Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells

Alejo A. Morales, Metin Kurtoglu, Shannon M. Matulis, Jiangxia Liu, David Siefker, Delia M. Gutman, Jonathan L. Kaufman, Kelvin P. Lee, Sagar Lonial, Lawrence H. Boise

Research output: Contribution to journalArticle

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Abstract

Dependence on Bcl-2 proteins is a common feature of cancer cells and provides a therapeutic opportunity. ABT-737 is an antagonist of antiapoptotic Bcl-2 proteins and therefore is a good predictor of Bcl-xL/Bcl-2 dependence. Surprisingly, analysis of Mcl-1-dependent multiple myeloma cell lines revealed codependence on Bcl-2/Bcl-xL in half the cells tested. Codependence is not predicted by the expression level of antiapoptotic proteins, rather through interactions with Bim. Consistent with these findings, acquired resistance to ABT-737 results in loss of codependence through redistribution of Bim to Mcl-1. Overall, these results suggest that complex interactions, and not simply expression patterns of Bcl-2 proteins, need to be investigated to understand Bcl-2 dependence and how to better use agents, such as ABT-737.

Original languageEnglish (US)
Pages (from-to)1329-1339
Number of pages11
JournalBlood
Volume118
Issue number5
DOIs
StatePublished - Aug 4 2011

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Proteins
Cells
Multiple Myeloma
Cell Line
Codependency (Psychology)
ABT-737
Neoplasms
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Morales, A. A., Kurtoglu, M., Matulis, S. M., Liu, J., Siefker, D., Gutman, D. M., ... Boise, L. H. (2011). Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells. Blood, 118(5), 1329-1339. https://doi.org/10.1182/blood-2011-01-327197

Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells. / Morales, Alejo A.; Kurtoglu, Metin; Matulis, Shannon M.; Liu, Jiangxia; Siefker, David; Gutman, Delia M.; Kaufman, Jonathan L.; Lee, Kelvin P.; Lonial, Sagar; Boise, Lawrence H.

In: Blood, Vol. 118, No. 5, 04.08.2011, p. 1329-1339.

Research output: Contribution to journalArticle

Morales, AA, Kurtoglu, M, Matulis, SM, Liu, J, Siefker, D, Gutman, DM, Kaufman, JL, Lee, KP, Lonial, S & Boise, LH 2011, 'Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells', Blood, vol. 118, no. 5, pp. 1329-1339. https://doi.org/10.1182/blood-2011-01-327197
Morales, Alejo A. ; Kurtoglu, Metin ; Matulis, Shannon M. ; Liu, Jiangxia ; Siefker, David ; Gutman, Delia M. ; Kaufman, Jonathan L. ; Lee, Kelvin P. ; Lonial, Sagar ; Boise, Lawrence H. / Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells. In: Blood. 2011 ; Vol. 118, No. 5. pp. 1329-1339.
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AU - Liu, Jiangxia

AU - Siefker, David

AU - Gutman, Delia M.

AU - Kaufman, Jonathan L.

AU - Lee, Kelvin P.

AU - Lonial, Sagar

AU - Boise, Lawrence H.

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