慢性髓性白血病原始细胞转化中遗传异常的克隆进化及其临床意义。

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia.

机构信息

Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

出版信息

Nat Commun. 2021 May 14;12(1):2833. doi: 10.1038/s41467-021-23097-w.

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.

急变期（BC）预示着慢性髓性白血病（CML）患者预后不良。虽然其他遗传改变在 BC 中起核心作用，但这些改变的全貌及其预后影响仍难以捉摸。在这里，我们使用外显子组和靶向测序，对 216 例 CML 患者的 136 例 BC 和 148 例慢性期（CP）样本进行了全面的基因异常研究。在 136 例 BC 患者中，有 126 例（92.6%）发现了一种或多种基因异常，包括 RUNX1-ETS2 融合和 NBEAL2 突变。从 CP 到 BC 的转变过程中，遗传改变的数量增加，而酪氨酸激酶抑制剂（TKI）则显著抑制了这种增加。BC 的谱系和先前使用 TKI 与不同的分子特征相关。值得注意的是，遗传改变而不是临床变量有助于更好地预测 BC 的预后。总之，基因异常有助于预测临床结果，并指导 CML 的临床决策。