臨床検査54巻3号

2010年03月発行

今月の主題 骨髄増殖性疾患 総論

骨髄増殖性疾患の概念

著者： 金倉譲¹

所属機関： ¹大阪大学大学院医学系研究科血液・腫瘍内科

ページ範囲：P.227 - P.233

　骨髄増殖性疾患は，造血幹細胞レベルの細胞に遺伝子異常が起こり，分化能を有する複数の系統の骨髄系細胞がクローナルに過剰増殖する疾患群であり，しばしば病型間の移行もみられる．高齢者に多く発症し，経過は緩徐であるが，一部の症例は急性骨髄性白血病へと移行する．その原因のほとんどは染色体転座や点突然変異などによるチロシンキナーゼの恒常的活性化であり，真性多血症のほとんどの症例，本態性血小板血症，原発性骨髄線維症の約半数の症例でJAK2の，慢性骨髄性白血病ではBCR-ABLの活性化変異が認められる．

参考文献

1) Dameshek W：Some speculations on the myeloproliferative syndromes. Blood　6：372-375, 1951

2) Jaffe ES, Harris NL, Stein H, et al(ed)：Pathology and Genetics：Tumours of Haematopoietic and Lymphoid Tissues, Intl Agency for Research on Cancer, Lyon, pp15-42, 2003

3) Swerdlow SH, Campo E, Harris NL, et al(ed)：WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed, Intl Agency for Research on Cancer, Lyon, pp31-73, 2008

4) Adamson JW, Fialkow PJ, Murphy S, et al：Polycythemia vera：stem-cell and probable clonal origin of the disease. N Engl J Med　295：913-916, 1976

5) Dai CH, Krantz SB, Means RT Jr, et al：Polycythemia vera blood burst-forming units-erythroid are hypersensitive to interleukin-3. J Clin Invest　87：391-396, 1991

：studies in an improved serum-free medium. Blood　83：99-9112, 1994

7) Levine RL, Pardanani A, Tefferi A, et al：Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer　7：673-683, 2007

8) Patnaik MM, Tefferi A：Molecular diagnosis of myeloproliferative neoplasms. Expert Rev Mol Diagn　9：481-492, 2009

9) Tiedt R, Hao-Shen H, Sobas MA, et al：Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice. Blood　111：3931-3940, 2008

10) Xing S, Wanting TH, Zhao W, et al：Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice. Blood　111：5109-5117, 2008

11) Campbell PJ, Baxter EJ, Beer PA, et al：Mutation of JAK2 in the myeloproliferative disorders：timing, clonality studies, cytogenetic associations, and role in leukemic transformation. Blood　108：3548-3555, 2006

12) Kralovics R, Teo SS, Li S, et al：Acquisition of the V617F mutation of JAK2 is a late genetic event in a subset of patients with myeloproliferative disorders. Blood　108：1377-1380, 2006

13) Delhommeau F, Dupont S, Della Valle V, et al：Mutation in TET2 in myeloid cancers. N Engl J Med　360：2289-2301, 2009

14) Langemeijer SM, Kuiper RP, Berends M, et al：Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet　41：838-842, 2009

15) Jost E, do O N, Dahl E, et al：Epigenetic alterations complement mutation of JAK2 tyrosine kinase in patients with BCR/ABL-negative myeloproliferative disorders. Leukemia　21：505-510, 2007

16) Grand FH, Hidalgo-Curtis CE, Ernst T, et al：Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood　113：6182-6192, 2009

17) Levine RL, Gilliland DG：Myeloproliferative disorders. Blood　112：2190-2198, 2008

18) Jones AV, Chase A, Silver RT, et al：JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nat Genet　41：446-449, 2009

19) Olcaydu D, Harutyunyan A, Jäger R, et al：A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat Genet　41：450-454, 2009

20) Kilpivaara O, Mukherjee S, Schram AM, et al：A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat Genet　41：455-459, 2009