1987) Single-step method for RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159\nChoo QL, Richman KH, Han JH, Berger K, Lee C, Dong C, Gallegos C, Coit D, Medina-Selby A, Barr PJ, Weiner AJ, Bradley DW, Kuo G, Houghton M (1991) Genetic organization and diversity of hepatitis C virus. Proc Natl Acad Sci USA 88: 2451–2455\nCouroucé A-M, Janot C and the Hepatitis Study Group of the French Society of Blood Transfusion (1991) Recombinant immunoblot assay first and second generations on 732 blood donors reactive for antibodies to hepatitis C virus by ELISA. Vox Sang 61: 177–180\nDengler T, Kellner S, Fürst G (1991) Erfahrungen mit einer einfachen Mikrotiterplatten-Technik für das GPT-“Screening” bei Blutspendern. Infusionstherapie 19: 76–78\nFarci P, Alter HJ, Wong D, Miller RH, Shih JW, Jett B, Purcell RH (1991) A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med 325: 98–104\nFrösner GG (1991) Sensitivity of second-generation anti-HCV test for diagnosis of acute hepatitis C. Infection 19: 434\nGarson JA, Ring C, Tuke P, Tedder RS (1990) Enhanced detection by PCR of hepatitis C virus RNA. Lancet 336: 878–879\nKuo G, Choo Q-L, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Altger MJ, Stevens CE, Tegtmeier GE, Bonino T, Colombo M, Lee W-S, Kuo C, Berger K, Shuster JR, Overby LR, Bradley DW, Houghton M (1989) An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244: 362–364\nKwok S, Higuchi R (1989) Avoiding false positives with PCR. Nature 339: 237–238\nMcHutchinson JG, Person JL, Govindarajan S, Valinluck B, Gore T, Lee SR, Nelles M, Polito A, Chien D, Di Nello, Quan S, Kuo G, Redeker AG (1992) Improved detection of hepatitis C virus antibodies in high-risk populations. Hepatology 15: 19–25\nNicholson S, Leslie DE, Efandis T, Fairley CK, Gust ID (1991) Hepatitis C antibody-testing: problems associated with nonspecific binding. J Virol Methods 33: 311–317\nOkamoto H, Okada S, Sugiyama Y, Tanaka T, Sugai Y, Akahane Y, Machida A, Mishiro S, Yoshizawa H, Miyakawa Y, Mayumi M (1990) Detection of hepatitis C virus RNA by a twostage polymerase chain reaction with two pairs of primers deduced from the 5′-noncoding region. Jpn J Exp Med 60: 215–222\nOkamoto H, Okada S, Sugiyama Y, Yotsumoto S, Tanaka T, Yoshizawa H, Tsuda F, Miyakawa Y, Mayumi M (1990) The 5′-terminal sequence of the hepatitis C virus genome. Jpn J Exp Med 60: 167–177\nPoel CL Van der, Reesink HW, Schaasberg W, Leentvaar-Kuypers A, Bakker E, Exel-Oehlers PJ, Lelie PN (1990) Infectivity of blood seropositive for hepatitis C virus antibodies. Lancet 335: 558–560\nPoel CL Van der, Cuypers HTM, Reesink HW, Weiner AJ, Quan S, di Nello R, van Boven JJP, Winkel I, Mulder-Folkerts D, Exel-Oehlers PJ, Schaasberg W, Leentvaar-Kuypers A, Polito A, Houghton M, Lelie PN (1991) Confirmation of hepatitis C virus infection by new four-antigen recombinant immunoblot assay. Lancet 337: 317–319\nWidell A, Mansson A-S, Sundström G, Hanssen BG, Nordenfelt E (1991) Hepatitis C virus RNA in blood donor sera detected by the polymerase chain reaction: comparison with supplementary hepatitis C antibody assays. J Med Virol 35: 253–258\nZanetti AR, Tanzi E, Zehender G, Magni E, Incarbone C, Zonaro A, Primi D, Cariani E (1990) Hepatitis C virus RNA in symptomless donors implicated in post-transfusion non-A, non-B hepatitis. 