The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1).The natural history of childhood ALL is almost entirely clinically silent and is well advanced at the point of diagnosis.
The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality among patients with childhood acute lymphoblastic leukaemia (ALL).
Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling.
In comparison with Western cohorts, the incidence of t(9;22) (q34;q11)/BCR-ABL (14.60%) in B-ALL and HOX11 expression in T-ALL (25.24%) seemed to be much higher in our group, while the incidence of t(12;21) (p13;q22)/ETV6-RUNX1 (15.34%) seemed to be lower in Chinese pediatric patients.
Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL.
The ETV6/RUNX1 (E/R) gene fusion is generated by the t(12;21) and found in approximately 25% of childhood B-cell precursor acute lymphoblastic leukemia.
In this cohort of Taiwanese children, the relative frequencies of the 4 translocations of B-lineage ALL were 8% with ALL-type t(9;22)/BCR-ABL1, 4% with (1;19)/TCF-PBX1, 2% with t(4;11)/MLL-AF4, and 17.6% with t(12;21)/ETV6-RUNX1.
The assigned risk groups/treatment modalities for the 171 (25%) patients with t(12;21)-positive ALLs were 74 (43%) standard risk, 71 (42%) intermediate risk and 26 (15%) high risk.
This series of DS leukemias-the largest to date-reveals that DS-ALL is a heterogeneous disorder that comprises both t(12;21) and HeH as well as DS-related abnormalities.
The modal chromosome numbers, incidence, types, and numbers of additional abnormalities, genomic imbalances, and chromosomal breakpoints in the 245 karyotypically informative cases, as well as in 152 previously reported cytogenetically characterized t(12;21)-positive ALLs in the same age group, were ascertained.
Minimal residual disease analysis in children with t(12;21)-positive acute lymphoblastic leukemia: comparison of Ig/TCR rearrangements and the genomic fusion gene.
The importance of RUNX1 in B-cell development is additionally demonstrated by its dysregulation in the t(12;21) translocation, which is the most frequent translocation found in acute lymphocytic leukemia.
Further research is needed to explore whether the 2 to 7 years age incidence peak in childhood ALL harbor yet unidentified cytogenetic subsets with the same natural history as the high-hyperdiploid and t(12;21)-positive leukemias.
Prospective gene expression analysis accurately subtypes acute leukaemia in children and establishes a commonality between hyperdiploidy and t(12;21) in acute lymphoblastic leukaemia.
The fusion protein TEL-AML1 in t(12;21)+ acute lymphoblastic leukemia (ALL) recruits co-repressors and histone deacetylases (HDAC), which transrepress AML1 target genes.