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BH 3 mimetic ABT ‐737 induces apoptosis in CD 34 + acute myeloid leukemia cells and shows synergistic effect with conventional chemotherapeutic drugs
Author(s) -
Rao Jia,
Li Fei,
Zhang Rongyan,
Zhou Huanhuan,
Chen Guoan
Publication year - 2017
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.12420
Subject(s) - daunorubicin , myeloid leukemia , cytarabine , apoptosis , cytotoxic t cell , cancer research , haematopoiesis , annexin , cd34 , cell culture , microbiology and biotechnology , leukemia , bone marrow , myeloid , chemistry , biology , immunology , stem cell , biochemistry , in vitro , genetics
Aims Acute myeloid leukemia ( AML ) is an immunophenotypically heterogenous malignant disease. The early immature CD 34 + AML cell subpopulation is frequently impervious to intensive chemotherapy, making them largely responsible for relapse of AML . CD 34 + AML cells have higher level of B cl‐2 protein expression than the CD 34 − subpopulation. As such, development of drugs that specifically target the B cl‐2 may have the potential to eliminate immature CD 34 + AML progenitor cells and provide therapeutic benefit. In this work, we made an attempt to investigate the cytotoxic effect of a novel B cl‐2 family inhibitor, ABT ‐737, on CD 34 + AML cell lines ( KG 1a and K asumi‐1) as well as CD 34 + primary AML cells. Methods Primary human CD 34 + cells were isolated from bone marrow mononuclear cells using CD 34 M icro B ead kit. The growth inhibitory effect was measured by cell counting kit‐8. Apoptosis was analyzed by annexin V / PI assays. Protein expression was determined by W estern blotting analysis. Results Inhibition of B cl‐2 by ABT ‐737 effectively inhibited growth and induced apoptosis in CD 34 + AML cell lines and CD 34 + primary AML cells without affecting CD 34 + normal hematopoietic cells. Furthermore, Western blot analysis showed that ABT ‐737 induced apoptosis associated with caspase‐3 activation and poly ADP‐ribose polymerase (PARP) degradation. Finally, ABT ‐737 synergistically enhanced the cytotoxic effect of cytarabine and daunorubicin in CD 34 + AML cells. Conclusion Taken together, these findings indicate that ABT ‐737 may offer as a promising molecular targeting agent in CD 34 + AML .