TY - JOUR
T1 - Heterogeneous nuclear ribonucleoprotein K is overexpressed in acute myeloid leukemia and causes myeloproliferation in mice via altered Runx1 splicing
AU - Aitken, Marisa J.L.
AU - Malaney, Prerna
AU - Zhang, Xiaorui
AU - Herbrich, Shelley M.
AU - Chan, Lauren
AU - Benitez, Oscar
AU - Rodriguez, Ashley G.
AU - Ma, Huaxian
AU - Jacamo, Rodrigo
AU - Duan, Ruizhi
AU - Link, Todd M.
AU - Kornblau, Steven M.
AU - Kanagal-Shamanna, Rashmi
AU - Bueso-Ramos, Carlos E.
AU - Post, Sean M.
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of NAR Cancer.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Acute myeloid leukemia (AML) is driven by numerous molecular events that contribute to disease progression. Herein, we identify hnRNP K overexpression as a recurrent abnormality in AML that negatively correlates with patient survival. Overexpression of hnRNP K in murine fetal liver cells results in altered self-renewal and differentiation potential. Further, murine transplantation models reveal that hnRNP K overexpression results in myeloproliferation in vivo. Mechanistic studies expose a direct functional relationship between hnRNP K and RUNX1 - a master transcriptional regulator of hematopoiesis often dysregulated in leukemia. Molecular analyses show that overexpression of hnRNP K results in an enrichment of an alternatively spliced isoform of RUNX1 lacking exon 4. Our work establishes hnRNP K's oncogenic potential in influencing myelogenesis through its regulation of RUNX1 splicing and subsequent transcriptional activity.
AB - Acute myeloid leukemia (AML) is driven by numerous molecular events that contribute to disease progression. Herein, we identify hnRNP K overexpression as a recurrent abnormality in AML that negatively correlates with patient survival. Overexpression of hnRNP K in murine fetal liver cells results in altered self-renewal and differentiation potential. Further, murine transplantation models reveal that hnRNP K overexpression results in myeloproliferation in vivo. Mechanistic studies expose a direct functional relationship between hnRNP K and RUNX1 - a master transcriptional regulator of hematopoiesis often dysregulated in leukemia. Molecular analyses show that overexpression of hnRNP K results in an enrichment of an alternatively spliced isoform of RUNX1 lacking exon 4. Our work establishes hnRNP K's oncogenic potential in influencing myelogenesis through its regulation of RUNX1 splicing and subsequent transcriptional activity.
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U2 - 10.1093/narcan/zcac039
DO - 10.1093/narcan/zcac039
M3 - Article
C2 - 36518526
AN - SCOPUS:85145403739
SN - 2632-8674
VL - 4
JO - NAR Cancer
JF - NAR Cancer
IS - 4
M1 - zcac039
ER -