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In Ethiopia, as in most low- and middle-income countries (LMICs), access to standard diagnostic, follow-up, and prognostic tools is very limited, and it has been challenging to strictly follow international guidelines. This seriously compromises clinical outcome, despite the availability of TKIs through the Glivec International Patient Assistance Program (GIPAP). Multiplex PCR (mpx-PCR), conventionally regarded as a “screening tool,” offers a potential solution to this problem. A total of 219 samples from confirmed CML patients were assayed. In reference to qRT-PCR, the AUC of ROC curve for mpx-PCR was 0.983 (95% CI: 0.957 to 0.997). At the optimum cut-off value, equivalent to BCR::ABL1 (IS) transcript copy number of 0.6%, the specificity and sensitivity were 93% and 95%, respectively, with 94% accuracy. Albeit the sensitivity and accuracy of mpx-PCR decrease below the optimum cutoff of 0.6% (IS), the specificity at 0.1% (IS) was 100%, making it an attractive means to rule-out relapse and drug non-adherence at later stages of treatment, which is particularly an issue in a low income setting. 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The special sampling technique using fine capillary tubes and a successive simple concentration reveals optimal results. The presented method can also be implied on otherwise suspended cell assays as blood, liquor, exsudates, perfusates and tissue-culture mediums.",{"EN":1481},"A new method for sequential detection of bone marrow cells in small laboratory animals",{"VOID":1483},"13882968666443802031",{"VOID":1485},"10.1007\u002FBF01675274","2024-04-28T11:48:13.994+00:00","https:\u002F\u002Flink.springer.com\u002Farticle\u002F10.1007\u002FBF01675274",[1489,1504],{"id":1490,"sortIndex":23,"researcher":22,"roles":1491,"affiliations":1492,"properties":1501,"displayName":1503,"givenName":22,"familyName":22},"605f2ab2-2b83-4b71-87e4-04fa1b7c16ca",[184],[1493],{"id":1494,"sortIndex":23,"affiliation":1495,"properties":22},"50840f17-ebdb-4126-aebd-cf46b9df99be",{"id":1494,"createTime":22,"updateTime":22,"relativeEntities":1496,"slug":22,"properties":1497,"entityType":22,"verifyStatus":22,"verifyTime":22,"verifyNote":22,"languages":22,"translateLanguages":22,"viewCount":22,"url":22,"parentIds":1500,"statistic":22},[],{"title":1498},{"VI":1499},"Institute of Pathology, University of Kiel, Kiel",[],{"title":1502},{"VI":1503},"J. 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Blood 85(4):885–892\nNavenot JM et al (1993) Rapid diagnosis of paroxysmal nocturnal hemoglobinuria by gel test agglutination. Rev Fr Transfus Hemobiol 36(2):135–147\nNakayama H et al (2016) Eculizumab dosing intervals longer than 17 days may be associated with greater risk of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria. Biol Pharm Bull 39(2):285–288\nRisitano AM et al (2009) Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood 113(17):4094–4100\nHochsmann B et al (2012) Paroxysmal nocturnal haemoglobinuria treatment with eculizumab is associated with a positive direct antiglobulin test. Vox Sang 102(2):159–166\nLuzzatto L (2016) Recent advances in the pathogenesis and treatment of paroxysmal nocturnal hemoglobinuria. F1000Res p 5. doi:10.12688\u002Ff1000research.7288.1\nGargiulo L et al (2007) Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria. Blood 109(11):5036–5042\nGargiulo L et al (2013) Glycosylphosphatidylinositol-specific, CD1d-restricted T cells in paroxysmal nocturnal hemoglobinuria. 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of the long arm of chromosome 20 with interstitial loss of material [ider(20q)] is a rare cytogenetic abnormality reported in myelodysplastic syndrome (MDS), with neither specific morphological pattern nor clear prognostic significance. The aim of this retrospective multicentric study is to compare the peripheral blood and bone marrow morphology of MDS patients with ider(20q) (n = 13) and del(20q) (n = 21) and controls (n = 47) in order to investigate whether the ider(20q) harbors specific morphological features. The secondary objective is to compare the outcome