Emergence of clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph-) cells in chronic myeloid leukemia (CML) patients during the treatment with tyrosine kinase inhibitors (TKIs) is an interesting phenomenon. Although previous studies revealed some potential impact of CCA/Ph- on CML patients’ outcome, clinical significance of CCA/Ph- in CML patients remains to be further elucidated. We retrospectively reviewed the patients with CML evaluated at Genoptix Medical Laboratory in Carlsbad, California from 2005 to 2015. Twenty-four CML patients with CCA/Ph- cells were identified. These include 18 patients with single chromosomal abnormality, 4 patients with double chromosomal abnormalities, and two patients with complex cytogenetic abnormalities. In addition to trisomy 8 and monosomy 7, we identified that 20q- was also a common abnormality in CCA/Ph- cells. Most of the patients with CCA/Ph- cells demonstrated no significant dysplasia or increased blasts with two exceptions: one patient with persistent 7q- exhibiting mild dysmegakaryopoiesis, suggestive of an early evolving myelodysplastic syndrome, and another patient with complex cytogenetic abnormalities who developed acute myeloid leukemia after gained MLL amplification. One patient with complex cytogenetic abnormalities showed optimal response to TKI treatment, no overt dysplasia, and no disease progression during almost 4-years of follow-up. More interestingly, FISH tests could identify more cases with double chromosomal abnormalities and these cases showed suboptimal responses to TKI treatments. Our observation indicates that 20q- was also a common abnormality in CCA/Ph- cells, further FISH tests revealed additional CCA/Ph-, and the majority of CML patients with two or more chromosomal abnormalities in Ph- cells showed inferior response to TKI treatments. The results of our study suggest that CML cases with CCA/Ph- may represent a group of patients with heterogeneous genetic alterations.

酪氨酸激酶抑制剂（TKIs）治疗期间，慢性髓细胞性白血病（CML）患者的费城染色体阴性（CCA / Ph-）细胞中出现克隆染色体异常是一种有趣的现象。尽管先前的研究表明CCA / Ph-对CML患者的预后有潜在影响，但是CCA / Ph-在CML患者中的临床意义仍有待进一步阐明。我们回顾性研究了2005年至2015年在加利福尼亚州卡尔斯巴德的Genoptix医学实验室评估的CML患者。确定了24例CCA / Ph-细胞CML患者。其中包括18位单染色体异常患者，4位双染色体异常患者和2位复杂的细胞遗传学异常患者。除了8三体和7三体，我们发现20q-也是CCA / Ph-细胞中的常见异常。大多数具有CCA / Ph-细胞的患者均未显示出明显的发育异常或胚泡增加，但有两个例外：一名持续7q表现为轻度异常核型造血的患者，提示早期发展为骨髓增生异常综合症，另一名患有复杂细胞遗传异常的患者发展为急性髓样得了白血病MLL扩增。一名具有复杂细胞遗传学异常的患者在近4年的随访中显示出对TKI治疗的最佳反应，没有明显的发育异常，也没有疾病进展。更有趣的是，FISH测试可以发现更多具有双重染色体异常的病例，这些病例显示出对TKI治疗的反应欠佳。我们的观察结果表明，20q-也是CCA / Ph-细胞的常见异常，进一步的FISH测试显示了额外的CCA / Ph-，大多数CML患者在Ph-细胞中有两个或多个染色体异常显示出对TKI治疗的反应较差。我们的研究结果表明，带有CCA / Ph-的CML病例可能代表了一组具有异质遗传变异的患者。