GATA1 gene variants associated with thrombocytopenia and anemia

Freson, Kathleen; Wijgaerts, Anouck; Geet, Chris Van

doi:10.1080/09537104.2017.1361525

Cited by 18 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that GATA1 is located on the X chromosome, cells with GATA1 mutations exclusively express GATA1s and no full‐length GATA1 protein . Individuals without trisomy 21 who have constitutional GATA1 mutations that produce only GATA1s develop thrombocytopenia, but not TAM or ML‐DS . Thus, GATA1 mutation alone is not sufficient to transform cells into pre‐leukemic or leukemic clones.…”

Section: Pathogenesis Of Tammentioning

confidence: 99%

See 1 more Smart Citation

Recent advances in the understanding of transient abnormal myelopoiesis in Down syndrome

Watanabe

2019

Pediatrics International

View full text Add to dashboard Cite

Neonates with Down syndrome (DS) have a propensity to develop the unique myeloproliferative disorder, transient abnormal myelopoiesis (TAM). TAM usually resolves spontaneously in ≤3 months, but approximately 10% of patients with TAM die from hepatic or multi‐organ failure. After remission, 20% of patients with TAM develop acute myeloid leukemia associated with Down syndrome (ML‐DS). Blasts in both TAM and ML‐DS have trisomy 21 and GATA binding protein 1 (GATA1) mutations. Recent studies have shown that infants with DS and no clinical signs of TAM or increases in peripheral blood blasts can have minor clones carrying GATA1 mutations, referred to as silent TAM. Low‐dose cytarabine can improve the outcomes of patients with TAM and high white blood cell count. A number of studies using fetal liver cells, mouse models, or induced pluripotent stem cells have elucidated the roles of trisomy 21 and GATA1 mutations in the development of TAM. Next‐generation sequencing of TAM and ML‐DS patient samples identified additional mutations in genes involved in epigenetic regulation. Xenograft models of TAM demonstrate the genetic heterogeneity of TAM blasts and mimic the process of clonal selection and expansion of TAM clones that leads to ML‐DS. DNA methylation analysis suggests that epigenetic dysregulation may be involved in the progression from TAM to ML‐DS. Unraveling the mechanisms underlying leukemogenesis and identification of factors that predict progression to leukemia could assist in development of strategies to prevent progression to ML‐DS. Investigation of TAM, a unique pre‐leukemic condition, will continue to strongly influence basic and clinical research into the development of hematological malignancies.

show abstract

Section: Pathogenesis Of Tammentioning

confidence: 99%

“…7 Individuals without trisomy 21 who have constitutional GATA1 mutations that produce only GATA1s develop thrombocytopenia, but not TAM or ML-DS. 63,64 Thus, GATA1 mutation alone is not sufficient to transform cells into pre-leukemic or leukemic clones.…”

Section: Abnormal Hematopoiesis Associated With Trisomy 21mentioning

confidence: 99%

Recent advances in the understanding of transient abnormal myelopoiesis in Down syndrome

Watanabe

2019

Pediatrics International

View full text Add to dashboard Cite

show abstract

“…During megakaryopoiesis, transcription factors are activated in a stepwise manner, and thus, different mutations induce different disease characteristics. For instance, GATA1 mutations could affect both megakaryopoiesis and erythropoiesis [71], whereas variants of RUNX1 and ETV6 are involved in leukemia predisposition [72,73]. Other genes such as HOXA11 and MECOM are associated with bone marrow failure [74,75].…”

Section: Transcription Factors In Megakaryopoiesismentioning

confidence: 99%

Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications

Noh

2021

IJMS

View full text Add to dashboard Cite

Platelets play a critical role in hemostasis and thrombus formation. Platelets are small, anucleate, and short-lived blood cells that are produced by the large, polyploid, and hematopoietic stem cell (HSC)-derived megakaryocytes in bone marrow. Approximately 3000 platelets are released from one megakaryocyte, and thus, it is important to understand the physiologically relevant mechanism of development of mature megakaryocytes. Many genes, including several key transcription factors, have been shown to be crucial for platelet biogenesis. Mutations in these genes can perturb megakaryopoiesis or thrombopoiesis, resulting in thrombocytopenia. Metabolic changes owing to inflammation, ageing, or diseases such as cancer, in which platelets play crucial roles in disease development, can also affect platelet biogenesis. In this review, I describe the characteristics of platelets and megakaryocytes in terms of their differentiation processes. The role of several critical transcription factors have been discussed to better understand the changes in platelet biogenesis that occur during disease or ageing.

show abstract

“…71 Incomplete α-granule reduction can be found in two other genetic macro-thrombocytopenias: GATA1-RT and GFI1B-RT. 37,45,72 A mild-to-moderate granule disturbance is also present in two forms of autosomal dominant IPD with normal platelet dimension that predispose to acquired hematological malignancies: ETV6-RT (dense granules) and ANKRD26-RT (αgranules). [73][74][75] This finding can guide the direction of further testing.…”

Section: Evaluation Of the Content And Secretion Of Platelet Granulesmentioning

confidence: 99%

Diagnosing Inherited Platelet Disorders: Modalities and Consequences

2021

View full text Add to dashboard Cite

Inherited platelet disorders (IPDs) are a group of rare conditions featured by reduced circulating platelets and/or impaired platelet function causing variable bleeding tendency. Additional hematological or non hematological features, which can be congenital or acquired, distinctively mark the clinical picture of a subgroup of patients. Recognizing an IPD is challenging, and diagnostic delay or mistakes are frequent. Despite the increasing availability of next-generation sequencing, a careful phenotyping of suspected patients—concerning the general clinical features, platelet morphology, and function—is still demanded. The cornerstones of IPD diagnosis are clinical evaluation, laboratory characterization, and genetic testing. Achieving a diagnosis of IPD is desirable for several reasons, including the possibility of tailored therapeutic strategies and individual follow-up programs. However, detailed investigations can also open complex scenarios raising ethical issues in case of IPDs predisposing to hematological malignancies. This review offers an overview of IPD diagnostic workup, from the interview with the proband to the molecular confirmation of the suspected disorder. The main implications of an IPD diagnosis are also discussed.

show abstract

GATA1 gene variants associated with thrombocytopenia and anemia

Cited by 18 publications

References 20 publications

Recent advances in the understanding of transient abnormal myelopoiesis in Down syndrome

Recent advances in the understanding of transient abnormal myelopoiesis in Down syndrome

Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications

Diagnosing Inherited Platelet Disorders: Modalities and Consequences

Contact Info

Product

Resources

About