GATA2 deficiency: enhancer deregulation, immune surveillance failure, and clonal evolution.

Samuele Roncareggi; Francesco Saettini

doi:10.1016/j.coi.2026.102817

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GATA2 deficiency: enhancer deregulation, immune surveillance failure, and clonal evolution.

Samuele Roncareggi·Francesco Saettini

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Abstract

Germline mutations in GATA2 cause a syndromic inborn error of immunity characterized by cytopenia, infections, immune dysregulation, and a marked predisposition to myelodysplastic syndrome and acute myeloid leukemia. Initially defined by the DCML phenotype-dendritic cell, monocyte, B- and NK-cell deficiency-GATA2 deficiency is now recognized as a disorder of global immune-hematopoietic homeostasis. Recent multi-omics and experimental models reveal enhancer-driven inflammatory rewiring, IRF8-dependent lineage imbalance, and premature hematopoietic aging. In parallel, adaptive immune defects, including impaired B- and T-cell development and function, contribute to defective immune surveillance. These alterations not only explain susceptibility to infection but also shape clonal evolution and malignant transformation. Clinically, improved risk stratification and transplant outcomes underscore the importance of early recognition and monitoring of immune dysfunction. GATA2 deficiency thus represents a paradigm linking immune dysregulation, inflammatory stress, and cancer predisposition.

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Humans Animals GATA2 Deficiency Immunologic Surveillance GATA2 Transcription Factor Clonal Evolution Enhancer Elements, Genetic Journal Article Review

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Samuele Roncareggi, Francesco Saettini. 2026-07-15. GATA2 deficiency: enhancer deregulation, immune surveillance failure, and clonal evolution.. https://doi.org/10.1016/j.coi.2026.102817

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