Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210.
Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
Proc Natl Acad Sci U S A. 2021 Mar 16;118(11). doi: 10.1073/pnas.2101566118.
Despite advances that have improved the treatment of chronic myeloid leukemia (CML) patients in chronic phase, the mechanisms of the transition from chronic phase CML to blast crisis (BC) are not fully understood. Considering the key role of miR-15/16 loci in the pathogenesis of myeloid and lymphocytic leukemia, here we aimed to correlate the expression of miR-15a/16 and miR-15b/16 to progression of CML from chronic phase to BC. We analyzed the expression of the two miR-15/16 clusters in 17 CML patients in chronic phase and 22 patients in BC and in 11 paired chronic phase and BC CML patients. BC CMLs show a significant reduction of the expression of miR-15a/-15b/16 compared to CMLs in chronic phase. Moreover, BC CMLs showed an overexpression of miR-15/16 direct targets such as Bmi-1, ROR1, and Bcl-2 compared to CMLs in chronic phase. This study highlights the loss of both miR-15/16 clusters as a potential oncogenic driver in the transition from chronic phase to BC in CML patients.
尽管在慢性髓系白血病（CML）慢性期患者的治疗方面取得了进展，但从慢性期 CML 向急变期（BC）转变的机制仍不完全清楚。鉴于 miR-15/16 基因座在髓系和淋巴细胞白血病发病机制中的关键作用，我们旨在将 miR-15a/16 和 miR-15b/16 的表达与 CML 从慢性期向 BC 的进展相关联。我们分析了 17 例慢性期 CML 患者、22 例 BC CML 患者和 11 对慢性期和 BC CML 患者中两个 miR-15/16 簇的表达。与慢性期 CML 相比，BC CML 的 miR-15a/-15b/16 表达明显降低。此外，与慢性期 CML 相比，BC CML 中 miR-15/16 的直接靶标如 Bmi-1、ROR1 和 Bcl-2 的表达上调。这项研究强调了 miR-15/16 簇的缺失可能是 CML 患者从慢性期向 BC 转变的潜在致癌驱动因素。
