Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Oct 6;128(14):1834-1844.
doi: 10.1182/blood-2016-03-704908. Epub 2016 Jul 27.

Hierarchy for targeting prosurvival BCL2 family proteins in multiple myeloma: pivotal role of MCL1

Jia-Nan Gong  1   2 , Tiffany Khong  3 , David Segal  1   2 , Yuan Yao  1   2   4 , Chris D Riffkin  1 , Jean-Marc Garnier  1   2 , Seong Lin Khaw  1   2   5 , Guillaume Lessene  1   2   6 , Andrew Spencer  3 , Marco J Herold  1   2 , Andrew W Roberts  1   2   7   8 , David C S Huang  1   2
Affiliations
Free article

Hierarchy for targeting prosurvival BCL2 family proteins in multiple myeloma: pivotal role of MCL1

Jia-Nan Gong et al. Blood. .
Free article

Abstract

New therapeutic targets are needed to address the poor prognosis of patients with high-risk multiple myeloma. Myeloma cells usually express a range of the prosurvival BCL2 proteins. To define the hierarchy of their relative importance for maintaining the survival of myeloma cells, we targeted each of them in a large panel of cell lines, using pharmacological inhibitors or gene editing or by peptide-based approaches, alone or in combination. The majority of well-established immortalized cell lines (17/25) or low-passage myeloma cell lines (5/7) are readily killed when MCL1 is targeted, even including those cell lines sensitive to BCL2 inhibition. Targeting MCL1 also constrained the growth of myeloma in vivo. We also identified a previously unrecognized subset of myeloma that is highly BCLXL-dependent, and has the potential for cotargeting MCL1 and BCLXL. As MCL1 is pivotal for maintaining survival of most myelomas, it should be prioritized for targeting in the clinic once high-quality, validated inhibitors become available.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms