Adult T-cell leukemia

Adult T-cell leukemia (ATL) is one of the most aggressive hematologic malignancies and is caused by human T-cell leukemia virus type 1 (HTLV-1). The HTLV-1 Tax protein has been demonstrated to be the oncogenic protein of the virus. Tax may contribute to the process of carcinogenesis by a variety of mechanisms, including upregulating the expression of cellular genes involved in T cell growth and proliferation, including IL-2, IL-2R-alpha, and IL-15. However, ATL cells do not always need Tax expression in the later stage of leukemogenesis. Genetic and epigenetic changes should be implicated in such multistep leukemogenesis. Regarding genetic changes, mutation of p53, and deletion of p16 have been reported in ATL. Mutations of Fas gene are also reported in patients with ATL cells. However, such genetic changes were not frequently detected. In this regard, epigenetic change of p16/INK4A gene was more frequent in ATL cells, and accumulated according to the disease progression. This finding suggests that epigenetic change, including DNA methylation, plays an important role in the leukemogenesis of ATL.

Cancer; Viral infectious disease

nt06160 Human T-cell leukemia virus 1 (HTLV-1)
nt06507 TGFB signaling
nt06516 TNF signaling
nt06518 JAK-STAT signaling
nt06537 TCR/BCR signaling

p53 (mutation) [HSA:7157] [KO:K04451]
p16/INK4A (deletion, promoter methylation) [HSA:1029] [KO:K06621]
Fas (mutation) [HSA:355] [KO:K04390]

Human T-lymphotropic virus 1 [GN:T40003]

PMID:12910250

PMID:14686488

PMID:10190897

PMID:17387298

PMID:16362996