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Editorial
. 2023 Feb 9;141(6):562-564.
doi: 10.1182/blood.2022018508.

Acquired BAX mutations in AML

Won Jun Kim  1 , Omar Abdel-Wahab  1
Affiliations
Editorial

Acquired BAX mutations in AML

Won Jun Kim et al. Blood. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: O.A.-W. has served as a consultant for H3B Biomedicine, Foundation Medicine Inc, Merck, Prelude Therapeutics, and Janssen; is on the scientific advisory board of Envisagenics Inc, Alchemy, Harmonic Discovery Inc, and Pfizer Boulder; and has received prior research funding from H3B Biomedicine, Nurix Therapeutics, and LOXO Oncology, unrelated to the current manuscript. W.J.K. declares no competing financial interests.

Figures

None
Dependence of venetoclax response on BAX and development of venetoclax resistance through BAX mutations. (A) Venetoclax, by engaging BCL2 as an alternative ligand, releases proapoptotic BH3-only proteins from BCL2, which then activates apoptosis effector proteins such as BAX. BAX is found predominantly in the cytosol with its COOH-terminal transmembrane region (TMR) sequestered within its hydrophobic pocket. Once activated, BAX releases its TMR to be inserted into the OMM, where BAX oligomerizes to permeabilize the OMM and induce release of cytochrome c. (B) Acquired frameshift/nonsense mutations in BAX reduce its protein expression while inactivating missense mutations in BAX such as P168A compromises its effector functions by preventing BAX TMR release and insertion into the OMM. mRNA, messenger RNA.
See this image and copyright information in PMC

Comment on

  • Acquired mutations in BAX confer resistance to BH3-mimetic therapy in acute myeloid leukemia.
    Moujalled DM, Brown FC, Chua CC, Dengler MA, Pomilio G, Anstee NS, Litalien V, Thompson E, Morley T, MacRaild S, Tiong IS, Morris R, Dun K, Zordan A, Shah J, Banquet S, Halilovic E, Morris E, Herold MJ, Lessene G, Adams JM, Huang DCS, Roberts AW, Blombery P, Wei AH. Moujalled DM, et al. Blood. 2023 Feb 9;141(6):634-644. doi: 10.1182/blood.2022016090. Blood. 2023. PMID: 36219880 Free PMC article.

References

    1. Moujalled DM, Brown FC, Chua CC, et al. Acquired mutations in BAX confer resistance to BH3-mimetic therapy in acute myeloid leukemia. Blood. 2023;141(6):634–644. - PubMed
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