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Journal of Hematology and Oncology

, 7:95

First Online: 10 December 2014Received: 22 September 2014Accepted: 04 December 2014DOI: 10.1186-s13045-014-0095-z

Cite this article as: Mondello, P., Cuzzocrea, S. & Mian, M. J Hematol Oncol 2014 7: 95. doi:10.1186-s13045-014-0095-z

Abstract

The proviral insertion in murine PIM lymphoma proteins are a serine-threonine kinase family composed of three isoformes: Pim-1, Pim-2 and Pim-3. They play a critical role in the control of cell proliferation, survival, homing and migration. Recently, overexpression of Pim kinases has been reported in human tumors, mainly in hematologic malignancies. In vitro and in vivo studies have confirmed their oncogenic potential. Indeed, PIM kinases have shown to be involved in tumorgenesis, to enhance tumor growth and to induce chemo-resistance, which is why they have become an attractive therapeutic target for cancer therapy. Novel molecules inhibiting Pim kinases have been evaluated in preclinical studies, demonstrating to be effective and with a favorable toxicity profile. Given the promising results, some of these compounds are currently under investigation in clinical trials. Herein, we provide an overview of the biological activity of PIM-kinases, their role in hematologic malignancies and future therapeutic opportunities.

KeywordsPim kinases Target therapy Hematologic malignancies Pim inhibitors AbbreviationsPIMProviral insertion in murine

ILInterleukin

GM-CSFGranulocyte-macrophage colony-stimulating factor

G-CSFGranulocyte-colony stimulating factor

ABLAbleson

JAK2Janus Kinase 2

FLT3FMS-like tyrosine kinase 3

MuLVMurine leukemia virus

MCVMean cell volume

HSCsHematopoietic stem cells

BadBcl-2–associated agonist of cell death

SerSerine

ASK1Apoptosis signaling kinase 1

ThrThreonine

C-TAKCdc25C-associated kinase

SOCSSuppressor of Cytokine Signalling

H3S10Histone H3 phosphorylate at Ser10

BRD4Bromodomain-containing protein 4

P-TEFbPositive transcription elongation factor b

Pol IIPolymerase II

PI3K-Akt-mTORPhosphoinositide-3 Kinase-Akt-mammalian

eIF4BEukaryotic initiation factor 4B

CXCL12-CXCR4Chemokine ligand 12-chemokine C-X-C motif receptor 4

ERK1-2Extracellular signal-regulated protein kinase 1-2

MLLMixed-line-age leukemia

ABCActivated B-cell

MCLMantle cell lymphoma

FLFollicular lymphoma

MZL-MALTMarginal zone lymphoma-MALT type

CLLChronic lymphocytic leukemia

NMZLNodal marginal zone lymphoma

IC5050% inhibitory concentration

Electronic supplementary materialThe online version of this article doi:10.1186-s13045-014-0095-z contains supplementary material, which is available to authorized users.

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Autor: Patrizia Mondello - Salvatore Cuzzocrea - Michael Mian

Fuente: https://link.springer.com/







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