Abstract
BackgroundBCL2 protein inhibitor venetoclax (ABT-199) has been authorized by Food and Drug Administration for relapsed/refractory chronic lymphoid leukemia with 17p deletion. Although venetoclax/ABT-199 also caused cell death in acute myeloid leukemia (AML), whether it could be applied to clinical treatment needs further studies. Here, we revealed clinical implication of BCL2 overexpression in de novo adult AML, and may provide theoretical basis for targeted therapy using venetoclax.MethodsBCL2 expression was analyzed in adult AML patients from public datasets The Cancer Genome Atlas (TCGA) and confirmed by another independent cohort from our own data.ResultsBCL2 expression showed up-regulated in AML patients among TCGA data and confirmed by our own data. BCL2 overexpression was correlated with FAB-M0/M1, whereas BCL2 under-expression was related to FAB-M5. However, BCL2 expression has no effect on overall survival (OS) and leukemia-free survival (LFS) of AML patients (determined in BCL2low and BCL2high groups). Interestingly, in the BCL2low group, patients undergoing autologous or allogeneic hematopoietic stem cell transplantation (auto/allo-HSCT) had significantly better OS and LFS compared with patients only received chemotherapy, whereas, no significant difference was found in OS and LFS between chemotherapy and auto/allo-HSCT patients in the BCL2high group. BCL2 expression was found positively correlated with HOX family gene, and negatively correlated with tumor suppressor microRNA such as miR-195, miR-497, and miR-193b.ConclusionsBCL2 overexpression identified specific FAB subtypes of AML, but it did not affect prognosis. Patients with BCL2 overexpression did not benefit from auto/allo-HSCT among whole-cohort-AML and cytogenetically normal AML.
Highlights
BCL2 protein inhibitor venetoclax (ABT-199) has been authorized by Food and Drug Administration for relapsed/refractory chronic lymphoid leukemia with 17p deletion
BCL2 overexpression in acute myeloid leukemia (AML) A cohort of 173 de novo adult AML patients with BCL2 expression data from public The Cancer Genome Atlas (TCGA) datasets was used for differential expression analysis
By using the GEPIA, we found BCL2 expression in AML patients was significantly increased compared with GTEx normal Bone marrow (BM) samples (P < 0.001, Fig. 1a)
Summary
BCL2 protein inhibitor venetoclax (ABT-199) has been authorized by Food and Drug Administration for relapsed/refractory chronic lymphoid leukemia with 17p deletion. Venetoclax/ABT-199 caused cell death in acute myeloid leukemia (AML), whether it could be applied to clinical treatment needs further studies. We revealed clinical implication of BCL2 overexpression in de novo adult AML, and may provide theoretical basis for targeted therapy using venetoclax. In 2016, venetoclax (ABT-199) has been authorized by FDA for relapsed/refractory chronic lymphoid leukemia (CLL) with 17p deletion. ABT-199 induced cell death in AML [12], whether it can be applied to clinical treatment needs further studies. We revealed clinical implication of BCL2 overexpression in de novo adult AML, and may provide theoretical basis for targeted therapy using BCL2 inhibitor venetoclax
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