SNP chip data of CML, resistant with tyrosine kinase inhibitor

To elucidate whether tyrosine kinase inhibitor (TKI) resistance in CML is associated with characteristic genomic alterations, we analyzed DNA samples from 45 TKI resistant CML patients with 250K single nucleotide polymorphism (SNP) arrays. From 20 patients, matched serial samples of pre-treatment and TKI resistance time points were available. 11 of the 45 TKI resistant patients had mutations of BCR-ABL1, including two T315I mutations. Besides known TKI resistance associated genomic lesions such as duplication of the BCR-ABL1 gene (n=8) and trisomy 8 (n=3), recurrent submicroscopic alterations including acquired uniparental disomy were detectable on chromosomes 1, 8, 9, 17, 19 and 22. On chromosome 22, newly acquired and recurrent deletions of the IGLC1 locus were detected in three patients, who had previously presented with lymphoid or myeloid blast crisis. This may support a hypothesis of TKI induced selection of subclones differentiating into immature B-cell progenitors as a mechanism of disease progression and evasion of TKI sensitivity. Keywords: SNP-chip To identify oncogenic lesions in CML, we performed a genome-wide analysis of primary CML samples using high-density SNP arrays (Affymetrix GeneChip).

为阐明慢性髓系白血病（Chronic Myeloid Leukemia, CML）中的酪氨酸激酶抑制剂（TKI）耐药是否与特征性基因组改变相关，我们采用250K单核苷酸多态性（Single Nucleotide Polymorphism, SNP）芯片对45例TKI耐药的CML患者的DNA样本开展了分析。其中20例患者可获取治疗前及TKI耐药阶段的配对系列样本。45例TKI耐药患者中，11例存在BCR-ABL1突变，其中包括2例T315I突变。除已知的与TKI耐药相关的基因组异常（如BCR-ABL1基因拷贝数扩增（n=8）及8号染色体三体（n=3））外，在1、8、9、17、19及22号染色体上还检测到复发性亚显微改变，包括获得性单亲二体。在22号染色体上，3例曾出现淋巴系或髓系急变的患者中检测到新发且复发性的IGLC1基因座缺失。本研究结果可为下述假说提供支撑：TKI诱导筛选出分化为未成熟B细胞前体的亚克隆，该过程是疾病进展及逃逸TKI敏感性的潜在机制。关键词：SNP芯片。为鉴定CML中的致癌性病变，我们采用高密度SNP芯片（Affymetrix GeneChip）对原发性CML样本进行了全基因组分析。