NDLI: PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases

Content Provider	PubMed Central
Author	Esperanza, Martín-sánchez Lina, Odqvist Rodríguez-pinilla, Socorro M. Margarita, Sánchez-beato Roncador, Giovanna Beatriz, Domínguez-gonzález Carmen, Blanco-aparicio Collazo, Ana M. García Cantalapiedra, Esther González Fernández, Joaquín Pastor Olmo, Soraya Curiel Del Pisonero, Helena Madureira, Rebeca Almaraz, Carmen Mollejo, Manuela Alves, F. Javier Javier, Menárguez Fernando, González-palacios Luis, Rodríguez-peralto José Ortiz-romero, Pablo L. Real, Francisco X. García, Juan F. Bischoff, James R. Piris, Miguel A.
Editor	Climent, Jose Angel Martinez
Copyright Year	2014
Abstract	Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL). The Proviral Integration site of Moloney murine leukemia virus (PIM) kinases are important mediators of cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs) and pharmacologically (mainly with the pan-PIM inhibitor (PIMi) ETP-39010) in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL) cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.
Related Links	http://dx.doi.org/10.1371/journal.pone.0112148
Starting Page	112148
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	11
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

RNA Inhibition Highlights Cyclin D1 as a Potential Therapeutic Target for Mantle Cell Lymphoma

Identification and Characterization of Peripheral T-Cell Lymphoma-Associated SEREX Antigens

Characterization of a New Mouse Model for Peripheral T Cell Lymphoma in Humans

Aurora Kinases as Targets in Drug-Resistant Neuroblastoma Cells

Concurrent Mutations in ATM and Genes Associated with Common γ Chain Signaling in Peripheral T Cell Lymphoma

Pim Kinases Promote Migration and Metastatic Growth of Prostate Cancer Xenografts

Aurora Kinases as Druggable Targets in Pediatric Leukemia: Heterogeneity in Target Modulation Activities and Cytotoxicity by Diverse Novel Therapeutic Agents

T-cell anergy and peripheral T-cell tolerance.

TARGETgene: A Tool for Identification of Potential Therapeutic Targets in Cancer

PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases

Similar Documents

RNA Inhibition Highlights Cyclin D1 as a Potential Therapeutic Target for Mantle Cell Lymphoma

Identification and Characterization of Peripheral T-Cell Lymphoma-Associated SEREX Antigens

Characterization of a New Mouse Model for Peripheral T Cell Lymphoma in Humans

Aurora Kinases as Targets in Drug-Resistant Neuroblastoma Cells

Concurrent Mutations in ATM and Genes Associated with Common γ Chain Signaling in Peripheral T Cell Lymphoma

Pim Kinases Promote Migration and Metastatic Growth of Prostate Cancer Xenografts

Aurora Kinases as Druggable Targets in Pediatric Leukemia: Heterogeneity in Target Modulation Activities and Cytotoxicity by Diverse Novel Therapeutic Agents

T-cell anergy and peripheral T-cell tolerance.

TARGETgene: A Tool for Identification of Potential Therapeutic Targets in Cancer

PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases