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Cancer Lett. 2017 Oct 1;405:73-78. doi: 10.1016/j.canlet.2017.07.019. Epub 2017 Jul 26.

Efficacy of the CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute lymphoblastic leukemia.

Author information

1
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden.
2
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden. Electronic address: kazi.uddin@med.lu.se.

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease of the blood affecting children, adolescents and adults. Although current treatment protocols for T-ALL have improved overall survival, a portion of T-ALL patients still experiences treatment failure. Thus, the development of novel therapies is needed. In this study, we used several patient-derived T-ALL cell lines to screen for an effective drug for T-ALL. Using a panel of 378 inhibitors against different kinases, we identified the CDK inhibitor dinaciclib as a potential drug for T-ALL. Dinaciclib treatment significantly reduced cell viability and completely blocked colony formation. Furthermore, cells treated with dinaciclib showed decreased expression of several pro-survival proteins including survivin, cyclin T1 and c-MYC. Dinaciclib treatment also increased accumulation of cells in G2/M phase and significantly induced apoptosis. Finally, dinaciclib extended survival of mice in a T-ALL cell xenograft model. Collectively, these data suggest that the CDK inhibitor dinaciclib is an active drug for T-ALL in the preclinical settings.

KEYWORDS:

Apoptosis; CDK inhibitor; Cell cycle; T-ALL

PMID:
28756008
DOI:
10.1016/j.canlet.2017.07.019
[Indexed for MEDLINE]

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