of patients from both groups. This study performed on the largest cohort of MDS patients with ider(20q) is the first that identifies specific morphological features (hypogranulated and vacuolized neutrophils and neutrophil erythrophagocytosis) allowing the identification of this cytogenetic abnormality with high sensitivity (70%) and specificity (85.7%). Suspected ider(20q) by morphology should therefore support targeted FISH tests in case of non informative karyotype. This combined approach will allow a better estimation of the prevalence of this underdiagnozed entity. The overall survival and progression-free survival did not statistically differ in both groups. However, hypogranulated and vacuolized neutrophils were significantly associated with survival.",{"EN":1735},"Morphology, cytogenetics, and survival in myelodysplasia with del(20q) or ider(20q): a multicenter study",{"VOID":1737},"[\"14666026687599993126\"]",{"VOID":1739},"Li T, Xue Y, Wu Y, Pan J (2004) Clinical and molecular cytogenetic studies in seven patients with myeloid diseases characterized by i(20q-). Br J Haematol 125(3):337–342\nDouet-Guilbert N, Lai JL, Basinko A, Gueganic N, Andrieux J, Pollet B, Plantier I, Delattre C, Crepin O, Corm S, Le Bris MJ, Morel F, De Braekeleer M (2008) Fluorescence in situ hybridization characterization of ider(20q) in myelodysplastic syndrome. Br J Haematol 143(5):716–720\nLigon AH, DeAngelo DJ, Atkins L, Dal Cin P (2005) Isochromosome of a deleted 20q may be a relatively common abnormality in myeloid malignancies. Cancer Genet Cytogenet 162(1):89–91\nMacKinnon RN, Campbell LJ (2005) A comparison of two contrasting recurrent isochromosomes 20 found in myelodysplastic syndromes suggests that retention of proximal 20q is a significant factor in myeloid malignancies. Cancer Genet Cytogenet 163(2):176–179\nSaunders K, Czepulkowski B, Sivalingam R, Hayes JP, Aldouri M, Sekhar M, Cummins M, Ho A, Mufti GJ (2005) Isochromosome of a deleted 20q: a rare but recurrent chromosome abnormality in myelodysplastic syndromes. Cancer Genet Cytogenet 156(2):154–157\nSmoley SA, Fink SR, Paternoster SF, Stockero KJ, Nguyen LP, Nguyen PL, Hanson CA, Dewald GW (2007) Frequency, hematopathology, and detection of a new isodicentric variant of deletion 20q. Cancer Genet Cytogenet 173(2):144–149\nXue Y, Han Y, Li T, Chen S, Zhang J, Pan J, Wu Y, Wang Y, Shen J (2010) Pulmonary alveolar proteinosis as a terminal complication in a case of myelodysplastic syndrome with idic(20q-). Acta Haematologica 123(1):55–58\nShetty S, Roland B (2008) Isoderivative chromosome 20 in bone marrow: three new cases. Cancer Genet Cytogenet 184(1):72–73\nLim TH, Lim AS, Tien SL (2006) A novel isoderivative chromosome 20 in a patient with chronic myelomonocytic leukemia. Cancer Genet Cytogenet 170(1):80–82\nLi T, Xue Y, Zhang J, Chen S, Pan J, Wu Y, Wang Y, Shen J (2008) Isodicentric 20q- in two cases of b-cell acute lymphocytic leukemia with the respective t(9;20)(p11;q11.2) and t(9;22)(q34;q11.2). Cancer Genet Cytogenet 181(1):55–59\nKurtin PJ, Dewald GW, Shields DJ, Hanson CA (1996) Hematologic disorders associated with deletions of chromosome 20q: a clinicopathologic study of 107 patients. Am J Clin Pathol 106(5):680–688\nSwerdlow S, Campo E, Harris N-L, Jaffe E-S, Pileri S-A, Stein H, Thiele J, Vardiman J-W (2008) Who classification of tumours of haematopoietic and lymphoid tissues. First published, Lyon\nHur M, Lee KM, Cho HC, Park YI, Kim SH, Chang YW, Kim YR, Cho HI (2004) Protein 4.1 deficiency and deletion of chromosome 20q are associated with acquired elliptocytosis in myelodysplastic syndrome. Clin Lab Haematol 26(1):69–72\nIshida F, Shimodaira S, Kobayashi H, Saito H, Kaku M, Kanzaki A, Yawata Y, Kitano