Molecular‐genetic insights in paediatric T‐cell acute lymphoblastic leukaemia

Abstract

SummaryPaediatric T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy of thymocytes that accounts for about 15% of ALL cases and for which treatment outcome remains inferior compared to B-lineage acute leukaemias. In T-ALL, leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T-cells into uncontrolled cell growth and clonal expansion. This review provides an overview of the current knowledge on onco-and tumor suppressor genes in T-ALL and suggests a classification of these genetic defects into type A and type B abnormalities. Type A abnormalities may delineate distinct molecular-cytogenetic T-ALL subgroups, whereas type B abnormalities are found in all major T-ALL subgroups and synergize with these type A mutations during T-cell pathogenesis.

An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study

“…2,3 Despite the diversity of observed mutations and deletions, transcriptional microarray studies have consistently shown that T-ALL can be classified by five recurrent patterns of gene expression, namely the Immature/LYL1, TAL1, TLX1, TLX3 and HOXA clusters. [4][5][6] The last subgroup is characterized by aberrant activation of the HOXA gene locus on chromosome 7.…”

The relevance of PTEN-AKT in relation to NOTCH1-directed treatment strategies in T-cell acute lymphoblastic leukemia

“…6,7 We therefore proposed that these mutations should be classified as type B aberrations. 2 Type B mutations are prevalent among all T-ALL subtypes and affect a wide variety of cellular processes, including survival and proliferation, cell cycle progression, and epigenetic events. Type B mutations often affect signal transduction pathways, including the NOTCH1, IL7R-JAK-STAT, RAS-MEK-ERK, and PTEN-PI3K-AKT pathways.…”

DNA methylation pattern is altered in childhood T-cell acute lymphoblastic leukemia patients as compared with normal thymic subsets: insights into CpG island methylator phenotype in T-ALL

“…7 The analyzed genes have been selected based on their involvement in T-ALL pathogenesis as reported by others. 4,[8][9][10][11] Primer sequences are presented in Supplementary Table 1. On the basis of the number of hypermethylated genes patients were divided into CIMP þ and CIMP À groups.…”