Genomic profiling of Imatinib resistance in CD34+ cell populations from chronic myeloid leukaemia patients using Agilent-014698 Whole Human Genome 105K microarrays.

To ascertain genomic alterations associated with Imatinib resistance in chronic myeloid leukaemia, we performed high resolution genomic analysis of CD34+ cells from 25 Imatinib (IM) resistant and 11 responders CML patients. Using patients' T-cells as reference, we found significant association between number of acquired cryptic copy number alterations (CNA) and disease phase (p=0.036) or loss of IM response for patients diagnosed in chronic phase (CP) (p=0.04). Recurrent cryptic losses were identified on chromosomes 7, 12 and 13. On chromosome 7, recurrent deletions of the IKZF1 locus were detected, for the first time, in four patients in CP. Patients suffering from chronic myeloid leukaemia were compared using CD34+ cells and T cells as reference and hybridized on Agilent-014698 Whole Human Genome 105K microarrays.

为明确与慢性髓性白血病（chronic myeloid leukaemia, CML）伊马替尼（Imatinib, IM）耐药相关的基因组改变，本研究对25例伊马替尼耐药及11例伊马替尼应答良好的慢性髓性白血病患者的CD34+细胞（CD34+ cells）开展了高分辨率基因组分析。以患者自身T细胞作为参照，我们发现获得性隐秘性拷贝数变异（cryptic copy number alterations, CNA）的数量与疾病分期（p=0.036）存在显著关联；对于确诊时处于慢性期（chronic phase, CP）的患者，该变异数量还与伊马替尼应答丧失显著相关（p=0.04）。研究团队在7号、12号及13号染色体上鉴定出复发性隐秘缺失；其中在7号染色体上，本研究首次在4例慢性期患者中检测到IKZF1基因座的复发性缺失。本研究以慢性髓性白血病患者的CD34+细胞与T细胞作为参照，将样本在安捷伦（Agilent）-014698全人类基因组105K微阵列上完成杂交，以实现样本间的比较分析。