Random integration of HTLV-I provirus; increasing chromosomal instability

Adult T-cell leukemia/lymphoma (ATLL) is a neoplasm of mature helper (CD4) T-lymphocytes. Human T-cell lymphotropic virus type-I (HTLV-T) is etiologic ally considered to cause ATLL. It has been suggested that HTLV-I integrates its provirus into random sites in host chromosomal DNA after infection. Cl onal integration has been observed in patients with ATLL, including smolder ing, chronic and acute leukemia states, Almost all cases with ATLL demonstr ate clonal chromosome abnormalities, with karyotypes being very complicated in both number and structure. However, there are no specific karyotype abn ormalities in ATLL. In order to examine the role of HTLV-I in the pathogene sis of ATLL, we investigated whether or not HTLV-I randomly integrates and whether the integration site in the human genome is associated with any chr omosomal abnormality. We analyzed 18 cases with ATLL, which included 15 cas es with acute states, two cases with chronic states and one case with a smo ldering state. In four of the 18 cases, the HTLV-I provirus integrated into the 9th chromosome, while in three cases, it integrated into the ist or 10 th chromosome. However, the integrated site in the chromosome varied in eac h case and the random integration was considered to be true. All 15 cases w ith acute ATLL had complicated chromosomal abnormalities and two cases with chronic and smoldering ATLL showed simple abnormal karyotypes, while one c ase with chronic ATLL showed a normal karyotype. In 15 of the 18 cases, the chromosomes with HTLV-I integration showed abnormalities. In particular, i n two cases with simple chromosome abnormalities, HTLV-I integrated into th e abnormal chromosome, but not into the normal chromosome. The HTLV-I provi ral integration thus seems to be associated with chromosome abnormalities. In the multistage leukemogenesis of ATLL, these findings indicate that HTLV -I integration might play an important role in the induction of chromosomal instability. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.