Analysis of GATA1 mutations and leukemogenesis in newborns with Down syndrome.

It has been reported that patients with Down syndrome (DS) frequently develop transient myeloproliferative disorder (TMD) and less commonly myeloid leukemia in DS (ML-DS). We examined the pathogenetic relationship of these conditions with somatic mutations of the GATA1 gene in children with both TMD and ML-DS. To determine the incidence of GATA1 mutations in a cohort of DS patients and the applicability of these mutations as a clonal marker to detect minimal residual disease, we screened 198 samples of 169 patients with DS for mutations in GATA1 exon 2 by direct sequencing. Novel mutations were detected in four of the 169 DS patients (2 with TMD and 2 with ML-DS). We examined spontaneous remission and response to therapy in TMD and ML-DS patients and concluded that these mutations can be used as stable markers in PCR analysis to monitor these events.

Molecular and chromosomal mutations among children with B-lineage lymphoblastic leukemia in Brazil's Federal District.

Acute lymphoblastic leukemia (ALL) accounts for approximately 80% of all acute leukemias during childhood. Chromosomal anomalies resulting from gene fusion, which are frequent in leukemias, create hybrid transcripts, the great majority of which encode transcription factors. We analyzed 88 pediatric patients (median age 7.3 years) who had B-lineage acute lymphoblastic leukemia (B-ALL), using reverse transcriptase-polymerase chain reaction, to look for gene fusion transcripts of TEL/AML1, E2A/PBX1, BCR/ABL p190, and MLL/AF4. The frequencies of these transcripts were 21.21, 9.68, 3.03, and 0%, respectively. All positive cases had a common B-ALL immunophenotype. The low frequency of the TEL/AML1 transcript that is found in developing countries, such as Brazil, may be due to the low incidence of leukemia; this would support Greaves' hypothesis.