Korean J Hematol.  2008 Mar;43(1):43-47. 10.5045/kjh.2008.43.1.43.

GATA1 Mutation in Transient Myeloproliferative Disorder of Down Syndrome

• Ha JS
• Lee WM
• Kim JH
• Ryoo NH
• Jeon DS
• Kim JR
• Kim HS
• Choi BK

• KMID: 1485156
• DOI: http://doi.org/10.5045/kjh.2008.43.1.43

Abstract

Children with Down syndrome (DS) have a higher risk of developing leukemia than do healthy children, and they especially have a higher risk for developing transient myeloproliferative disorder (TMD) or acute megakaryocytic leukemia (AMKL). In recent studies, it has been reported that most of these patients have acquired mutation of the GATA1 gene, which encodes the erythroid/megakaryocytic transcription factor GATA1. GATA1 mutations have not been found in AMKL patients who did not have DS and other hematologic malignancies in DS. Most of the GATA1 mutations in DS-TMD/AMKL are nonsense mutations that are mainly located in exon 2. We observed a nonsense mutation in exon 2 of GATA1 [c.189_190delCA (Tyr63X)] in one case of DS-TMD. The GATA1 mutation has been thought to be an early event in the leukemogenesis of DS-TMD/AMKL and it could be used as a stable molecular marker to assess the treatment response or to monitor for the recurrence of DS-TMD/AMKL.

Keyword

GATA1; Down syndrome; Transient myeloproliferative disorder

MeSH Terms

Child
Codon, Nonsense
Down Syndrome
Exons
GATA1 Transcription Factor
Hematologic Neoplasms
Humans
Leukemia
Leukemia, Megakaryoblastic, Acute
Myeloproliferative Disorders
Organothiophosphorus Compounds
Recurrence
Codon, Nonsense
Down Syndrome
GATA1 Transcription Factor
Myeloproliferative Disorders
Organothiophosphorus Compounds

Figure

• 

  Fig. 1 Bone marrow aspiration smear showing increased immature cells which have less condensed coarse chromatin and cytoplasmic blebbing (Wright-Giemsa stain, ×1,000).

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  Fig. 2 Direct sequence analysis of exon 2 of GATA1 gene. Wild-type (WT) trace is shown above the patient result for comparison. Note there are two superimposed sequence traces in patient result. Thesu-perimposed traces are wild type and mutant type which has deletion of CA (rectangular) from nucleotides 189 to 190 (c.189_190delCA). This mutation is a nonsense mutation that codon 63 TAC was changed to stop codon TAG.

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