Combination of Pim kinase inhibitors and Bcl-2 antagonists in chronic lymphocytic leukemia cells

被引：10

作者：

Cervantes-Gomez, Fabiola ^{[1
]}

Lavergne, Bethany ^{[1
]}

Keating, Michael J. ^{[2
]}

Wierda, William G. ^{[2
]}

Gandhi, Varsha ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77230 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77230 USA

来源：

LEUKEMIA & LYMPHOMA | 2016年 / 57卷 / 02期

关键词：

Pim kinase; CLL; ABT-199; SMI-4a; AZD1208; SGI-1776; ACUTE MYELOID-LEUKEMIA; PROSTATE-CANCER CELLS; PHOSPHORYLATES BAD; FAMILY PROTEINS; PHASE-I; EXPRESSION; APOPTOSIS; LYMPHOMA; TARGETS; GROWTH;

D O I：

10.3109/10428194.2015.1063141

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The Pim proteins are Ser/Thr kinases over-expressed in several hematological malignancies such as chronic lymphocytic leukemia (CLL) and some solid cancers like prostate cancer. Several small molecules have been developed to inhibit these kinases. In prostate cancer cell lines, the Pim kinase inhibitor SMI-4a and the Bcl-2 antagonist ABT-737 resulted in synergistic cytotoxicity. Akin to prostate cancer cells, CLL lymphocytes over-express Pim and Bcl-2 proteins. It was hypothesized that similar cytotoxic interaction should be observed in CLL. This study evaluated the in vitro cytotoxic effect of three Pim kinase inhibitors (AZD1208, SGI-1776 and SMI-4a) combined with Bcl-2 antagonists (ABT-737 or ABT-199) in malignant CLL lymphocytes. Data indicated Pim kinase inhibitors in combination with ABT-737 or ABT-199 resulted mostly in additive cytotoxicity with a few synergistic responses; however, the extent of synergism was less robust than that observed previously in prostate cancer cell lines treated with SMI-4a and ABT-737.

引用

页码：436 / 444

页数：9

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