Haploinsufficient Transcription Factors in Myeloid Neoplasms

Annu Rev Pathol. 2024 Jan 24;19:571-598. doi: 10.1146/annurev-pathmechdis-051222-013421. Epub 2023 Oct 31.ABSTRACTMany transcription factors (TFs) function as tumor suppressor genes with heterozygous phenotypes, yet haploinsufficiency generally has an underappreciated role in neoplasia. This is no less true in myeloid cells, which are normally regulated by a delicately balanced and interconnected transcriptional network. Detailed understanding of TF dose in this circuitry sheds light on the leukemic transcriptome. In this review, we discuss the emerging features of haploinsufficient transcription factors (HITFs). We posit that: (a) monoallelic and biallelic losses can have distinct cellular outcomes; (b) the activity of a TF exists in a greater range than the traditional Mendelian genetic doses; and (c) how a TF is deleted or mutated impacts the cellular phenotype. The net effect of a HITF is a myeloid differentiation block and increased intercellular heterogeneity in the course of myeloid neoplasia.PMID:37906947 | DOI:10.1146/annurev-pathmechdis-051222-013421

Source: Annual Review of Pathology - October 31, 2023 Category: Pathology Authors: Tanner C Martinez Megan E McNerney Source Type: research