JAK2V617F homozygosity drives a phenotypic switch in myeloproliferative neoplasms, but is insufficient to sustain disease

Tuna, 2009, Uniparental disomy in cancer., Trends Mol Med, 15, 120, 10.1016/j.molmed.2009.01.005 Kralovics, 2002, Acquired uniparental disomy of chromosome 9p is a frequent stem cell defect in polycythemia vera., Exp Hematol, 30, 229, 10.1016/S0301-472X(01)00789-5 Baxter, 2005, Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders., Lancet, 365, 1054, 10.1016/S0140-6736(05)71142-9 James, 2005, A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera., Nature, 434, 1144, 10.1038/nature03546 Levine, 2005, Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis., Cancer Cell, 7, 387, 10.1016/j.ccr.2005.03.023 Kralovics, 2005, A gain-of-function mutation of Jak2 in myeloproliferative disorders., N Engl J Med, 352, 1779, 10.1056/NEJMoa051113 Raghavan, 2005, Genome-wide single nucleotide polymorphism analysis reveals frequent partial uniparental disomy due to somatic recombination in acute myeloid leukemias., Cancer Res, 65, 375, 10.1158/0008-5472.375.65.2 Dunbar, 2008, 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies., Cancer Res, 68, 10349, 10.1158/0008-5472.CAN-08-2754 Szpurka, 2009, UPD1p indicates the presence of MPL W515L mutation in RARS-T, a mechanism analogous to UPD9p and JAK2 V617F mutation., Leukemia, 23, 610, 10.1038/leu.2008.249 Vainchenker, 2011, New mutations and pathogenesis of myeloproliferative neoplasms., Blood, 118, 1723, 10.1182/blood-2011-02-292102 Godfrey, 2012, JAK2V617F homozygosity arises commonly and recurrently in PV and ET, but PV is characterized by expansion of a dominant homozygous subclone., Blood, 120, 2704, 10.1182/blood-2012-05-431791 Chen, 2010, Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling., Cancer Cell, 18, 524, 10.1016/j.ccr.2010.10.013 Li, 2011, Mouse models of myeloproliferative neoplasms: JAK of all grades., Dis Model Mech, 4, 311, 10.1242/dmm.006817 Akada, 2010, Conditional expression of heterozygous or homozygous Jak2V617F from its endogenous promoter induces a polycythemia vera-like disease., Blood, 115, 3589, 10.1182/blood-2009-04-215848 Mullally, 2010, Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells., Cancer Cell, 17, 584, 10.1016/j.ccr.2010.05.015 Marty, 2010, Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice., Blood, 116, 783, 10.1182/blood-2009-12-257063 Li, 2010, JAK2 V617F impairs hematopoietic stem cell function in a conditional knock-in mouse model of JAK2 V617F-positive essential thrombocythemia., Blood, 116, 1528, 10.1182/blood-2009-12-259747 Liu, 2011, Stella-Cre mice are highly efficient Cre deleters., Genesis, 49, 689, 10.1002/dvg.20741 Vannucchi, 2007, Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden., Leukemia, 21, 1952, 10.1038/sj.leu.2404854 Passamonti, 2010, A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications., Leukemia, 24, 1574, 10.1038/leu.2010.148 Godfrey, 2013, Clonal analyses reveal associations of JAK2V617F homozygosity with hematologic features, age and gender in polycythemia vera and essential thrombocythemia., Haematologica, 98, 718, 10.3324/haematol.2012.079129 Dupont, 2007, The JAK2 617V>F mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera., Blood, 110, 1013, 10.1182/blood-2006-10-054940 Passamonti, 2006, Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders., Blood, 107, 3676, 10.1182/blood-2005-09-3826 Hobbs, 2013, JAK2V617F leads to intrinsic changes in platelet formation and reactivity in a knock-in mouse model of essential thrombocythemia., Blood, 122, 3787, 10.1182/blood-2013-06-501452 Zhang, 2003, Role of Ras signaling in erythroid differentiation of mouse fetal liver cells: functional analysis by a flow cytometry-based novel culture system., Blood, 102, 3938, 10.1182/blood-2003-05-1479 Plo, 2008, JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders., Blood, 112, 1402, 10.1182/blood-2008-01-134114 Kent, 2009, Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential., Blood, 113, 6342, 10.1182/blood-2008-12-192054 Dykstra, 2007, Long-term propagation of distinct hematopoietic differentiation programs in vivo., Cell Stem Cell, 