K, Kiyosawa K (1999) Elliptocytosis in myelodysplastic syndrome associated with translocation (1;5)(p10;q10) and deletion of 20q. Cancer Genet Cytogenet 108(2):162–165\nBrezinova J, Zemanova Z, Ransdorfova S, Sindelarova L, Siskova M, Neuwirtova R, Cermak J, Michalova K (2005) Prognostic significance of del(20q) in patients with hematological malignancies. Cancer Genet Cytogenet 160(2):188–192\nCampbell LJ, Garson OM (1994) The prognostic significance of deletion of the long arm of chromosome 20 in myeloid disorders. Leukemia 8(1):67–71\nGreenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89(6):2079–2088\nLiu YC, Ito Y, Hsiao HH, Sashida G, Kodama A, Ohyashiki JH, Ohyashiki K (2006) Risk factor analysis in myelodysplastic syndrome patients with del(20q): prognosis revisited. Cancer Genet Cytogenet 171(1):9–16\nHaase D (2008) Cytogenetic features in myelodysplastic syndromes. Ann Hematol 87(7):515–526\nHaase D, Germing U, Schanz J, Pfeilstocker M, Nosslinger T, Hildebrandt B, Kundgen A, Lubbert M, Kunzmann R, Giagounidis AA, Aul C, Trumper L, Krieger O, Stauder R, Muller TH, Wimazal F, Valent P, Fonatsch C, Steidl C (2007) New insights into the prognostic impact of the karyotype in mds and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 110(13):4385–4395\nLi T, Xue Y, Wu Y, Pan J (2006) Fish studies identify the i(20q-) anomaly as a der(20)del(20)(q11q13)idic(20)(p11). Genes Chromosomes Cancer 45(6):536–539\nAsimakopoulos FA, Green AR (1996) Deletions of chromosome 20q and the pathogenesis of myeloproliferative disorders. Br J Haematol 95(2):219–226\nWattel E, Lai JL, Hebbar M, Preudhomme C, Grahek D, Morel P, Bauters F, Fenaux P (1993) De novo myelodysplastic syndrome (mds) with deletion of the long arm of chromosome 20: a subtype of mds with distinct hematological and prognostic features? Leuk Res 17(11):921–926\nValent P, Horny HP (2009) Minimal diagnostic criteria for myelodysplastic syndromes and separation from icus and idus: update and open questions. Eur J Clin Invest 39(7):548–553\nLesesve JF, Garand R (2009) Evaluation of a telemedicine system for the transmission of morpho\u002Fimmunological data aiming at the inclusion of patients in a therapeutic trial. Intern J Telemed Appl 2009:767145\nShaffer LG, Clovak ML, Campbell LJ (eds) (2009) An International System for Human Cytogenetic Nomenclature (ISCN) (2009). Karger, Basel\nDouet-Guilbert N, Andrieux J, Lai JL, Morice P, Demory JL, Basinko A, Ugo V, Gueganic N, Le Bris MJ, Morel F, De Braekeleer M (2009) Isoderivative of deleted chromosome 20 in primary myelofibrosis (pmf) characterized by molecular cytogenetics and array cgh. Ann Hematol 88(11):1157–1159\nBain B (2006) Disorders of white cells. In: Blood cells—a practical guide. Blackwell, Oxford, UK, p 398\nMermel CH, McLemore ML, Liu F, Pereira S, Woloszynek J, Lowell CA, Link DC (2006) Src family kinases are important negative regulators of g-csf-dependent granulopoiesis. Blood 108(8):2562–2568\nAscani S, Sabattini E, Agostinelli C, Piccaluga PP, Zinzani PL, Pileri SA (2004) Erythrophagocytosis by neoplastic cells in a patient with myelodysplastic syndrome. Haematologica 89(4):EIM07\nMori H, Tawara M, Yoshida Y, Kuriyama K, Sugahara K, Kamihira S, Tomonaga M (2000) Minimally differentiated acute myeloid leukemia (aml-m0) with extensive erythrophagocytosis and del(20)(q11) chromosome abnormality. Leuk Res 24(1):87–90\nEtzell J, Lu CM, Browne LW, Wang E (2005) Erythrophagocytosis by dysplastic neutrophils in chronic myelomonocytic leukemia and subsequent transformation to acute myeloid leukemia. Am J Hematol 79(4):340–342\nKuyama J, Fushino M, Take H, Kanayama Y (1995) Myelodysplastic syndrome associated with erythrophagocytosis by blasts and myeloid