Review on Adult T-cell leukemia/lymphoma (ATLL), with data on clinics, and the genes involved

Castoldi, GL

Cuneo, A

Atlas of Genetics and Cytogenetics in Oncology and Haematology

I-Revues

   
 
 
 
 
 
Leukaemia Section 
Mini Review 
 
Atlas Genet Cytogenet Oncol Haematol. 2005; 9(3)  
 
236 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
OPEN ACCESS JOURNAL AT INIST-CNRS 
Adult T-cell leukemia/lymphoma (ATLL) 
Antonio Cuneo, Gianluigi Castoldi 
Hematology Section, Department of Biomedical Sciences, University of Ferrara, Corso Giovecca 203, 
Ferrara, Italy (AC, GC) 
 
Published in Atlas Database: May 2005 
Online updated version: http://AtlasGeneticsOncology.org/Anomalies/AdultTLeukLymphID2032.html 
DOI: 10.4267/2042/38215 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2005 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Clinics and pathology 
Phenotype/cell stem origin 
This is a T-cell lymphoid neoplasia caused by HTLV1 
infection. The phenotype is CD3+, CD5+, CD7- with 
positivity for the CD4 and CD25 molecules in the 
majority of the cases. 
Etiology 
Pathogenesis of the disease: 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. 
Clinics 
The disease usually runs an aggressive course, with 
peripheral blood and bone marrow involvement, diffuse 
adenopathies, hepatomegaly, bone lesions and 
hypercalcemia. Smouldering or chronic forms were 
also observed. 
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. 
Cytogenetics 
Note 
The karyotype almost invariably shows a high degree 
of complexity and variability. Aneuploidy and more 
than 6 chromosome breaks were observed in the 
majority of cases. The most frequent gains include 
trisomy 3, trisomy 8, trisomy 9 and trisomy 21; 
monosomies involve chromosome 4, 8, 10 and 22. 
Breakpoints clusters are found at 1p and 1q, at 3q, 6q, 
7q, 10p, 12q, 13q, 14q, 17p and 21p. Multiple breaks 
and aberrations of some of these chromosome regions 
may predict for an inferior outcome. 
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  
Adult T-cell leukemia/lymphoma (ATLL) Cuneo A, Castoldi GL 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2005; 9(3)  
 
237 
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. 
References 
Itoyama T, Chaganti RS, Yamada Y, Tsukasaki K, Atogami S, 
Nakamura H, Tomonaga M, Ohshima K, Kikuchi M, Sadamori 
N. 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. Blood. 
2001 Jun 1;97(11):3612-20 
Tsukasaki K, Krebs J, Nagai K, Tomonaga M, Koeffler HP, 
Bartram CR, Jauch A. Comparative genomic hybridization 
analysis in adult T-cell leukemia/lymphoma: correlation with 
clinical course. Blood. 2001 Jun 15;97(12):3875-81 
Tsukasaki K. Genetic instability of adult T-cell 
leukemia/lymphoma by comparative genomic hybridization 
analysis. J Clin Immunol. 2002 Mar;22(2):57-63 
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. Identifying progression-
associated genes in adult T-cell leukemia/lymphoma by using 
oligonucleotide microarrays. Int J Cancer. 2004 May 
10;109(6):875-81 
This article should be referenced as such: 
Cuneo A, Castoldi GL. Adult T-cell leukemia/lymphoma 
(ATLL). Atlas Genet Cytogenet Oncol Haematol. 2005; 
9(3):236-237. 


Adult T-cell leukemia/lymphoma (ATLL)

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Adult T-cell leukemia/lymphoma (ATLL)

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