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.
(Less)
- author
- Moharram, Sausan A.
LU
; Shah, Kinjal
LU
; Khanum, Fatima
; Marhäll, Alissa
LU
; Mohiuddin, Gazi
LU
and Kazi, Julhash U.
LU
- organization
- publishing date
- 2017-10-01
- 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
-
- pmid:28756008
- wos:000412036200009
- scopus:85026777253
- 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
- 2024-08-05 02:54:45
@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}},
keywords = {{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}},
doi = {{10.1016/j.canlet.2017.07.019}},
volume = {{405}},
year = {{2017}},
}