Entry

H00009                      Disease

Name

Adult T-cell leukemia

Description

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.

Category

Cancer

Brite

Human diseases [BR:br08402]
Cancers
  Cancers of haematopoietic and lymphoid tissues
   H00009  Adult T-cell leukemia
Infectious diseases [BR:br08401]
Viral infections
  Infections caused by ssRNA-RT viruses
   H00009  Adult T-cell leukemia
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
  Neoplasms of haematopoietic or lymphoid tissues
   Mature T-cell or NK-cell neoplasms
    2A90  Mature T-cell lymphoma, specified types, nodal or systemic
     H00009  Adult T-cell leukemia
Tumor markers [br08442.html]
H00009

Pathway

hsa05166

Human T-cell leukemia virus 1 infection

Network

nt06114  PI3K signaling (viruses)
nt06119  JAK-STAT signaling (viruses)
nt06120  Calcium signaling (viruses and bacteria)
nt06123  TNF signaling (viruses and bacteria)
nt06129  MHC presentation (viruses)
nt06130  Cell cycle (viruses)
nt06140  Transcription (viruses)
nt06150  Cytokine-cytokine receptor interaction (viruses)
nt06160  Human T-cell leukemia virus 1 (HTLV-1)
nt06507  TGFB signaling

Gene

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

Pathogen

Human T-lymphotropic virus 1 [GN:T40003]

Other DBs

ICD-11:

2A90.5

ICD-10:

C91.5

MeSH:

D015459

Reference

PMID:12910250

Authors

Matsuoka M

Title

Human T-cell leukemia virus type I and adult T-cell leukemia.

Journal

Oncogene 22:5131-40 (2003)
DOI:10.1038/sj.onc.1206551

Reference

PMID:14686488

Authors

Yasunaga J, Matsuoka M

Title

Leukemogenesis of adult T-cell leukemia.

Journal

Int J Hematol 78:312-20 (2003)
DOI:10.1007/BF02983555

Reference

PMID:10190897

Authors

Maeda T, Yamada Y, Moriuchi R, Sugahara K, Tsuruda K, Joh T, Atogami S, Tsukasaki K, Tomonaga M, Kamihira S.

Title

Fas gene mutation in the progression of adult T cell leukemia.

Journal

J Exp Med 189:1063-71 (1999)
DOI:10.1084/jem.189.7.1063

Reference

PMID:17387298

Authors

Yasunaga J, Matsuoka M.

Title

Human T-cell leukemia virus type I induces adult T-cell leukemia: from clinical aspects to molecular mechanisms.

Journal

Cancer Control 14:133-40 (2007)
DOI:10.1177/107327480701400206

Reference

PMID:16362996

Authors

Jarrett RF.

Title

Viruses and lymphoma/leukaemia.

Journal

J Pathol 208:176-86 (2006)
DOI:10.1002/path.1905

DISEASE: Adult T-cell leukemia