Polycomb group protein Mel18 inhibits hematopoietic stem cell self-renewal through repressing the transcription of self-renewal and proliferation genes.

Polycomb group (PcG) proteins play important roles in hematopoietic stem cell (HSC) self-renewal. Mel18 and Bmi1 are homologs of the PCGF subunit within the Polycomb repressive complex 1 (PRC1). Bmi1 (PCGF4) enhances HSC self-renewal and promotes terminal differentiation.

PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation.

Unlabelled: Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival.

PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371.

Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. FMS-like tyrosine kinase receptor-3 (FLT3) is one of the major oncogenic receptor tyrosine kinases aberrantly activated in AML. Although protein tyrosine phosphatase PRL2 is highly expressed in some subtypes of AML compared with normal human hematopoietic stem and progenitor cells, the mechanisms by which PRL2 promotes leukemogenesis are largely unknown.

Role of p53 in regulation of hematopoiesis in health and disease.

Purpose Of Review: Human aging is associated with an exponential increase in the occurrence of clonal hematopoiesis of indeterminate potential (CHIP). CHIP is associated with increased risks of de novo and therapy-related hematologic neoplasms and serves as a reservoir for leukemic relapse. Somatic mutations in the TP53 gene, which encodes the tumor suppressor protein p53, rank in the top five among genes that were mutated in CHIP.

Author Correction: Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.