Identification of biclonal (duplex) leukaemic cells expressing either CD4+/CD8- or CD4-/CD8+ from a patient with adult T-cell leukaemia/lymphoma.

Blood Transfusion Division, Miyazaki Medical College, Japan.
British Journal of Haematology (Impact Factor: 4.94). 04/1995; 89(3):669-71. DOI: 10.1111/j.1365-2141.1995.tb08387.x
Source: PubMed

ABSTRACT A 24-year-old Japanese woman was admitted to our hospital in 1987 with a chief complaint of skin eruptions, and was diagnosed as having chronic ATLL. In 1993 the leucocyte count increased gradually to 126.0 x 10(9)/l with 91.5% abnormal lymphocytes expressing two different types of antigenicity, either CD+/CD8- or CD4-/CD8+. Monoclonal integration of human T-cell lymphotropic virus type-I proviral DNA was detected at different sites of the genomic DNA in each cell type. These studies clearly indicate that CD4+/CD8- and CD4-/CD8+ leukaemic cells originated from two independent clones.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The association of CD26/dipeptidyl peptidase IV (DPPIV) and human T lymphotropic virus type I (HTLV-I) was studied by two approaches. First, we examined the expression of CD26 in peripheral blood mononuclear cells (PBMC) from the patients with adult T cell leukemia/lymphoma (ATLL), an HTLV-I-related malignancy. The expression of CD26 on the surface of PBMC was decreased in all 20 patients with ATLL compared with those from normal individuals (P < 0.01) and the expression of the CD26 gene transcript was not detectable in seven out of eight patients with ATLL. Then we compared the quantity of viral DNA in CD26-negative (CD26-) and CD26-positive (CD26+) cells obtained from 17 HTLV-I healthy carries by using a polymerase chain reaction method. The CD26-cells had a higher copy number of viral DNA than CD26+ cells. These findings indicate that HTLV-I has in vivo tropism to CD26- cells, suggesting that some phenotypes of ATLL cells reflect the in vivo cellular tropism of HTLV-I.
    Leukemia Research 04/1996; 20(4):357-63. · 2.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this review, we discuss the possible relationship between the clinical characteristics and the multiple integration of human T-cell lymphotropic virus type I (HTLV-I) proviral DNA in patients with adult T-cell leukemia/lymphoma (ATL). Some patients with ATL show multiple HTLV-I integrations and exhibit clinical characteristics unlike those of ATL patients who show the typical integration of a single provirus. Multiple HTLV-I integrations can be detected by Southern blotting as multiple bands having varied intensities. These multiple integration conditions can arise from one tumor cell clone carrying multiple copies of the provirus, or from multiple cell clones, each carrying one copy of the provirus. The former patients manifest an extremely aggressive clinical course with the infiltration of unusual organs such as the retina and uvea. The latter patients show an indolent clinical course with skin lesions. These findings suggest that the clinical implications for multiple HTLV-I integrations exist in ATL. This may be one of the explanations for the heterogeneous findings in the disease. Such observations may provide information linking viral integration with clinical manifestations, and improve our understanding of the pathogenesis of ATL.
    Leukemia and Lymphoma 10/1997; 27(1-2):43-51. · 2.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Many adult T-cell leukaemia/lymphoma (ATLL) patients who respond to induction treatment, then relapse. Knowing the clonality pattern of residual tumourous clones during treatment could help understand disease evolution and aid therapeutic decisions. We developed a sensitive and semi-quantitative molecular analysis of these clones in ATLL patients. DNA samples from PBMCs derived from eight ATLL patients were studied over time by quadruplicate linker mediated PCR (LMPCR) amplification of HTLV-1 integration sites. Patients were treated with combination chemotherapy, zidovudine-interferon-alpha and/or by peripheral stem cell transplantation or allogeneic bone marrow transplantation. Persistence of tumourous clones at a high frequency (>1/300 PBMCs) was frequently observed, even in complete responders, and was invariably correlated with relapse and/or poor outcome. Fluctuation in the frequency of some tumourous clones was observed with evidence for clonal change under treatment in one patient, indicating that treatment of ATLL can result in the selection of resistant clones. Finally, allogeneic bone marrow transplantation (BMT) using an HTLV-1 infected sibling as donor was found to be associated with long-lasting disappearance of tumourous clones and a possible cure of the disease. Long-term persistent clonal expansion of circulating HTLV-1 bearing T cells which derived from the donor bone marrow was evidenced in this patient. In conclusion, variable success in treatment of ATLL is probably due to the clonal heterogeneity which results in the selection of resistant clones. Semi-quantitative assessment of residual disease (RD) through LMPCR may predict treatment failure. Accordingly, additional therapy may be tailored to the clonality pattern observed after first-line therapy.
    British Journal of Haematology 07/1999; 105(3):743-51. · 4.94 Impact Factor