HTLV-I association between T-cell lymphoma and genomic changes in HTLV-I endemic areas

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Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-ceII leukemia virus type I (HTLV-I), and the histology usually indicates a pleomorphic type, but the histology is not uniform. To clarify the relation between the histological classification and prognosis, especially in ATLL, and to confirm the sigrnfcance of clonal HTLV-I integration, we reclassified 572 cases with nodal T-cell lyrnphoma, in which the T-cell phenotype and/or genotype was confirmed. In all cases, the clonal integration of HTLV-I proviral DNA in the lymph nodes was examined, using a Southern blot analysis. In addition, eithex an examination of anti-ATL antigen (ATLA) in the serum or a PCR analysis of HTLV-lpX amplification in lymph nodes was also performed. However, 66(21%) of 313 cases with ATLA had no evidence of clonal HTLV-I integration. 572 cases were classified into 3 groups ; (A) the cases with clonal integration [247 cases], (B) cases with ATLA, and those without clonal integrati … More on of HTLV-1 proviralDNA[66 cases], (C) cases without ATLA [259cases]. Histologically, groups B and C frequently demonstrated large cell type and AILD) type, however, group Atended to show a pleomorphic type. Group A clinically showed a poorer prognosis than groups B and C.In conclusion, group A was determined to be ATLL(HTLV-I associated T-cell lymphoma), while group B was T-cell lymphoma, which coincidently occurred in HTLV-I infected carriers.To examine the relationship between Human Tlymphotrophic virus type I (HTLV-I) proviral DNA and its expression in the lymph nodes, HTLV-I DNA and tax/rex mRNA directly were artiplified by polymerase chain reaction in situ hybridization (PCR/ISH), and reverse transcription (RT)-PCR/ISH [RT-PCR/ISH]. We studied 24 lymph nodes from patients with adult T-cell leukemia/lymphoma (ATLL), incipient ATLL (I-ATLL), and HTJLV-I associated lymphadenitis dermatopathic type (HAL-D) and enlarged paracortical type (HAL-EP). In ATLL, 40-60% of the nucleated cells were positive for HTLV-l proviral DNA by PCR/ISH.while in I-ATLL and HAL, 5-20%, and under 1-5% cells were positive, respectively. The number of niRNA expressed cells was smaller than that of the proviral DNA-positive cells. Less