Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course.
Sixty-four patients with adult T-cell leukemia/lymphoma (ATL; 18 patients with indolent subtype and 46 with aggressive subtype) associated with human T-lymphotropic virus type 1 (HTLV-1) were analyzed using comparative genomic hybridization (CGH). The most frequent observations were gains at chromosomes 14q, 7q, and 3p and losses at chromosomes 6q and 13q. Chromosome imbalances, losses, and gains were more frequently observed in aggressive ATL than in indolent ATL, with significant differences between the 2 ATL subtypes at gains of 1q and 4q. An increased number of chromosomal imbalances was associated with a significantly shorter survival in all patients. A high number of chromosomal losses was associated with a poor prognosis in indolent ATL, whereas the presence of 7q+ was marginally associated with a good prognosis in aggressive ATL. Paired samples (ie, samples obtained at different sites from 4 patients) and sequential samples from 13 patients (from 6 during both chronic disease and acute crisis and from 7 during both acute onset and relapse) were examined by CGH and Southern blotting for HTLV-1. All but 2 paired samples showed differences on CGH assessment. Two chronic/crisis samples showed distinct results regarding both CGH and HTLV-1 integration sites, indicating clonal changes in ATL at crisis. In 11 patients, the finding of identical HTLV-1 sites and clonally related CGH results suggested a common origin of sequential samples. In contrast to chronic/crisis samples, CGH results with all acute/relapse sample pairs showed the presence of clonally related but not evolutional subclones at relapse, thereby suggesting marked chromosomal instability. In summary, clonal diversity is common during progression of ATL, and CGH alterations are associated with clinical course. (Blood. 2001;97:3875-3881)
Tsukasaki
K
K
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA. tsukasak@net.nagasaki-u.ac.jp
Krebs
J
J
Nagai
K
K
Tomonaga
M
M
Koeffler
H P
HP
Bartram
C R
CR
Jauch
A
A
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D007564:Japan; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D016662:Virus Integration
D004279:DNA, Viral