Association between ATL and non-hematopoietic neoplasms

A high incidence of multiple primary neoplasms has been observed in our patients with ATL in comparison to persons with other forms of hematologic malignancy who we have observed during the past 23 years (1963-1985). Five of 15 patients with ATL (33.3 per cent) have had at least one other associated neoplasm in comparison to only 44 of 1156 patients with other forms of hematological malignancy (3.8 per cent). The incidence figures for secondary neoplasms associated with the other hematologic malignancies were 4.3 per cent (16/370) for acute non-lymphocytic leukemia (ANLL), 2.2 per cent (2/90) for acute lymphocytic leukemia (ALL), 4.8 per cent (1/21) for acute unclassifiable leukemia, 2.2 per cent (5/225) for chronic myelogenous leukemia, 4.7 per cent (2/43) for chronic lymphocytic leukemia, 5.9 per cent (8/136) for malignant monoclonal gammopathy and 3.7 per cent (10/271) for malignant lymphoma. The incidence of multiple neoplasms in patients with ATL in comparison to those with other hematological malignancies was statistically significant (p < 0.01 or p < 0.001). The neoplasms associated with ATL have been adenocarcinoma of the thyroid or stomach, and squamous cell carcinoma of the larynx, lip or lung. We identified ATL-derived factor (ADF) in the cytoplasm of the secondary neoplasms of the ATL patients by means of indirect immunofluoroscopy and immunohistochemical techniques utilizing anti-ADF antibody. We also identified ras p21 products in these neoplasms by means of p21 ras monoclonal antibody studies. The possibility that HTLV-I was the cause of the secondary neoplasms thus was investigated. HTLV-I provirus genome was not found in all the six cases of non-ATL leukemic cells of the patients with anti-HTLV-I antibodies as determined by means of Southern blot analysis utilizing pX DNA probe. These findings suggest that there is some association between ATL cells and pre-malignant cells through ADF or other unknown factors in the activation of ras oncogenes. Subsequent suppression of host immune defence mechanisms in ATL patients permits evolution of the secondary neoplasms.