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Original Paper

Effects of Jak2 Type 1 Inhibitors NVP-BSK805 and NVP-BVB808 on Jak2 Mutation-Positive and Bcr-Abl-Positive Cell Lines

Ringel F.a · Kaeda J.a · Schwarz M.a · Oberender C.a · Grille P.a · Dörken B.a · Marque F.b · Manley P.W.c · Radimerski T.b · le Coutre P.a

Author affiliations

aMedizinische Klinik m.S. Hämatologie und Onkologie, Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, Berlin, Germany; bDisease Area Oncology, and cGlobal Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel, Switzerland

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Acta Haematol 2014;132:75-86

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: January 09, 2013
Accepted: October 15, 2013
Published online: January 31, 2014
Issue release date: June 2014

Number of Print Pages: 12
Number of Figures: 5
Number of Tables: 2

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: https://www.karger.com/AHA

Abstract

Janus kinases are critical components of signaling pathways that regulate hematopoiesis. Mutations of the non-receptor tyrosine kinase JAK2 are found in many BCR-ABL-negative myeloproliferative neoplasms. Preclinical results support that JAK2 inhibitors could show efficacy in treating chronic myeloproliferative neoplasms. JAK2 has also been postulated to play a role in BCR-ABL signal transduction. Therefore, inhibitors of JAK2 kinases are turning into therapeutic strategies for treatment of chronic myelogenous leukemia (CML). In this study, the effects of two novel JAK2 inhibitors, NVP-BSK805 and NVP-BVB808, have been investigated in cell lines expressing either BCR-ABL or mutant JAK2. Possible synergies between NVP-BSK805/NVP-BVB808 and the kinase inhibitors imatinib and nilotinib were assessed. Proliferation and apoptosis tests with both substances showed response in the following cell lines: CHRF-288-11, SET-2 and UKE-1. All BCR-ABL-positive cell lines showed some reduction in proliferation, but with half-maximal growth-inhibitory values >1 µM. Combination of the JAK2 inhibitors with imatinib and nilotinib showed no significant additive or synergistic effects, although all BCR-ABL-positive cell lines responded well to both CML therapeutic agents. Interestingly, it seemed that the combination of imatinib with NVP-BSK805 had a protective effect on the cells. Combination treatment with nilotinib did not show this effect.

© 2014 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: January 09, 2013
Accepted: October 15, 2013
Published online: January 31, 2014
Issue release date: June 2014

Number of Print Pages: 12
Number of Figures: 5
Number of Tables: 2

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: https://www.karger.com/AHA


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