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（ATLL）是与人T细胞白血病病毒I型（HTLV-I）相关的人类恶性肿瘤，并且组织学通常指示多形性类型，但组织学不均匀。为阐明淋巴结T细胞淋巴瘤的组织学分型与预后的关系，特别是ATLL的组织学分型与预后的关系，并证实克隆性HTLV-Ⅰ整合的意义，我们对572例淋巴结T细胞淋巴瘤进行了重新分型，其中T细胞表型和/或基因型得到证实。在所有情况下，使用Southern印迹分析检查淋巴结中HTLV-I前病毒DNA的克隆整合。此外，还进行了血清中抗ATL抗原（ATLA）的检查或淋巴结中HTLV-lpX扩增的PCR分析。然而，313例ATLA患者中有66例（21%）没有克隆HTLV-I整合的证据。将572例患者分为3组：（A）有克隆整合的患者[247例]，（B）有ATLA的患者，和无克隆整合的患者。 ...更多信息 HTLV-1前病毒DNA阳性者66例，无ATLA阳性者259例。组织学上，B、C组多为大细胞型和AILD型，而A组多为多形性。A组临床预后较B组和C组差。总之，A组被确定为ATLL为探讨人嗜淋巴细胞病毒Ⅰ型（HTLV-Ⅰ）前病毒DNA与其在淋巴结中表达的关系，采用聚合酶链反应原位杂交（PCR/ISH）和逆转录（RT）-PCR/ISH [RT-PCR/ISH]直接扩增HTLV-Ⅰ DNA和Tax/雷克斯mRNA。我们研究了成人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）和皮质旁增大型（HAL-EP）患者的24个淋巴结。RT-PCR/ISH结果显示，ATLL中HTLV-1前病毒DNA阳性率为40-60%，I-ATLL和HAL中HTLV-1前病毒DNA阳性率分别为5- 20%和1-5%。mRNA表达的细胞数少于前病毒DNA阳性细胞数。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