1, 218, 10.1016/j.stem.2007.05.015 Kent, 2013, Self-renewal of single mouse hematopoietic stem cells is reduced by JAK2V617F without compromising progenitor cell expansion., PLoS Biol, 11, e1001576, 10.1371/journal.pbio.1001576 Kawamata, 2008, Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray., Exp Hematol, 36, 1471, 10.1016/j.exphem.2008.06.006 Van Etten, 2011, The Ph-positive and Ph-negative myeloproliferative neoplasms: some topical pre-clinical and clinical issues., Haematologica, 96, 590, 10.3324/haematol.2010.035675 Lippert, 2006, The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera., Blood, 108, 1865, 10.1182/blood-2006-01-013540 Scott, 2006, Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia., Blood, 108, 2435, 10.1182/blood-2006-04-018259 Scott, 2007, JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis., N Engl J Med, 356, 459, 10.1056/NEJMoa065202 Passamonti, 2011, Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations., Blood, 117, 2813, 10.1182/blood-2010-11-316810 Tiedt, 2008, Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice., Blood, 111, 3931, 10.1182/blood-2007-08-107748 Dahabreh, 2009, Is JAK2 V617F mutation more than a diagnostic index? A meta-analysis of clinical outcomes in essential thrombocythemia., Leuk Res, 33, 67, 10.1016/j.leukres.2008.06.006 Harrison, 2005, Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia., N Engl J Med, 353, 33, 10.1056/NEJMoa043800 Di Nisio, 2007, The haematocrit and platelet target in polycythemia vera., Br J Haematol, 136, 249, 10.1111/j.1365-2141.2006.06430.x Richmond, 2005, Turning cells red: signal transduction mediated by erythropoietin., Trends Cell Biol, 15, 146, 10.1016/j.tcb.2005.01.007 Koury, 1990, Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells., Science, 248, 378, 10.1126/science.2326648 Fang, 2007, EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts., Blood, 110, 2361, 10.1182/blood-2006-12-063503 Sathyanarayana, 2008, EPO receptor circuits for primary erythroblast survival., Blood, 111, 5390, 10.1182/blood-2007-10-119743 Chen, 2012, Janus kinase deregulation in leukemia and lymphoma., Immunity, 36, 529, 10.1016/j.immuni.2012.03.017 Panova-Noeva, 2011, Platelet-induced thrombin generation by the calibrated automated thrombogram assay is increased in patients with essential thrombocythemia and polycythemia vera [published correction appears in Am J Hematol. 2011;86(5):466]., Am J Hematol, 86, 337, 10.1002/ajh.21974 Mullally, 2013, Depletion of Jak2V617F myeloproliferative neoplasm-propagating stem cells by interferon-α in a murine model of polycythemia vera., Blood, 121, 3692, 10.1182/blood-2012-05-432989 Hasan, 2013, JAK2V617F expression in mice amplifies early hematopoietic cells and gives them a competitive advantage that is hampered by IFNα., Blood, 122, 1464, 10.1182/blood-2013-04-498956 Xu, 2007, JAK2(V617F): Prevalence in a large Chinese hospital population., Blood, 109, 339, 10.1182/blood-2006-03-009472 Moliterno, 2008, Phenotypic variability within the JAK2 V617F-positive MPD: roles of progenitor cell and neutrophil allele burdens., Exp Hematol, 36, 1480, 10.1016/j.exphem.2008.05.006 Jamieson, 2006, The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation., Proc Natl Acad Sci U S A, 103, 6224, 10.1073/pnas.0601462103 James, 2008, The hematopoietic stem cell compartment of JAK2V617F-positive myeloproliferative disorders is a reflection of disease heterogeneity., Blood, 112, 2429, 10.1182/blood-2008-02-137877 Ishii, 2007, Behavior of CD34+ cells isolated from patients with polycythemia vera in NOD/SCID mice., Exp Hematol, 35, 1633, 10.1016/j.exphem.2007.07.005 Jamieson, 2004, Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML., N Engl J Med, 351, 657, 10.1056/NEJMoa040258 Schemionek, 2010, BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells., Blood, 115, 3185, 10.1182/blood-2009-04-215376 Reynaud, 2011, IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development., Cancer Cell, 20, 661, 10.1016/j.ccr.2011.10.012 Gorgoulis, 2010, Oncogene-induced senescence: the bright and dark side of the response., Curr Opin Cell Biol, 22, 816, 10.1016/j.ceb.2010.07.013