Ahuja H G, Popplewell L, Tcheurekdjian L, Slovak M L
Roswell Park Cancer Institute, Department of Medicine, Buffalo, NY, USA.
Genes Chromosomes Cancer. 2001 Apr;30(4):410-5. doi: 10.1002/1098-2264(2001)9999:9999<::aid-gcc1108>3.0.co;2-9.
The role of the BCR-ABL fusion gene in the pathogenesis of the chronic phase of chronic myelogenous leukemia (CML) has been well established. Several additional genetic changes have been reported to occur, at varying frequencies, during disease progression to "accelerated" and "blast crisis" phases. The NUP98 gene localized to chromosome band 11p15 has been found at the breakpoints of several distinct chromosomal translocations in patients with both de novo and therapy-related myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). Using combined cytogenetic and molecular analyses, we have found rearrangements of the NUP98 gene in the leukemic cells of two patients with Philadelphia chromosome-positive CML, during disease evolution. As expected, analysis of the t(7;11)(p15;p15) from one of the patients showed an in-frame NUP98-HOXA9 fusion. The fusion points were similar to previously reported NUP98-HOXA9 fusion points from patients with MDS/AML. Our results indicate that the NUP98 gene is an additional, albeit infrequent, genetic target during clonal evolution of CML.
BCR-ABL融合基因在慢性粒细胞白血病（CML）慢性期发病机制中的作用已得到充分证实。据报道，在疾病进展至“加速期”和“急变期”的过程中，还会出现一些频率各异的其他基因变化。定位于染色体11p15带的NUP98基因，在初发和治疗相关的骨髓增生异常综合征（MDS）及急性髓细胞白血病（AML）患者的几种不同染色体易位断点处均有发现。通过联合细胞遗传学和分子分析，我们发现在疾病进展过程中，两名费城染色体阳性CML患者的白血病细胞中存在NUP98基因重排。正如预期的那样，对其中一名患者的t(7;11)(p15;p15)分析显示存在框内NUP98-HOXA9融合。融合点与先前报道的MDS/AML患者的NUP98-HOXA9融合点相似。我们的结果表明，NUP98基因是CML克隆进化过程中另一个虽不常见但存在的基因靶点。
