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.
Asnafi
Vahid
V
Necker-Enfants-Malades and Trousseau, Assistance Publique-Hopitaux de Paris, INSERM EMIU210 and Université Paris V, Hôpital Purpan, Toulouse, France.
Beldjord
Kheira
K
Libura
Marta
M
Villarese
Patrick
P
Millien
Corrine
C
Ballerini
Paola
P
Kuhlein
Emilienne
E
Lafage-Pochitaloff
Marina
M
Delabesse
Eric
E
Bernard
Olivier
O
Macintyre
Elizabeth
E
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001284:Atrophy; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D006801:Humans; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009857:Oncogenes; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000473:pathology*
D017931:DNA Primers