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hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies.

Abstract
hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk(+/-)). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling. Additionally, analysis of samples from primary acute myeloid leukemia patients harboring a partial deletion of chromosome 9 revealed a significant decrease in HNRNPK expression. Together, these data implicate hnRNP K in the development of hematological disorders and suggest hnRNP K acts as a tumor suppressor.
AuthorsMiguel Gallardo, Hun Ju Lee, Xiaorui Zhang, Carlos Bueso-Ramos, Laura R Pageon, Mark McArthur, Asha Multani, Aziz Nazha, Taghi Manshouri, Jan Parker-Thornburg, Inmaculada Rapado, Alfonso Quintas-Cardama, Steven M Kornblau, Joaquin Martinez-Lopez, Sean M Post
JournalCancer cell (Cancer Cell) Vol. 28 Issue 4 Pg. 486-499 (Oct 12 2015) ISSN: 1878-3686 [Electronic] United States
PMID26412324 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • HNRNPK protein, mouse
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • Ribonucleoproteins
  • HNRNPK protein, human
Topics
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Chromosomal Instability
  • Chromosomes, Human, Pair 9 (genetics)
  • Gene Expression Regulation, Neoplastic
  • Gene Knockout Techniques
  • Haploinsufficiency
  • Hematologic Neoplasms (genetics, metabolism, pathology)
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • Humans
  • Mice
  • Ribonucleoproteins (genetics, metabolism)
  • Signal Transduction
  • Survival Analysis

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