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  • Title: Clinical implications of clonal chromosomal abnormalities in Philadelphia negative cells in CML patients after treated with tyrosine kinase inhibitors.
    Author: Ni H, Sun X, Xu Y, Lyle D, Petersen P, Zhao X, Drum H, You B, Liu D, Liu C, Jiang JG.
    Journal: Cancer Genet; 2019 Oct; 238():44-49. PubMed ID: 31425925.
    Abstract:
    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.
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