In vitro infection of leukemic bone marrow with HTLV-I generates immortalized cell lines expressing T or myeloid cell phenotype

A. Giuliani, P. Vernole, S. D'Atri, G. Del Poeta, C. D'Onofrio, I. Faraoni, J. W. Greiner, E. Bonmassar, G. Graziani

Research output: Contribution to journalArticlepeer-review

Abstract

Leukemic bone marrow cells (> 90% blasts) of a patient with acute myeloblastic leukemia (AML), non-treated or pretreated in vitro with a mutagenic triazene compound, were infected with HTLV-I by coculture with irradiated virus donor cells. Immortalized, HTLV-I +, double-positive CD4/CD8 euploid T cell lines, expressing HLA class I/II monomorphic determinants, and inappropriate myeloid and progenitor cell markers tie CD13, CD14, CD15 and CD33 antigens) were obtained. In one out of 10 triazene-pretreated samples, HTLV-I infection resulted in the appearance of a rapidly growing triploid cell line (ie MTLC1 line) showing: (1) myeloid but not lymphoid phenotype; (2) beta and delta T cell receptor in germline configuration; (3) integrated, complete and incomplete HTLV-I provirus genome (also detected in a number of MTLC1 clones); (4) a high percentage of cells positive for non-specific cross-reacting antigen (a CEA-related molecule present on myeloid cells) under the influence of gamma-interferon; (5) absence of HLA class I/II antigen expression; (6) absence of tax gene transcription. Blast cell proliferation was marginal or absent when leukemic marrow was not subjected to retroviral infection. These results show that exposure of leukemic bone marrow to HTLV-I can be followed by immortalization of T and myeloid cells. Although no data are available to establish whether tax expression played a role in the early phase of the immortalization process of MTLC1 line, tax gene product was not required for maintaining long-term growth of MTLC1 cells.

Original languageEnglish
Pages (from-to)2071-2081
Number of pages11
JournalLeukemia
Volume9
Issue number12
Publication statusPublished - Dec 1995

Keywords

  • AML
  • Bone marrow
  • HTLV-I
  • Immortalization
  • Triazenes

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

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