LEDGF/p75 is dispensable for hematopoiesis but essential for MLL-rearranged leukemogenesis.

Blood
Sara El AshkarJan De Rijck

Abstract

Mixed lineage leukemia (MLL) represents a genetically distinct and aggressive subset of human acute leukemia carrying chromosomal translocations of the MLL gene. These translocations result in oncogenic fusions that mediate aberrant recruitment of the transcription machinery to MLL target genes. The N-terminus of MLL and MLL-fusions form a complex with lens epithelium-derived growth factor (LEDGF/p75; encoded by the PSIP1 gene) and MENIN. This complex contributes to the association of MLL and MLL-fusion multiprotein complexes with the chromatin. Several studies have shown that both MENIN and LEDGF/p75 are required for efficient MLL-fusion-mediated transformation and for the expression of downstream MLL-regulated genes such as HOXA9 and MEIS1 In light of developing a therapeutic strategy targeting this complex, understanding the function of LEDGF/p75 in normal hematopoiesis is crucial. We generated a conditional Psip1 knockout mouse model in the hematopoietic compartment and examined the effects of LEDGF/p75 depletion in postnatal hematopoiesis and the initiation of MLL leukemogenesis. Psip1 knockout mice were viable but showed several defects in hematopoiesis, reduced colony-forming activity in vitro, decreased expression of Ho...Continue Reading

Citations

Jun 20, 2019·Cancers·Mélanie LambertMarie-Hélène David-Cordonnier
Jun 4, 2019·Frontiers in Cell and Developmental Biology·Anthony K N Chan, Chun-Wei Chen
Jun 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mélanie LambertMarie-Hélène David-Cordonnier
Jul 20, 2019·Scientific Reports·Stephen G R BarnardElizabeth Ainsbury
Dec 12, 2020·International Journal of Molecular Sciences·Elzbieta PorebaJulia Durzynska

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