cells. Int J Hematol 62(4):243–246\nMoretti S, Lanza F, Spisani S, Latorraca A, Rigolin GM, Giuliani AL, Castoldi GL, Traniello S (1994) Neutrophils from patients with myelodysplastic syndromes: relationship between impairment of granular contents, complement receptors, functional activities and disease status. Leuk Lymphoma 13(5–6):471–477\nOhsaka A, Saionji K, Igari J, Watanabe N, Iwabuchi K, Nagaoka I (1997) Altered surface expression of effector cell molecules on neutrophils in myelodysplastic syndromes. Br J Haematol 98(1):108–113\nAn X, Mohandas N (2008) Disorders of red cell membrane. Br J Haematol 141(3):367–375\nDouet-Guilbert N, Basinko A, Morel F, Le Bris MJ, Ugo V, Morice P, Berthou C, De Braekeleer M (2008) Chromosome 20 deletions in myelodysplastic syndromes and philadelphia-chromosome-negative myeloproliferative disorders: characterization by molecular cytogenetics of commonly deleted and retained regions. Ann Hematol 87(7):537–544\nSoupir CP, Vergilio JA, Kelly E, Dal Cin P, Kuter D, Hasserjian RP (2009) Identification of del(20q) in a subset of patients diagnosed with idiopathic thrombocytopenic purpura. Br J Haematol 144(5):800–802\nVoulgarelis M, Giannouli S, Ritis K, Tzioufas AG (2004) Myelodysplasia-associated autoimmunity: clinical and pathophysiologic concepts. 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pediatric chemotherapy regimens to treat adolescents and young adults (AYA) patients with Philadelphia negative acute lymphoblastic leukemia (ALL) have been associated with better outcomes. The local BFM 2009-based scheme complements the risk stratification assessing the measurable residual disease (MRD) along the induction phase with increasing levels of sensitivity. The present retrospective multicenter analysis included 171 AYA (15–40 years) patients treated accordingly between 2013 and 2019. Ninety-one percent obtained morphological complete remission, 67% a negative (\u003C0.1%) MRD at day 33 (TP1), and 78% a negative (\u003C0.01%) MRD at day 78 (TP2). The overall survival (OS) and the event-free survival (EFS) at 2 years were 62%±4.1 and 55%±4.1, respectively. The OS and EFS were significant better for prednisone responders, who achieved \u003C10% BM blast at day 15, a negative MRD at TP1 or at TP2, and for low-risk patients. Age ≤30 years and WBC \u003C30×109\u002FL, particularly among B-phenotype, were also associated with longer OS. In the multivariable analyses, TP1 MRD positive (OS HR 2.8, 95% CI 1.4–5.7, p=0.004; EFS HR 3.0, 95% CI 1.6–5.7, p=0.001) and at TP2 (OS HR 2.6, 95% CI 1.3–5.3, p=0.012; EFS HR 2.6, 95% CI 1.3–5.1, p=0.006) were independently associated with earlier events. Age >30 years was also associated with a shorter survival (HR 3.1, 95% CI 1.3–7.5, p=0.014). Therefore, those 68 patients ≤30 years with TP1\u002FTP2 negative MRD depicted a longer OS (2 years 85%±4.8). Based on our real-world data, the pediatric-based scheme is feasible in Argentina associated with better outcomes for younger AYA patients who achieved negative MRD at day 33 and 78.",{"EN":2009},"PH negative acute lymphoblastic leukemia in adolescents and young adults treated according a MRD adapted BFM ALL IC 2009 protocol: Argentine real-world data on 171 patients",{"VOID":2011},"[\"14220399040751721791\"]",{"VOID":2013},"Pui CH (2020) Precision medicine in acute lymphoblastic leukemia. Front Med 14:689–700. https:\u002F\u002Fdoi.org\u002F10.1007\u002Fs11684-020-0759-8\nSasaki K, Jabbour EJ, Short NJ, Jain N, Ravandi F, Pui CH, Kantarjian H (2021) Acute lymphoblastic leukemia: a population-based study of outcome in the United States based on the surveillance, epidemiology, and end results (SEER) database, 1980-2017. Am J Hematol 96:650–658. