Human T cell lymphoma leukemia virus (HTLV) is a human retrovirus (RNA tumor virus) that was originally isolated from a few patients with leukemias or lymphomas involving mature T lymphocytes. Here we report that the serum of Japanese patients with adult T cell leukemia, but not the serum of tested normal donors, contains high titers of antibodies to HTLV. These observations, together with data from Japan showing that adult T cell leukemia is endemic in southwest Japan, suggest that HTLV is involved in a subtype of human T cell malignancy, including Japanese adult T cell leukemia.

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Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan (RNA tumor virus/type C virus/radioimmunoassays/Japanese adult T-cell leukemia/T-cell malignant lymphoma) ABSTRACTIn Japan, adult T-cell leukemias and lymphomas are more common than in the United States and Europe, and in the southwest part of Japan these T-cell malignancy cases appear in clusters. Therefore, we investigated the involvement in these leukemias and lymphomas of the human T-cell leukemia virus (HTLV) that was previously isolated in one of our laboratories from cultured T cells of some patients in the United States with leukemias and lymphomas involving relatively mature T cells. High titers of antibodies capable of quantitative precipitation of

We analyzed activating mutations of N-ras and K-ras by the polymerase chain reaction and oligonucleotide hybridization in hematological disorders. Activating mutations of these codons were detected in 4 of 20 cases of myelodysplastic syndrome (MDS) and 15 of 77 cases of acute myelogenous leukemia (AML). Out of 19 cases of MDS and AML who carried active mutations, 7 cases were found to have two or more distinct mutations in activating codons of N-ras and K-ras. Ras mutation was found preferentially in progressive disease such as refractory anemia with excess of blasts (RAEB) of RAEB in transformation (RAEB-t). A relatively high incidence of ras mutation was found in M₅ AML (40%). No ras mutations were found in other hematological disorders, such as acute lymphoblastic leukemia and chronic myelogenous-leukemia. The most frequent amino acid substitution was that of an aspartate for glycine at codon 12 of N-ras resulting from G to A mutation (11/35). The survival of AML patients who carried ras mutations showed no significant differences from those without ras mutations calculated by Kaplan-Meier. Seven cases of MDS and 7 cases of AML patients could be investigated at various points during their clinical course. Among these 14 cases, we found 2 interesting cases of MDS. The first case lost multiple clones carrying ras mutations during disease progression, the second case acquired mutation of the ras gene during disease progression. These results suggested that multiple point mutations of ras genes may not be initiating events but may contribute to a clonal evolution of MDS and AML.

Human T-cell lymphotrophic virus type I (HTLV-I) seroprevalence was 20% among Hawailan Japanese migrants (issei) and their offspring (nisei) from Okinawa compared to 35% in similarly aged men who were lifetime residents of Okinawa. A control group of migrants from a nonendemic area of Japan, Nligata, had low rates of HTLV-I antibodies, suggesting that Hawaiiperse is not an endemic area for HTLV-I. Factors that were significantly associated with