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Acute myeloid leukemia cells harboring MLL fusion genes or with the acute promyelocytic leukemia phenotype are sensitive to the Bcl-2-selective inhibitor ABT-199

Leukemia volume 28, pages 1557–1560 (2014)Cite this article

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Acute myeloid leukemia (AML) is a malignant disease of cells arising from the myeloid lineage. As a heterogeneous disease, AML consists of many different subtypes, each with different treatment sensitivities and prognoses. Despite advances in care, AML remains a difficult-to-treat disease, with overall survival being ∼25% and 65%, in the adult and pediatric populations, respectively.1, 2 A major factor contributing to treatment failure in AML is the resistance to standard chemotherapy, consisting primarily of a combination of cytarabine and an anthracycline.

Overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-xL and Mcl-1, etc.) has been shown to cause resistance to chemotherapy in many cancer types, including AML.3, 4, 5 Although inhibitors of this family have been promising, inhibition of Bcl-xL has been associated with platelet death and subsequent thrombocytopenia.5, 6 Fortunately, the recently developed ABT-199 is specific for Bcl-2, making it an attractive potential option for the treatment of AML.7, 8, 9

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Acknowledgements

This study was supported by a start-up fund from Jilin University, Changchun, China, and grants from the National Natural Science Foundation of China (NSFC 31271477 and 81200363). JTC is a predoctoral trainee supported by T32 CA009531 from the National Cancer Institute.

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Author notes

  1. X Niu and G Wang: These authors contributed equally to this work.

Authors and Affiliations

  1. National Engineering Laboratory for AIDS Vaccine, Key Laboratory for Molecular Enzymology & Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, China

    X Niu, G Wang, C Xie & Y Ge

  2. Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA

    G Wang & J W Taub

  3. Department of Pediatric Hematology and Oncology, The First Hospital of Jilin University, Changchun, China

    Y Wang & C Li

  4. Wayne State University School of Medicine, Detroit, MI, USA

    J T Caldwell

  5. Cancer Biology Graduate Program, Wayne State School of Medicine, Detroit, MI, USA

    J T Caldwell

  6. Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA

    H Edwards, C Xie & Y Ge

  7. Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA

    H Edwards, C Xie, J W Taub & Y Ge

  8. Division of Pediatric Hematology/Oncology, Children’s Hospital of Michigan, Detroit, MI, USA

    J W Taub

  9. Department of Hematology and Oncology, The First Hospital of Jilin University, Changchun, China

    H Lin

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Correspondence to Y Ge.

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Niu, X., Wang, G., Wang, Y. et al. Acute myeloid leukemia cells harboring MLL fusion genes or with the acute promyelocytic leukemia phenotype are sensitive to the Bcl-2-selective inhibitor ABT-199. Leukemia 28, 1557–1560 (2014). https://doi.org/10.1038/leu.2014.72

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