Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy
Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy
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DOI：
10.1182/blood-2003-11-3944
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发表时间：
2004-12-15
期刊：
影响因子：
20.3
通讯作者：
Macintyre, E
中科院分区：
文献类型：
--
作者：
Asnafi, V;Beldjord, K;Macintyre, E
出生后胸腺退化在生命的前30年逐渐发生。它主要影响T细胞受体（TCR）字母表谱系前体，从而使多能胸腺前体成比例增加。我们发现，T-急性淋巴细胞白血病（TALLs）表现出类似的转变，随着年龄的增长，从主要TCR表达到成熟停滞的不成熟（IM 0/δ/γ）阶段。一半显示HOX 11，HOX 11 L2，SIL-TAL 1或CALM-AF 10失调，每一个都与特定的，与年龄无关的成熟停滞阶段相关。HOX 11和SIL-TAL代表α-谱系癌基因，而HOX 11 L2表达鉴定成熟停滞的中间α/γ-谱系阶段。与优先向上谱系退化一致，SIL-TAL 1和HOX 11 L2失调的发生率随年龄而降低。相比之下，HOX 11失调变得更加频繁，这表明潜伏期更长。TAL 1/LMO 1失调在T-ALL中更常见，主要是由于儿童中的SIL-TAL 1重排，但在青少年和成人中目前未知的机制。LMO 2与LYL 1的共表达频率高于TAL 1，主要见于IM 0/delta/gamma成人病例。这些年龄相关的表型和致癌途径的变化可能反映了胸腺人群恶性转化风险的进行性变化。(C)2004年，美国血液学会。
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 (TALLs) 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 up-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. (C) 2004 by The American Society of Hematology.