Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome

Marianne E. Greene, Gina Mundschau, Joshua Wechsler, Michael McDevitt, Alan Gamis, Judith Karp, Sandeep Gurbuxani, Robert Arceci, John D. Crispino

Research output: Contribution to journalArticle

Abstract

Mutations in transcription factors often contribute to human leukemias by providing a block to normal differentiation. To determine whether mutations in the hematopoietic transcription factor GATA1 are associated with leukemia, we assayed for alterations in the GATA1 gene in bone marrow samples from patients with various subtypes of acute leukemia. Here we summarize our findings that GATA1 is mutated in the leukemic blasts of patients with Down syndrome acute megakaryoblastic leukemia (DS-AMKL). We did not find mutations in GATA1 in leukemic cells of DS patients with other types of acute leukemia, or in other patients with AMKL who did not have DS. Furthermore, we did not detect GATA1 mutations in DNAs from over 75 other patients with acute leukemia or from 21 healthy individuals. Since the GATA1 mutations were restricted to DS-AMKL, we also investigated whether GATA1 was altered in the "preleukemia" of DS, transient myeloproliferative disorder (TMD). TMD is a common myeloid disorder that affects 10% of DS newborns and evolves to AMKL in nearly 30% patients. We detected GATA1 mutations in TMD blasts from every infant examined. Together, these results demonstrate that GATA1 is likely to play a critical role in the etiology of TMD and DS-AMKL, and that mutagenesis of GATA1 represents a very early event in DS myeloid leukemogenesis. We hypothesize that disruption of normal GATA-1 function is an essential step in the initiation of megakaryoblastic leukemia in DS.

Original languageEnglish (US)
Pages (from-to)351-356
Number of pages6
JournalBlood Cells, Molecules, and Diseases
Volume31
Issue number3
DOIs
StatePublished - Nov 2003

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Leukemia, Megakaryoblastic, Acute
Myeloproliferative Disorders
Down Syndrome
Leukemia
Mutation
GATA1 Transcription Factor
Preleukemia
Mutagenesis
Transcription Factors
Bone Marrow
Newborn Infant
DNA
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology

Cite this

Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome. / Greene, Marianne E.; Mundschau, Gina; Wechsler, Joshua; McDevitt, Michael; Gamis, Alan; Karp, Judith; Gurbuxani, Sandeep; Arceci, Robert; Crispino, John D.

In: Blood Cells, Molecules, and Diseases, Vol. 31, No. 3, 11.2003, p. 351-356.

Research output: Contribution to journalArticle

Greene, ME, Mundschau, G, Wechsler, J, McDevitt, M, Gamis, A, Karp, J, Gurbuxani, S, Arceci, R & Crispino, JD 2003, 'Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome', Blood Cells, Molecules, and Diseases, vol. 31, no. 3, pp. 351-356. https://doi.org/10.1016/j.bcmd.2003.08.001
Greene, Marianne E. ; Mundschau, Gina ; Wechsler, Joshua ; McDevitt, Michael ; Gamis, Alan ; Karp, Judith ; Gurbuxani, Sandeep ; Arceci, Robert ; Crispino, John D. / Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome. In: Blood Cells, Molecules, and Diseases. 2003 ; Vol. 31, No. 3. pp. 351-356.
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