NEW YORK (Reuters Health) - Mutations in GATA1, an erythroid/megakaryocyte transcription factor gene, can be documented in most Down syndrome children who develop either transient myeloproliferative disorder or acute megakaryoblastic leukemia, as well as in some Down syndrome patients who have not yet developed clinical signs of these diseases.
In a multicenter study in the U.K., researchers assayed genomic DNA extracted from peripheral blood samples, neonatal blood spots, or bone marrow from 12 Down syndrome infants with acute megakaryoblastic leukemia, 4 with transient myeloproliferative disorder, and 21 with no clinical signs of either disease. Assays were also performed on DNA extracted from the cord blood of 62 babies without Down syndrome.
In the April 1 issue of Blood, senior author Dr. Paresh Vyas of John Radcliffe Hospital in Oxford, England reports with his colleagues that all of the Down syndrome babies with the clonal disorders had GATA1 mutations. Four of the babies with acute megakaryoblastic leukemia had multiple independent mutations.
In addition, according to the article, mutations were present at birth in 3 of 4 children "...without clinical transient myeloproliferative disorder, who later developed acute megakaryoblastic leukemia.”
Mutations were also present at birth “in 2 of 21 Down syndrome neonates who have not yet, but could still, develop acute megakaryoblastic leukemia (now 26 and 31 months).”
No GATA1 mutations could be documented in the cord blood samples from the 62 babies without Down syndrome.
“These data show GATA1 mutations occur in utero in most Down syndrome (patients with these disorders), that they may occur without clinical signs of disease, and that multiple separate GATA1 mutant clones can occur in an individual,” the investigators conclude.
In an accompanying editorial, Dr. Jeffrey W. Taub of Children’s Hospital of Michigan in Detroit, Michigan, praises the researchers’ approach of analyzing neonatal blood spots stored on so-called Guthrie cards. These cards, he says, "...are an invaluable repository of archival blood specimens to identify the presence of diseases in newborns.”
Dr. Taub adds, “If it is clearly demonstrated (in large trials) that GATA1 mutations can exist in Down syndrome newborns...who are at risk for the development of acute megakaryoblastic leukemia, an intriguing concept could involve early interventions...to eliminate the clones containing the mutation and potentially prevent the subsequent development of (the disease).”
Source: Blood 2004; 103:2434,2480-2489 [ Google search on this article ]
MeSH Headings:Myeloproliferative DisordersCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
