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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy.

Postnatal thymic involution occurs progressively throughout the first 3 decades of life. It predominantly affects T-cell receptor (TCR) alphabeta-lineage precursors, with a consequent proportional increase in multipotent thymic precursors. We show that T-acute lymphoblastic leukemias (T-ALLs) demonstrate a similar shift with age from predominantly TCR expressing to an immature (IM0/delta/gamma) stage of maturation arrest. Half demonstrate HOX11, HOX11L2, SIL-TAL1, or CALM-AF10 deregulation, with each being associated with a specific, age-independent stage of maturation arrest. HOX11 and SIL- TAL represent alphabeta-lineage oncogenes, whereas HOX11L2 expression identifies an intermediate alphabeta/gammadelta-lineage stage of maturation arrest. In keeping with preferential alphabeta-lineage involution, the incidence of SIL-TAL1 and HOX11L2 deregulation decreased with age. In contrast, HOX11 deregulation became more frequent, suggesting longer latency. TAL1/LMO1 deregulation is more frequent in alphabeta-lineage T-ALL, when it is predominantly due to SIL-TAL1 rearrangements in children but to currently unknown mechanisms in adolescents and adults. LMO2 was more frequently coexpressed with LYL1, predominantly in IM0/delta/gamma adult cases, than with TAL1. These age-related changes in phenotype and oncogenic pathways probably reflect progressive changes in the thymic population at risk of malignant transformation.[1]


  1. Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy. Asnafi, V., Beldjord, K., Libura, M., Villarese, P., Millien, C., Ballerini, P., Kuhlein, E., Lafage-Pochitaloff, M., Delabesse, E., Bernard, O., Macintyre, E. Blood (2004) [Pubmed]
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