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Merestinib blocks Mnk kinase activity in acute myeloid leukemia progenitors and exhibits antileukemic effects in vitro and in vivo. Blood 2016 07 21;128(3):410-4

Date

06/17/2016

Pubmed ID

27307295

Pubmed Central ID

PMC4957163

DOI

10.1182/blood-2016-02-698704

Scopus ID

2-s2.0-85020242145   30 Citations

Abstract

Mitogen-activated protein kinase interacting protein kinases (Mnks) play important roles in the development and progression of acute myeloid leukemia (AML) by regulating eukaryotic translation initiation factor 4E (eIF4E) activation. Inhibiting Mnk1/2-induced phosphorylation of eIF4E may represent a unique approach for the treatment of AML. We provide evidence for antileukemic effects of merestinib, an orally bioavailable multikinase inhibitor with suppressive effects on Mnk activity. Our studies show that merestinib effectively blocks eIF4E phosphorylation in AML cells and suppresses primitive leukemic progenitors from AML patients in vitro and in an AML xenograft model in vivo. Our findings provide evidence for potent preclinical antileukemic properties of merestinib and support its clinical development for the treatment of patients with AML.

Author List

Kosciuczuk EM, Saleiro D, Kroczynska B, Beauchamp EM, Eckerdt F, Blyth GT, Abedin SM, Giles FJ, Altman JK, Platanias LC

Author

Sameem Abedin MD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphatases
Animals
Cation Transport Proteins
Cell Line, Tumor
Enzyme Inhibitors
Eukaryotic Initiation Factor-4E
Humans
Leukemia, Myeloid, Acute
Mice
Neoplasm Proteins
Xenograft Model Antitumor Assays