Format

Send to

Choose Destination
Cancer Cell. 2015 Oct 12;28(4):486-499. doi: 10.1016/j.ccell.2015.09.001. Epub 2015 Sep 24.

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

Author information

1
Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
2
Department of Lymphoma & Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
3
Department of Histopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
4
Department of Veterinary Medicine & Surgery, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
5
Department of Genetics, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
6
Department of Hematology, Hospital Universitario 12 de Octubre and CNIO, Madrid 28041, Spain.
7
Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: spost@mdanderson.org.

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.

PMID:
26412324
PMCID:
PMC4652598
DOI:
10.1016/j.ccell.2015.09.001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center