CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia
CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia
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DOI：
10.1182/blood-2010-06-292433
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发表时间：
2011-05-26
期刊：
影响因子：
20.3
通讯作者：
Maciejewski, Jaroslaw P.
中科院分区：
文献类型：
--
作者：
Makishima, Hideki;Jankowska, Anna M.;Maciejewski, Jaroslaw P.
慢性粒细胞白血病(CML)向加速期(AP)和急变期(BP)的进展是由于继发性分子事件和额外的细胞遗传学异常。基于对骨髓异常增生/骨髓增生性肿瘤中JAK2、CBL、CBLB、TET2、ASXL1和IDH1/2突变的检测，我们推测它们也可能与CML的进展有关。我们对54例CML患者(14例慢性期，14例AP，20例髓系，6例非髓系BP)进行了基因突变筛查。我们在AP中发现了1个CBLB和2个TET2突变，在髓系BP中发现了1个CBL、1个CBLB、4个TET2、2个ASXL1和2个IDH家族突变。但在慢性期未发现这些突变。未发现JAK2V617F突变病例。在2例患者中，发现TET2突变伴随CBLB突变。单核苷酸多态芯片检测发现，AP和BP在染色体5q、8q、11p和17p上存在单亲二体，但不涉及4q24(TET2)和11q23(CBL)。染色体17q11.2和21q22.12上的微缺失分别涉及肿瘤相关基因NF1和RUNX1。我们的结果表明，晚期CML可发生CBL家族、TET2、ASXL1和IDH家族突变和额外的隐匿性核型异常。(血。2011；117(21)：E198-E206)
Progression of chronic myelogenous leukemia (CML) to accelerated (AP) and blast phase (BP) is because of secondary molecular events, as well as additional cytogenetic abnormalities. On the basis of the detection of JAK2, CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations in myelodysplastic/myeloproliferative neoplasms, we hypothesized that they may also contribute to progression in CML. We screened these genes for mutations in 54 cases with CML(14 with chronic phase, 14 with AP, 20 with myeloid, and 6 with nonmyeloid BP). We identified 1 CBLB and 2 TET2 mutations in AP, and 1 CBL, 1 CBLB, 4 TET2, 2 ASXL1, and 2 IDH family mutations in myeloid BP. However, none of these mutations were found in chronic phase. No cases with JAK2V617F mutations were found. In 2 cases, TET2 mutations were found concomitant with CBLB mutations. By single nucleotide polymorphism arrays, uniparental disomy on chromosome 5q, 8q, 11p, and 17p was found in AP and BP but not involving 4q24 (TET2) or 11q23 (CBL). Microdeletions on chromosomes 17q11.2 and 21q22.12 involved tumor associated genes NF1 and RUNX1, respectively. Our results indicate that CBL family, TET2, ASXL1, and IDH family mutations and additional cryptic karyotypic abnormalities can occur in advanced phase CML. (Blood. 2011; 117(21): e198-e206)