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fajh.26156\nKeegan TH, Ries LA, Barr RD, Geiger MA, Vollmer Dahlke D, Pollock BH, Bleyer WA (2016) Comparison of cancer survival trends in the United States of adolescents and young adults with those in children and older adults. Cancer 122:1009–1016. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fcncr.29869\nSeftel MD, Neuberg D, Zhang MJ et al (2016) Pediatric inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission. Am J Hematol 91:322–329. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fajh.24285\nMcNeer JL, Bleyer A (2018) Acute lymphoblastic leukemia and lymphoblastic lymphoma in adolescents and young adults. Pediatr Blood Cancer 65:e26989. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fpbc.26989\nRytting ME, Jabbour EJ, O’Brien SM, Kantarjian HM (2017) Acute lymphoblastic leukemia in adolescents and young adults. Cancer 123:2398–2403. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fcncr.30624\nBoissel N, Baruchel A (2018) Acute lymphoblastic leukemia in adolescent and young adults: treat as adults or as children? Blood 132:351–361. https:\u002F\u002Fdoi.org\u002F10.1182\u002Fblood-2018-02-778530\nSiegel SE, Stock W, Johnson RH, Advani A, Muffly L (2018) Pediatric-inspired treatment regimens for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: a review. JAMA Oncol 4:725–734. https:\u002F\u002Fdoi.org\u002F10.1001\u002Fjamaoncol.2017.5305\nOlivier-Gougenheim L, Arfeuille C, Suciu S et al (2020) Pediatric randomized trial EORTC CLG 58951: outcome for adolescent population with acute lymphoblastic leukemia. Hematol Oncol 38:763–772. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fhon.2791\nAldoss I, Douer D (2020) How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood 135:987–995. https:\u002F\u002Fdoi.org\u002F10.1182\u002Fblood.2019002477\nKoprivnikar J, McCloskey J, Faderl S (2017) Safety, efficacy, and clinical utility of asparaginase in the treatment of adult patients with acute lymphoblastic leukemia. Onco Targets Ther 10:1413–1422. https:\u002F\u002Fdoi.org\u002F10.2147\u002FOTT.S106810\nChrist TN, Stock W, Knoebel RW (2018) Incidence of asparaginase-related hepatotoxicity, pancreatitis, and thrombotic events in adults with acute lymphoblastic leukemia treated with a pediatric-inspired regimen. J Oncol Pharm Prac 24:299–308. https:\u002F\u002Fdoi.org\u002F10.1177\u002F1078155217701291\nSmith AW, Schwartz SM, Hamilton LC, Wu XC, Schwartz SM, Kato I, Cress R, Harlan L (2019) AYA HOPE Study Collaborative Group. Understanding care and outcomes in adolescents and young adult with cancer: a review of the AYA HOPE study. Pediatr Blood Cancer 66(1):e27486. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fpbc.27486\nQuiroz E, Venkateswaran AR, Nelson R, Aldoss I, Pullarkat V, Rego E, Marcucci G, Douer D (2022) Immunophenotype of acute lymphoblastic leukemia in minorities- analysis from the SEER database. Hematol Oncol 40:105–110. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fhon.2945\nToft N, Birgens H, Abrahamsson J et al (2018) Results of NOPHO ALL 2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia. Leukemia 32:606–615. https:\u002F\u002Fdoi.org\u002F10.1038\u002Fleu.2017.265\nStock W, Luger SM, Advani AS et al (2019) A pediatric regimen for old adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood 133:1548–1559. https:\u002F\u002Fdoi.org\u002F10.1182\u002Fblood-2018-10-881961\nShort NJ, Jabbour E (2017) Minimal residual disease in acute lymphoblastic leukemia: how to recognize and treat it. Curr Oncol Rep 19:6–8. https:\u002F\u002Fdoi.org\u002F10.1007\u002Fs11912-017-0565-x\nShort NJ, Jabbour E, Albitar M et al (2019) Recommendations for the assessment and management of measurable residual disease in adults with acute lymphoblastic leukemia: a consensus of North American experts. Am J Hematol 94:257–265. