|Cancer : Adult T-cell leukemia/lymphoma (ATLL)|
|Cancer Name||Adult T-cell leukemia/lymphoma (ATLL)|
|Clinics and Pathology|
|Etiology||Pathogenesis of the ATLL is associated with HTLV-1 infection of the tumour clone in 100% of the cases. The interval between HTLV-1 infection and the onset of lymphoma is long (10-40 years) and only <5% of infected people actually develops the disease. HTLV-1 produces a trans-regulatory protein (Tax) inducing interleukin-2 (IL-2) and IL-2 receptor expression and consequent polyclonal CD4 cell growth. This T-cell population is at risk for the development of genetic and cytogenetic changes leading to lymphoma.
|Epidemiology||The disease affects adult people. Clusters were observed in Japan and in the Caribbean; sporadic cases were reported in Western countries.
|Pathology||The lymph node architecture is effaced by a diffuse proliferation of small and large lymphoid cells having pleomorphic cytological features. In the peripheral blood the neoplastic cells often display a lobated nucleus (flower cells); diffuse bone marrow infiltration is found in virtually all cases.
|Treatment||Multiagent chemotherapy usually attains only partial, short lasting responses. Highly active anti viral therapy with zidouvidine and interferon-alpha may be beneficial in some cases.
|Prognosis||Patients with aggressive disease usually survive less than 1 year; less than 10% of the patients survive more than 5 years. Longer survival (> 2 years) can be observed in rare patients presenting a chronic or a smouldering form.
|Description||From OMIM: "Itoh et al. (1991) isolated cDNAs encoding the human FAS antigen from a human T-cell lymphoma cDNA library. Sequence analysis predicted a 16-amino acid signal sequence followed by a mature protein of 319 amino acids with a single transmembrane domain and a molecular mass of approximately 36 kD. The FAS antigen shows structural homology with a number of cell surface receptors, including tumor necrosis factor (TNF) receptors (191190, 191191) and the low-affinity nerve growth factor receptor (NGFR; 162010). Northern blot analysis detected 2.7- and 1.9-kb FAS mRNAs in thymus, liver, ovary, and heart. Functional expression studies in mouse cells showed that the FAS antigen induced antibody-triggered apoptosis."|
|Cytogenetics Molecular|| Comparative genomic hybridization (CGH) studies revealed that the most frequent regions of DNA gains are located at 14q, 7q and 3p; whereas frequent losses involve sequences at 6q and 13q. Gain of 14q32 may be a recurrent specific abnormality in ATLL. Aggressive forms display more genomic aberrations than chronic forms. The number of chromosomal imbalances correlates with clinical outcome. Different hybridization patterns, suggesting clonal evolution, can be observed when analysing material from different sites or material taken at different time points in the same patient.
Upregulation of gene encoding for ribosomal proteins, proteosome subunits, translation factors was identified in acute vs chronic phases of the disease. Many of these genes are located in regions amplified by chromosome rearrangements. Downregulation of genes involved in immune response was also documented.
|Title||Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course.|
|Authors||Tsukasaki K, Krebs J, Nagai K, Tomonaga M, Koeffler HP, Bartram CR, Jauch A.|
|Citations||Blood 2001; 97: 3875-3881.|
|Title||Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki.|
|Authors||Itoyama T, Chaganti RS, Yamada Y, Tsukasaki K, Atogami S, Nakamura H, Tomonaga M, Ohshima K, Kikuchi M, Sadamori N.|
|Citations||Blood 2001; 97: 3612-3620.|
|Title||Genetic instability of adult T-cell leukemia/lymphoma by comparative genomic hybridization analysis.|
|Citations||J Clin Immunol 2002; 22: 57-63.|
|Title||Identifying progression-associated genes in adult T-cell leukemia/lymphoma by using oligonucleotide microarrays.|
|Authors||Tsukasaki K, Tanosaki S, DeVos S, Hofmann WK, Wachsman W, Gombart AF, Krebs J, Jauch A, Bartram CR, Nagai K, Tomonaga M, Said JW, Koeffler HP.|
|Citations||Int J Cancer 2004; 109: 875-881.|
|Title||The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis.|
|Authors||"Itoh, N.; Yonehara, S.; Ishii, A.; Yonehara, M.; Mizushima, S.-I.; Sameshima, M.; Hase, A.; Seto, Y.; Nagata, S."|
|Citations||"Cell 66: 233-243, 1991."|
|Source and Citation|
|Source||Atlas of Genetics and Cytogenetics in Oncology and Haematology|
|Citation|| Cuneo A, Castoldi GL . Adult T-cell leukemia/lymphoma (ATLL). Atlas Genet Cytogenet Oncol Haematol. May 2005 .
URL : http://AtlasGeneticsOncology.org/Anomalies/AdultTLeukLymphID2032.html