HTLV-II and human lymphoproliferative disorders

J. D. Rosenblatt, I. S.Y. Chen, D. W. Golde

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

Human T-cell leukemia viruses (HTLV) types I and II are closely related human retroviruses associated with human lymphoid neoplasms. Although HTLV-I has been etiologically implicated in the adult T-cell leukemia/lymphoma (ATL) endemic to Japan and other regions of the world, the role of HTLV-II in human disease is still unclear. Recently, HTLV-II has been linked to less prevalent human lymphoproliferative disorders, including two unusual cases of hairy-cell leukemia. The HTLV-II virus was first identified in and molecularly cloned from the Mo T-cell line established from spleen cells from a patient with hairy-cell leukemia. The original patient's hematologic syndrome was typical of hairy-cell leukemia; he presented with pancytopenia, splenomegaly, and circulating tartrate-resistant acid phosphatase-positive (TRAP+) lymphoid cells with characteristic 'hairy' morphology. The disease process, however, proved to be atypical, in the the majority of the patient's circulating lymphoid cells formed rosettes with sheep erythrocytes and appeared to be of T-cell origin. In addition, the Mo T-cell line was TRAP+ and also formed E-rosettes, leading investigators to the conclusion that the patient had a T-cell variant of hairy-cell leukemia. Approximately 2 years ago, our laboratory isolated HTLV-II from a second patient with hairy-cell leukemia. The second patient, like his predecessor, had circulating TRAP+ abnormal lymphocytes, some with hairy-cell morphology. However, the TRAP+ hairy cells remained a minority population in the patient's peripheral blood. The majority of his peripheral blood lymphocytes, although morphologically atypical, were TRAP- and expressed T-cell markers, as determined by flow cytometry. His bone marrow was heavily infiltrated with TRAP+ hairy cells. We recently performed a postmortem study of the second patient's blood that demonstrated the presence of two coexisting clonal lymphoproliferative disorders (Rosenblatt, Blood, in press); one was of T-cell antigenic phenotype, and the other was of B-cell origin adn indistinguishable from typical hairy-cell leukemia. At autopsy, the patient's TRAP+ B cells were noted to have infiltrated the bone marrow and a variety of soft tissue, including the patient's liver and pleura. The atypical T cells circulating in the peripheral blood were found to contain oligoclonally integrated HTLV-II virus. The presence of oligoclonal HTLV-II provirus indicated that the peripheral blood (and, to a lesser degree, the bone marrow) contained an expanded T-cell clone derived from a single virally infected cell. The presence of oligoclonally integrated HTLV-II in the malignant T cells was strikingly similar to the monoclonally integrated HTLV-I typically seen in ATL. In contrast, relatively pure B-cell populations isolated either from the peripheral blood using cell fractionation techniques or the patient's pleural effusion were clonal, as determined by immunoglobulin gene rearrangement, but did not contain integrated HTLV-II virus. Therefore, in the second instance in which HTLV-II was found in association with hairy-cell leukemia, the virus appeared to be directly involved in genesis of the patient's T-cell malignancy, but only indirectly implicated in the coexisting B-cell hairy-cell leukemia.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalClinics in Laboratory Medicine
Volume8
Issue number1
DOIs
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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