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

Moharram, Sausan A. LU ; Shah, Kinjal LU ; Khanum, Fatima; Marhäll, Alissa LU ; Mohiuddin, Gazi LU and Kazi, Julhash U. LU (2017) In Cancer Letters 405. p.73-78
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Apoptosis, CDK inhibitor, Cell cycle, T-ALL
in
Cancer Letters
volume
405
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85026777253
  • wos:000412036200009
ISSN
0304-3835
DOI
10.1016/j.canlet.2017.07.019
language
English
LU publication?
yes
id
3dce6bf6-a89d-47ab-97aa-bac2eae2ba46
date added to LUP
2017-08-22 15:52:18
date last changed
2018-02-11 04:31:11
@article{3dce6bf6-a89d-47ab-97aa-bac2eae2ba46,
  abstract     = {<p>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.</p>},
  author       = {Moharram, Sausan A. and Shah, Kinjal and Khanum, Fatima and Marhäll, Alissa and Mohiuddin, Gazi and Kazi, Julhash U.},
  issn         = {0304-3835},
  keyword      = {Apoptosis,CDK inhibitor,Cell cycle,T-ALL},
  language     = {eng},
  month        = {10},
  pages        = {73--78},
  publisher    = {Elsevier},
  series       = {Cancer Letters},
  title        = {Efficacy of the CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute lymphoblastic leukemia},
  url          = {http://dx.doi.org/10.1016/j.canlet.2017.07.019},
  volume       = {405},
  year         = {2017},
}