title: 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.
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Gallardo
authors.affiliation: Department of Lymphoma & Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hun Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Histopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.affiliation: Department of Veterinary Medicine & Surgery, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Pageon
authors.affiliation: Department of Veterinary Medicine & Surgery, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: McArthur
authors.affiliation: Department of Genetics, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Asha
authors.initials: A
authors.lastname: Multani
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Aziz
authors.initials: A
authors.lastname: Nazha
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.affiliation: Department of Genetics, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Parker-Thornburg
authors.affiliation: Department of Hematology, Hospital Universitario 12 de Octubre and CNIO, Madrid 28041, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Rapado
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintas-Cardama
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kornblau
authors.affiliation: Department of Hematology, Hospital Universitario 12 de Octubre and CNIO, Madrid 28041, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martinez-Lopez
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: spost@mdanderson.org.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Post
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D043171:Chromosomal Instability; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D057895:Haploinsufficiency; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D051379:Mice; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: C577277:HNRNPK protein, mouse; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D012261:Ribonucleoproteins; C072074:HNRNPK protein, human