Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera.

Abstract

Indirect immunofluorescence of certain human sera demonstrated an antigen(s) in the cytoplasm of 1-5% of the cells of a T-cell line, MT-1, from a patient with adult T-cell leukemia (ATh), which is endemic in southwestern Japan. The antigen was not detected in other human lymphoid cell lines, including six T-cell lines, seven B-cell lines, and four non-T non-B cell lines. The antigen did not show cross antigenicity with that of herpesviruses, including Epstein-Barr virus, herpes simplex virus, cytomegalovirus, varicella-zoster virus, herpesvirus saimiri, and Marek disease virus. The proportion of antigen-bearing cells was increased by a factor of =5 on culture in the presence of 5-iodo-2'-deoxyuridine. Antibodies against the antigen in MT-I cells were found in all 44 patients with ATL examined and in 32 of 40 patients with malignant T-cell lymphomas (most of them had diseases similar to ATL except that leukemic cells were not found in the peripheral blood). The antibodies were also detected in 26% of the healthy adults examined from ATL-endemic areas but in only a few of those examined from ATL-non-endemic areas. On electron microscopy, extracellular type C virus particles were detected in pelleted MT-I cells cultured in the presence of5-iodo-2'-deoxyuridine. Recently, a probably new disease entity, adult T-cell leukemia (ATL), was proposed by Takatsuki and his co-workers (1, 2). Since then, many patients having ATL have been reported. These patients have been reported from a restricted area of southwestern Japan (3-7). This malignant disease has also been called adult T-cell leukemia/lymphoma (ATLL) because of its leukemic lymphoma nature. Its characteristic clinical and hematological features are: (i) onset in adulthood; (ii) acute or chronic leukemia with rapid progression; (iii) resistance to treatment with current antileukemic agents; (iv) appearance in peripheral blood of pleomorphic leukemic cells that have markedly deformed nuclei and T-cell surface markers; (v) frequent accompaniment by lymphadenopathy, hepatosplenomegaly, and hypercalcemia; (vi) absence of mediastinal tumor; and (vii) frequent skin lesions such as erythroderma and nodule formation (1)(2)(3)(4)(5)8).While studying the viral etiology ofthis malignancy, we found an antigen associated with a long-term cultured ATL cell line that is reactive with the sera of all the ATL patients tested and also with the sera of >25% ofhealthy adults from ATL-endemic areas but not with sera from those from nonendemic areas. We also detected type C virus particles in this cell line by electron microscopy.MATERIALS AND METHODS Cells. The MT-1 cell line derived from the peripheral blood of a patient having ATL (9) Sera. Sera was obtained from adult patients who have ATL or various other diseases and from healthy adults from both ATL-endemic and ATL-non-endemic areas (Fig. 1) The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734...

Viral epigenomes in human tumorigenesis

“…It was discovered in 1980 (Poiesz et al, 1980), and was associated with adult T-cell leukemia (ATL) shortly thereafter (Hinuma et al, 1981). At present, HTLV-1 is the only human retrovirus known to be directly associated with a human neoplasia.…”

Tax protein of HTLV-1 inhibits CBP/p300-mediated transcription by interfering with recruitment of CBP/p300 onto DNA element of E-box or p53 binding site

“…Human T-cell leukemia virus type 1 (HTLV-1) (Poiesz et al, 1980) is an etiologic agent of adult T-cell leukemia (ATL) (Hinuma et al, 1981;Yoshida et al, 1982). The virus-encoded regulatory protein Tax is critical for HTLV-1 replication and is thought to contribute to ATL development (Yoshida, 1993).…”

Titration of cellular export factors, but not heteromultimerization, is the molecular mechanism of trans-dominant HTLV-1 Rex mutants

“…The oncoretrovirus human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive malignancy of human CD4 + lymphocytes (Hinuma et al, 1981;Poiesz et al, 1980;Uchiyama, 1997;Yoshida et al, 1982). In addition, HTLV-1 has been associated with a chronic encephalomyelopathy known as tropical spastic paraparesis and HTLV-1-associated myelopathy (Gessain et al, 1985) or a form of cutaneous T-cell leukemia/ lymphoma (Poiesz et al, 1980;Yoshida et al, 1982).…”