Incidence and clinical implications of GATA1 mutations in newborns with Down syndrome
- PMID: 17576817
- DOI: 10.1182/blood-2007-01-069542
Incidence and clinical implications of GATA1 mutations in newborns with Down syndrome
Abstract
Somatic mutations in the GATA1 gene are present in almost all cases of Down syndrome (DS)-associated acute megakaryoblastic leukemia (AMKL) and transient leukemia (TL). An in utero origin of the GATA1 mutation suggests it is an early leukemogenic event. To determine the detectable incidence and clinical relevance of GATA1 mutations in DS newborns, we screened Guthrie cards from 590 DS infants for mutations in the GATA1 gene. Twenty-two (3.8%) of 585 evaluable infants harbored a predicted functional GATA1 mutation; 2 were identified exclusively within intron 1. Hispanic newborns were 2.6 times more likely to have a mutated GATA1 gene than non-Hispanics (P = .02). Two newborns with a GATA1 mutation subsequently developed AMKL, and none of the infants without a functional GATA1 mutation were reported to have developed leukemia. In addition to screening for TL, a GATA1 mutation at birth might serve as a biomarker for an increased risk of DS-related AMKL.
Similar articles
-
GATA1 as a new target to detect minimal residual disease in both transient leukemia and megakaryoblastic leukemia of Down syndrome.Leuk Res. 2005 Nov;29(11):1353-6. doi: 10.1016/j.leukres.2005.04.007. Leuk Res. 2005. PMID: 15916804
-
Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome.Blood Cells Mol Dis. 2003 Nov-Dec;31(3):351-6. doi: 10.1016/j.bcmd.2003.08.001. Blood Cells Mol Dis. 2003. PMID: 14636651
-
Natural history of GATA1 mutations in Down syndrome.Blood. 2004 Apr 1;103(7):2480-9. doi: 10.1182/blood-2003-10-3383. Epub 2003 Dec 4. Blood. 2004. PMID: 14656875
-
Acute megakaryoblastic leukemia with acquired trisomy 21 and GATA1 mutations in phenotypically normal children.Eur J Pediatr. 2015 Apr;174(4):525-31. doi: 10.1007/s00431-014-2430-3. Epub 2014 Sep 30. Eur J Pediatr. 2015. PMID: 25266042 Review.
-
Down syndrome and malignancies: a unique clinical relationship: a paper from the 2008 william beaumont hospital symposium on molecular pathology.J Mol Diagn. 2009 Sep;11(5):371-80. doi: 10.2353/jmoldx.2009.080132. J Mol Diagn. 2009. PMID: 19710397 Free PMC article. Review.
Cited by
-
Myeloid leukemia in Down syndrome.Crit Rev Oncog. 2011;16(1-2):25-36. doi: 10.1615/critrevoncog.v16.i1-2.40. Crit Rev Oncog. 2011. PMID: 22150305 Free PMC article. Review.
-
Acute myeloid leukaemia at an early age: Reviewing the interaction between pesticide exposure and KMT2A-rearrangement.Ecancermedicalscience. 2017 Nov 30;11:782. doi: 10.3332/ecancer.2017.782. eCollection 2017. Ecancermedicalscience. 2017. PMID: 29225689 Free PMC article. Review.
-
Predispositions to Leukemia in Down Syndrome and Other Hereditary Disorders.Curr Treat Options Oncol. 2017 Jul;18(7):41. doi: 10.1007/s11864-017-0485-x. Curr Treat Options Oncol. 2017. PMID: 28580501 Review.
-
Clinical and biological aspects of myeloid leukemia in Down syndrome.Leukemia. 2021 Dec;35(12):3352-3360. doi: 10.1038/s41375-021-01414-y. Epub 2021 Sep 13. Leukemia. 2021. PMID: 34518645 Free PMC article. Review.
-
Precocious clonal hematopoiesis in Down syndrome is accompanied by immune dysregulation.Blood Adv. 2021 Apr 13;5(7):1791-1796. doi: 10.1182/bloodadvances.2020003858. Blood Adv. 2021. PMID: 33787858 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
