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

成人t细胞白血病/淋巴瘤（Adult T-cell leukemia/lymphoma， ATLL）是一种与人T-ceII白血病病毒I型（HTLV-I）相关的人类恶性肿瘤，其组织学通常为多形型，但组织学并不统一。为了明确组织学分型与预后的关系，特别是在ATLL中，并确认HTLV-I克隆整合的重要性，我们对572例淋巴结t细胞淋巴瘤进行了重新分类，并确认了t细胞表型和/或基因型。在所有病例中，使用Southern blot分析检测HTLV-I前病毒DNA在淋巴结中的克隆整合。此外，还进行了血清中抗atl抗原（ATLA）检测或淋巴结中HTLV-lpX扩增的PCR分析。然而，313例ATLA患者中有66例（21%）没有HTLV-I克隆整合的证据。572例分为3组；(A)有克隆整合者[247例]，(B)有ATLA者和无克隆整合者[66例]，(C)无ATLA者[259例]。组织学上，B组和C组多表现为大细胞型和AILD型，而a组多表现为多形性型。A组临床预后较B、c组差。结论确定A组为ATLL（HTLV-I相关t细胞淋巴瘤），B组为t细胞淋巴瘤，而t细胞淋巴瘤恰好发生在HTLV-I感染的携带者中。采用聚合酶链式反应原位杂交（PCR/ISH）和逆转录(RT)-PCR/ISH [RT-PCR/ISH]直接扩增HTLV-I DNA和tax/rex mRNA，探讨HTLV-I前病毒DNA与淋巴结表达的关系。我们研究了24例成人t细胞白血病/淋巴瘤（ATLL）、早期ATLL （I-ATLL）、HTJLV-I相关淋巴结炎皮肤病型（HAL-D）和增大的皮质旁型（HAL-EP）患者的淋巴结。在ATLL中，40-60%的有核细胞经PCR/ISH检测htlv - 1前病毒DNA阳性。而在I-ATLL和HAL中，阳性细胞分别为5-20%和1-5%以下。表达niRNA的细胞数量少于原病毒dna阳性的细胞数量。少

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