Cited by 146Acute Myeloid Leukemia ResearchCancer-related Molecular PathwaysRNA Research and Splicing

hnRNP K is a haploinsufficient tumor suppressor that regulates proliferation and differentiation programs in hematologic malignancies

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Gallardo, Miguel, Lee, Hun Ju, Zhang, Xiaorui, Bueso-Ramos, Carlos, Pageon, Laura R., McArthur, Mark, Multani, Asha, Nazha, Aziz +7 more·2015·Cancer Cell

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.

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Authors
Gallardo, M., Lee, H. J., Zhang, X., Bueso-Ramos, C., Pageon, L. R., McArthur, M., Multani, A., Nazha, A., Manshouri, T., Parker-Thornburg, J., Rapado, I., Quintas-Cardama, A., Kornblau, S. M., Martinez-Lopez, J., & Post, S. M.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Hospital Universitario 12 De Octubre (ES)
Corresponding author
Post, Sean M.
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2015-10
Volume
28
Issue
4
Pages
486-499
ISSN
1535-6108 (ISSN-L)
OpenAlex
W2168139795
Cited by
145
References
36
Citations by year
2026: 11 · 2025: 12 · 2024: 4 · 2023: 15 · 2022: 15 · 2021: 21 · 2020: 13 · 2019: 22 · 2018: 14 · 2017: 12 · 2016: 5 · 2015: 1
FWCI
8.39
Type
journal article
Language
en
Open access
Locations
  • Cancer Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Texas MD Anderson Cancer Center
  • National Cancer Institute (P50CA100632, CA-16672, P50 CA1000632-09, P30CA016672)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
hnRNP K, haploinsufficiency, tumor suppressor, hematologic malignancies, acute myeloid leukemia, chromosome 9 deletion, myeloproliferation, STAT3 signaling, p21, C/EBP, genomic instability, cell proliferation, cell differentiation
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Chromosomes, Human, Pair 9, Humans, Ribonucleoproteins, Signal Transduction, Gene Expression Regulation, Neoplastic, Survival Analysis, Hematologic Neoplasms, Heterogeneous-Nuclear Ribonucleoprotein K, Chromosomal Instability, Cell Proliferation, Mice, Gene Knockout Techniques, Haploinsufficiency

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