Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin

Blood - Tập 103 - Trang 4198-4200 - 2004
Jianmin Ding, Hirokazu Komatsu, Atsushi Wakita, Miyuki Kato-Uranishi, Masato Ito, Atsushi Satoh, Kazuya Tsuboi, Masakazu Nitta, Hiroshi Miyazaki, Shinsuke Iida, Ryuzo Ueda

Tóm tắt

Abstract One Japanese pedigree of familial essential thrombocythemia (FET) inherited in an autosomal-dominant manner is presented. A unique point mutation, serine 505 to asparagine 505 (Ser505Asn), was identified in the transmembrane domain of the c-MPL gene in all of the 8 members with thrombocythemia, but in none of the other 8 unaffected members in this FET family. The Ba/F3 cells expressing the mutant Asn505 acquired interleukin 3 (IL-3)-independent survival capacity, whereas those expressing wild-type Ser505 did not. The autonomous phosphorylation of Mek1/2 and Stat5b was observed in the mutant Ba/F3 cells in the absence of IL-3. The former was also found in platelets derived from the affected individual in the absence of thrombopoietin. These results show that the Asn505 is an activating mutation with respect to the intracellular signaling and survival of the cells. This is the first report of FET deriving from a dominant-positive activating mutation of the c-MPL gene. (Blood. 2004;103: 4198-4200)

Tài liệu tham khảo

Kondo T, Okabe M, Sanada M, et al. Familial essential thrombocythemia associated with one-base deletion in the 5′-untranslated region of the thrombopoietin gene. Blood.1998;92: 1091-1096. Ghilardi N, Wiestner A, Kikuchi M, Ohsaka A, Skoda RC. Hereditary thrombocythaemia in a Japanese family is caused by a novel point mutation in the thrombopoietin gene. Br J Haematol.1999;107: 310-316. Ihara K, Ishii E, Eguchi M, et al. Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia. Proc Natl Acad Sci U S A.1999;96: 3132-3136. Ballmaier M, Germeshausen M, Schulze H, et al. c-mpl mutations are the cause of congenital amegakaryocytic throbocytopenia. Blood.2001; 97: 139-146. Tonelli R, Scardovi AL, Pession A, et al. Compound heterozygosity for two different amino-acid substitution mutations in the thrombopoietin receptor (c-mpl gene) in congenital amegakaryocytic thrombocytopenia (CAMT). Hum Genet.2000;107: 225-233. van den Oudenrijn S, Bruin M, Folman CC, et al. Mutations in the thrombopoietin receptor, Mpl, in children with congenital amegakaryocytic thrombocytopenia. Br J Haematol.2000;110: 441-448. Migliazza A, Bosch F, Komatsu H, et al. Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia. Blood.2001;97: 2098-2104. Kato M, Iida S, Komatsu H, Ueda R. Lack of Ku80 alteration in multiple myeloma. Jpn J Cancer Res.2002;93: 359-362. Kitayama H, Kanakura Y, Furitsu T, et al. Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines. Blood.1995;85: 790-798. Miyakawa Y, Oda A, Druker BJ, et al. Recombinant thrombopoietin induces rapid protein tyrosine phosphorylation of Janus kinase 2 and Shc in human blood platelets. Blood.1995;86: 23-27. Michiels JJ, Juvonen E. Proposal for revised diagnostic criteria of essential thrombocythemia and polycythemia vera by the thrombocythemia vera study group. Semin Thromb Hemost.1997; 23: 339-347. Abe M, Suzuki K, Inagaki O, Sassa S, Shikama H. A novel MPL point mutation resulting in thrombopoietin-independent activation. Leukemia.2002;16: 1500-1506. Weiner DB, Liu J, Cohen JA, Villiams WY, Greene MI. A point mutation in the neu oncogene mimics ligand induction of receptor aggregation. Nature.1989;339: 230-231. Onishi M, Mui AL, Morikawa Y, et al. Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer. Blood.1996;88: 1399-1406. Horikawa Y, Matsumura I, Hashimoto K, et al. Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia. Blood.1997;90: 4031-4038. Taksin AL, Couedic JP, Dusanter-Fourt I, et al. Autonomous megakaryocyte growth in essential thrombocythemia and idiopathic myelofibrosis is not related to a c-mpl mutation or to an autocrine stimulation by Mpl-L. Blood.1999;93: 125-139. AQ0: Changed the short running head so it would have fewer than 50 characters, per journal limit.