The role of the GATA2 transcription factor in normal and malignant hematopoiesis

Vicente, Carmen; Conchillo, Ana; Garcı́a-Sánchez, Asunción; Odero, Marı́a D.

doi:10.1016/j.critrevonc.2011.04.007

Cited by 143 publications

(129 citation statements)

References 176 publications

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“…Bigley et al transplanted 2 patients with an autosomal dominant monocytopenia syndrome that is most probably GATA2 deficiency. 2 GATA2 is crucial for the manteinance of HSCs, 17 but it also plays a critical role in the transcriptional regulation of endothelial nitric oxide synthetase (eNOS). 18,19 Some of the pulmonary changes seen in GATA2 deficiency likely result from pulmonary alveolar macrophage dysfunction and defective eNOS expression in the pulmonary epithelium.…”

Section: Discussionmentioning

confidence: 99%

Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency

Cuéllar-Rodríguez

Gea-Banacloche

Freeman

et al. 2011

Blood

130

104

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Section: Discussionmentioning

confidence: 99%

Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency

Cuéllar-Rodríguez

Gea-Banacloche

Freeman

et al. 2011

Blood

130

104

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“…The zinc-finger domains of GATA2 that mediate DNA binding and interaction with transcriptional partners (Vicente et al, 2012) are largely conserved between zebrafish Gata2a and Gata2b and the human and mouse GATA2 proteins. Outside this region the proteins are more divergent, and it is not clear which regions are responsible for the different functions performed by Gata2a and Gata2b.…”

Section: Subfunctionalization Of Gata2a and Gata2b In Zebrafishmentioning

confidence: 99%

Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo

et al. 2015

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The adult blood system is established by hematopoietic stem cells (HSCs), which arise during development from an endothelial-tohematopoietic transition of cells comprising the floor of the dorsal aorta. Expression of aortic runx1 has served as an early marker of HSC commitment in the zebrafish embryo, but recent studies have suggested that HSC specification begins during the convergence of posterior lateral plate mesoderm (PLM), well before aorta formation and runx1 transcription. Further understanding of the earliest stages of HSC specification necessitates an earlier marker of hemogenic endothelium. Studies in mice have suggested that GATA2 might function at early stages within hemogenic endothelium. Two orthologs of Gata2 exist in zebrafish: gata2a and gata2b. Here, we report that gata2b expression initiates during the convergence of PLM, becoming restricted to emerging HSCs. We observe Notch-dependent gata2b expression within the hemogenic subcompartment of the dorsal aorta that is in turn required to initiate runx1 expression. Our results indicate that Gata2b functions within hemogenic endothelium from an early stage, whereas Gata2a functions more broadly throughout the vascular system.

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“…GATA1 is encoded on the X chromosome and is typically present in erythroid, megakaryocytic, mast, and eosinophilic lineage cells [28][29][30][31]. GATA2, encoded on chromosome 3, is crucial for the proliferation and survival of early hematopoietic cells, and as a partner of GATA1 is also involved in lineage-specific transcriptional regulation [32]. GATA3, encoded on chromosome 10, plays an essential role in T cell development and immune regulation [33].…”

Section: Gata1 Mutation Induces Tam In Ds Neonatesmentioning

confidence: 99%

Evolution of myeloid leukemia in children with Down syndrome

Saida

2016

Int J Hematol

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the general population, the distribution of malignancies is different [3]. Patients with DS show a unique spectrum of malignancies, with a 10-to 20-fold higher risk of acute leukemia and a lower incidence of solid tumors [3,4]. Death from malignancies other than leukemia is strikingly less common in patients of all ages in DS, and death from leukemia is more likely in children younger than 10 years of age with DS than in those without [5]. The most frequent form of leukemia during childhood, both with and without DS, is acute lymphoblastic leukemia (ALL), and the incidence of ALL in children with DS is approximately 20-fold higher than in non-DS children [3]. However, the most marked increase in incidence in DS infants is with acute megakaryoblastic leukemia (AMKL), a myeloid malignancy of platelet precursors. The relative risk of developing AMKL is estimated to be 500 times higher in children with DS than in the general population [6]. Unlike AMKL in non-DS patients, most AMKL associated with DS (DS-AMKL) patients usually respond well to chemotherapy.In most cases, DS-AMKL is preceded by a temporary form of megakaryoblastic leukemia unique to newborns with DS and known as transient abnormal myelopoiesis (TAM) or transient leukemia. TAM, a clonal myeloproliferative syndrome, presents in the fetus or a few days after birth and in most cases resolves spontaneously within 3 months [7,8]. Typically, TAM is characterized by the presence of high numbers of circulating blast cells expressing CD33, CD38, CD117, CD34, CD7, CD56, CD36, CD71, and CD42b [9], which are indistinguishable from blasts observed in DS-AMKL. More often, the clinical presentation of TAM varies from asymptomatic alterations in the blood count to disseminated leukemic infiltration. Clinically severe TAM (liver failure, pleural/pericardial effusion, ascites, renal failure, and coagulopathy) affects 10-30 % of patients with clinically diagnosed TAM, and Abstract Children with Down syndrome (DS) have a markedly increased risk of leukemia. They are at particular risk of acute megakaryoblastic leukemia, known as myeloid leukemia associated with DS (ML-DS), the development of which is closely linked to a preceding temporary form of neonatal leukemia called transient abnormal myelopoiesis (TAM). Findings from recent clinical and laboratory studies suggest that constitutional trisomy 21 and GATA1 mutation(s) cause TAM, and that additional genetic alteration(s) including those in epigenetic regulators and signaling molecules are involved in the progression from TAM to ML-DS. Thus, this disease progression represents an important model of multi-step leukemogenesis. The present review focuses on the evolutionary process of TAM to ML-DS, and advances in the understanding of perturbed hematopoiesis in DS with respect to GATA1 mutation and recent findings, including cooperating genetic events, are discussed.

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The role of the GATA2 transcription factor in normal and malignant hematopoiesis

Cited by 143 publications

References 176 publications

Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency

Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency

Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo

Evolution of myeloid leukemia in children with Down syndrome

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