Gene expression profiling suggests that Gata2, a hematopoietic transcription factor, is a top upregulated gene in preleukemic Cbfb-MYH11 knockin mice and is expressed in human inv(16) AML.
AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM accounts for 1% to 2% of all forms of AML and has been associated with a younger age at diagnosis, a poor response to standard induction chemotherapy, and very poor long-term prognosis.
Thus, GATA2 acts as a critical regulator of normal and leukemic stem cells and mediates transcriptional networks that may be exploited therapeutically to target key facets of LSC behavior in AML.
GATA2 and RUNX1 deficiency is not associated with host susceptibility to DNA damage, and therefore, conventional treatment strategies for MDS and AML can be used.
By pooling heterogeneous data from three independent AML cohorts with paired DNA and RNA sequencing (N = 253), we could validate the preferential transcription of GATA2-mutated alleles.
Thus, we define novel insights into the oncogenic role of GATA2 in human AML cells and suggest the potential utilization of transient GATA2 therapeutic targeting in AML.
In conclusion, GATA2 ZF1 mutations are associated with distinct clinico-biological features and predict better prognosis, different from ZF2 mutations, in AML patients.
Patients with GATA2 (Emberger syndrome) deficiency needs early hematopoietic stem cell transplant (HSCT) before evolving in to myelodysplastic syndrome or acute myeloid leukemia and with time given compromised organ dysfunction leads to increase regimen-related toxicities.
Individuals with germline mutations of either RUNX1, CEBPA, or GATA2 can also be called as preleukemic because they have a markedly increased incidence of evolution into AML.
As GATA2 mRNA correlated with IL1B and CXCL2 mRNAs in AML-M5 and high expression of these genes predicted poor prognosis of cytogenetically normal AML, we propose that the circuit is functionally important in specific AML contexts.
Mutation in GATA2 results in the loss of function or even gain of function, including abnormal proliferation of white blood cells that may predispose to acute myeloid leukemia.
Germline GATA2 mutations are involved in a group of complex syndromes with overlapping clinical features of immune deficiency, lymphedema and propensity to acute myeloid leukemia or myelodysplastic syndrome (AML-MDS).
Thus, we conducted whole-genome sequencing on a patient with a germline GATA-2 heterozygous mutation (c. 988 C > T; p. R330X), who had a history suggestive of immunodeficiency and evolved into MDS/AML.
We show that GATA2(low) AML lack the prototypical R882 mutation in DNMT3A frequently observed in NK-AML patients and that The Cancer Genome Atlas AML specimens with DNMT3A R882 mutations are characterized by CpG hypomethylation of GATA2.