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

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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, Manshouri, Taghi, Parker-Thornburg, Jan, Rapado, Inmaculada, Quintas-Cardama, Alfonso, Kornblau, Steven M., Martinez-Lopez, Joaquin, Post, Sean M.·2015·Cancer Cell

DOI 10.1016/j.ccell.2015.09.001PMC PMC4652598

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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.
ORCID: Gallardo, Miguel
Lee, Hun Ju
Zhang, Xiaorui
Bueso-Ramos, Carlos
Pageon, Laura R.
Multani, Asha
Nazha, Aziz
Manshouri, Taghi
Kornblau, Steven M.
Post, Sean M.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2015-10
Volume: 28
Issue: 4
Pages: 486-499
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccell.2015.09.001
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
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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hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies

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