hnRNP K is a haploinsufficient tumor suppressor that regulates proliferation and differentiation programs in hematologic malignancies
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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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hnRNP K, SRSF3, and YB-1 show altered expression in AML and contribute to leukemia progression.
“In addition, the expression of hnRNP K (40), SRSF3 (SRp20) (41), and YB-1 (42) has been shown to be altered in AML, but also to contribute to leukemia progression.”
From Discovery of a Novel CIP2A Variant (NOCIVA) with Clinical Relevance in Predicting TKI Resistance in Myeloid Leukemias (2021) · cites this paper as [40]
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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.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 28
- Issue
- 4
- Pages
- 486-499
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4652598
- 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
- bronze
- doi.org
- Licence
- 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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