GATA1 insufficiencies in primary myelofibrosis and other hematopoietic disorders: consequences for therapy

Te Ling, John D. Crispino, Maria Zingariello, Fabrizio Martelli, Anna Rita Migliaccio

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Introduction: GATA1, the founding member of a family of transcription factors, plays important roles in the development of hematopoietic cells of several lineages. Although loss of GATA1 has been known to impair hematopoiesis in animal models for nearly 25 years, the link between GATA1 defects and human blood diseases has only recently been realized. Areas covered: Here the current understanding of the functions of GATA1 in normal hematopoiesis and how it is altered in disease is reviewed. GATA1 is indispensable mainly for erythroid and megakaryocyte differentiation. In erythroid cells, GATA1 regulates early stages of differentiation, and its deficiency results in apoptosis. In megakaryocytes, GATA1 controls terminal maturation and its deficiency induces proliferation. GATA1 alterations are often found in diseases involving these two lineages, such as congenital erythroid and/or megakaryocyte deficiencies, including Diamond Blackfan Anemia (DBA), and acquired neoplasms, such as acute megakaryocytic leukemia (AMKL) and the myeloproliferative neoplasms (MPNs). Expert commentary: Since the first discovery of GATA1 mutations in AMKL, the number of diseases that are associated with impaired GATA1 function has increased to include DBA and MPNs. With respect to the latter, we are only just now appreciating the link between enhanced JAK/STAT signaling, GATA1 deficiency and disease pathogenesis.

Original languageEnglish
Pages (from-to)169-184
Number of pages16
JournalExpert Review of Hematology
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 4 2018

Fingerprint

Primary Myelofibrosis
Megakaryocytes
Diamond-Blackfan Anemia
Leukemia, Megakaryoblastic, Acute
Hematopoiesis
Deficiency Diseases
Neoplasms
Erythroid Cells
Hematologic Diseases
Cell Lineage
Transcription Factors
Therapeutics
Animal Models
Apoptosis
Mutation

Keywords

  • congenital anemias
  • erythropoiesis
  • GATA1
  • myelofibrosis
  • myeloproliferative disorders
  • ribosome deficiencies

ASJC Scopus subject areas

  • Hematology

Cite this

GATA1 insufficiencies in primary myelofibrosis and other hematopoietic disorders : consequences for therapy. / Ling, Te; Crispino, John D.; Zingariello, Maria; Martelli, Fabrizio; Migliaccio, Anna Rita.

In: Expert Review of Hematology, Vol. 11, No. 3, 04.03.2018, p. 169-184.

Research output: Contribution to journalReview article

Ling, Te ; Crispino, John D. ; Zingariello, Maria ; Martelli, Fabrizio ; Migliaccio, Anna Rita. / GATA1 insufficiencies in primary myelofibrosis and other hematopoietic disorders : consequences for therapy. In: Expert Review of Hematology. 2018 ; Vol. 11, No. 3. pp. 169-184.
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