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Annual Review of Pathology: Mechanisms of Disease

Volume 19, 2024

Haploinsufficient Transcription Factors in Myeloid Neoplasms

Abstract

Many 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: () monoallelic and biallelic losses can have distinct cellular outcomes; () the activity of a TF exists in a greater range than the traditional Mendelian genetic doses; and () 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.

Keyword(s): acute myeloid leukemia, aneuploidy, haploinsufficiency, hematopoietic stem cell, myelodysplastic syndrome, transcription factor
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/content/journals/10.1146/annurev-pathmechdis-051222-013421
2024-01-24
2024-04-29
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Haploinsufficient Transcription Factors in Myeloid Neoplasms
Annual Review of Pathology: Mechanisms of Disease 19, 571 (2024); https://doi.org/10.1146/annurev-pathmechdis-051222-013421
/content/journals/10.1146/annurev-pathmechdis-051222-013421
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