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fajh.25338\nBerry DA, Zhou S, Higley H et al (2017) Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis. JAMA. Oncol 3:e170580. https:\u002F\u002Fdoi.org\u002F10.1001\u002Fjamaoncol.2017.0580\nBassan R, Intermesoli T, Scattolin A et al (2017) Minimal residual disease assessment and risk-based therapy in acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk 17S:S2–S9. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.clml.2017.02.019\nTesti AM, Canichella M, Vitale A et al (2021) Adolescent and young adult acute lymphoblastic leukemia. Final results of the phase II pediatric-like GIMEMA LAL-1308 trial. Am J Hematol 96:292–301. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fajh.26066\nWhite VM, Skaczkowski G, Pinkerton R et al (2018) Clinical management of Australian adolescents and young adults with acute lymphoblastic and myeloid leukemia: a national population-based study. Pediatr Blood Cancer 65:e27349. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fpbc.27349\nDeAngelo DJ, Stevenson KE, Dahlberg SE et al (2015) Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia 29:526–534. https:\u002F\u002Fdoi.org\u002F10.1038\u002Fleu.2014.229\nRibera JM, Morgades M, Montesinos P et al (2020) A pediatric regimen for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: results of the ALLRE08 PETHEMA trial. Cancer Med 9:2317–2329. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fcam4.2814\nHanbali A, Kotb A, Fakih RE et al (2021) Improved survival in adolescents and young adults (AYA) patients aged 14-55 years with acute lymphoblastic leukemia using pediatric-inspired protocol - a retrospective analysis of a real-world experience in 79 of patients treated at a national tertiary care referral center. Leuk Res Rep 16:100270. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.lrr.2021\nRajendra A, Jain H, Bonda VNA et al (2021) Outcomes and prognostic factors in adolescents and young adults with ALL treated with a modified BFM-90 protocol. Blood Adv 5:1178–1193. https:\u002F\u002Fdoi.org\u002F10.1182\u002Fbloodadvances.2020003526\nCrespo-Solis E, Espinosa-Bautista K, Alvarado-Ibarra M et al (2018) Survival analysis of adult patients with ALL in Mexico City: first report from the Acute Leukemia Workgroup (ALWG) (GTLA). Cancer Med 7:2423–2433. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fcam4.1513\nBassan R, Pavoni C, Intermesoli T et al (2020) Updated risk-oriented strategy for acute lymphoblastic leukemia in adult patients 18–65 years: NILG ALL 10\u002F07. Blood Cancer J 10:119. https:\u002F\u002Fdoi.org\u002F10.1038\u002Fs41408-020-00383-2\nViardot A, Locatelli F, Stieglmaier J, Zaman F, Jabbour E (2020) Concepts in immuno-oncology: tackling B cell malignancies with CD19-directed bispecific T cell engager therapies. Ann Hematol 99:2215–2229. https:\u002F\u002Fdoi.org\u002F10.1007\u002Fs00277-020-04221-0\nSaygin C, Cannova J, Stock W, Muffly L (2022) Measurable residual disease in acute lymphoblastic leukemia: methods and clinical context in adult patients. Haematologica 107:2783–2793. https:\u002F\u002Fdoi.org\u002F10.3324\u002Fhaematol.2022.280638\nKotrova M, Koopmann J, Trautmann H et al (2022) Prognostic value of low-level MRD in adult acute lymphoblastic leukemia detected by low- and high-throughput methods. Blood Adv 6:3006–3010. https:\u002F\u002Fdoi.org\u002F10.1182\u002Fbloodadvances.2021006727\nLadetto M, Bruggemann M, Monitillo L et al (2014) Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders. 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