Correspondence

HTLV tax and Mycosis Fungoides

N Engl J Med 1993; 329:580August 19, 1993

Article

To the Editor:

Although a causal relation between human T-cell lymphotropic retrovirus type I and type II (HTLV-I and HTLV-II) and adult T-cell leukemia has been well established, the association between HTLVs and the cutaneous T-cell neoplasm mycosis fungoides has remained controversial. Few patients with mycosis fungoides are seropositive for antibodies to structural components of HTLV I and II virions; a typical figure is about 15 percent. When HTLV-I- or HTLV-II-related proviral DNA sequences have been detected, they have often been found to be incomplete1-3. Nonetheless, cultures of peripheral-blood mononuclear cells from the majority of patients with mycosis fungoides produce retrovirus-like particles indistinguishable ultrastructurally from HTLV-I or HTLV-II1,2. Such particles have not been seen in cultures of mononuclear cells from healthy volunteers. In addition, proviral sequences homologous with several regions of HTLV-I or HTLV-II have been detected in a number of cultures by means of DNA amplification1-3. Because of the caveat that some of these sequences may represent human endogenous retroviruses,4 we have initiated a survey using the polymerase chain reaction (PCR) with Southern blot analysis to probe for HTLV-I or HTLV-II tax in freshly isolated mononuclear cells from patients with mycosis fungoides. Thus far, tax -- the putative transforming gene for these viruses5 -- has not been shown to share homology with any human DNA sequences.

Peripheral-blood mononuclear cells from 29 patients and 6 healthy volunteers were isolated, and cell lysates were processed1,2,6. Prototypic HTLV-I and HTLV-II cell lines, C91/PL and MoT, served as positive controls. PCR and Southern blotting were performed as previously described,1,2 with HTLV-tax-specific primers for SK43 and SK44 and probe SK45 (Perkin Elmer-Cetus, Norwalk, Conn.). Probe labeling and detection of bound probe were carried out with Genius kits 3 and 6 (Boehringer-Mannheim, Indianapolis). Southern blotting of the PCR products of mononuclear cells isolated from 19 of the 29 patients, but not from any of the 6 volunteers, showed 159-bp bands that comigrated with those of the positive controls (Figure 1Figure 1Southern Blot of HTLV-tax-Related PCR Products Amplified from Lysates of Fresh Peripheral-Blood Mononuclear Cells from Patients with Mycosis Fungoides.). Samples prepared from the volunteers showed no detectable bands, as in our previous studies, in which we searched for other HTLV-I and HTLV-II sequences1,2.

About two thirds of the patients with mycosis fungoides in our present study appeared to be infected with HTLV-I or HTLV-II, since their circulating mononuclear cells contained HTLV-related tax sequences. This may be relevant to the pathogenesis of this neoplasm. The absence of antibodies to HTLV-I or HTLV-II in most of these patients is puzzling. It could be attributed to the limited antigenic spectrum of commercially available reagents, which include virus structural proteins but not the tax protein. It may also reflect an impaired immune response of patients in whom mycosis fungoides develops rather than adult T-cell leukemia. Other investigators have suggested that genetic variation in the immune response may account for the development of tropical spastic paraparesis and HTLV-associated myelopathy instead of adult T-cell leukemia in people infected with HTLV-I7.

Bette A. Pancake, Ph.D.
Dorothea Zucker-Franklin, M.D.
New York University Medical Center, New York, NY 10016

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   Kensuke Kojima, Masamichi Hara, Takashi Sawada, Akira Miyata, Hiroyuki Saito, Yoshinobu Matsuo, Masaki Yasukawa, Shigeru Fujita, Mine Harada. (2000) Human T-Lymphotropic Virus Type I Provirus and T-Cell Prolymphocytic Leukemia. Leukemia & Lymphoma 38:3-4, 381-386
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   Kensuke Kojima, Takashi Sawada, Masaki Yasukawa, Yoshinubu Matsuo, Yoshihiro Yakushijin, Hiroshi Narumi, Taichi Azuma, Hidetaka Takimoto, Masamichi Hara. (1998) Deleted HTLV provirus in peripheral blood cells of a patient with T-cell prolymphocytic leukaemia. British Journal of Haematology 100:3, 567-570
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   Gary S. Wood, Anupama Salvekar, John Schaffer, Carol F. Crooks, Will Henghold, David P. Fivenson, Youn H. Kim, Bruce R. Smoller. (1996) Evidence Against a Role for Human T-Cell Lymphotrophic Virus Type I (HTLV-I) in the Pathogenesis of American Cutaneous T-Cell Lymphoma.. Journal of Investigative Dermatology 107:3, 301-307
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6. 6

   Alejandro Vallejo, José L. López-Estebaranz, Pablo Ortiz-Romero, Alfredo García-Sáiz. (1995) Is Mycosis fungoides Associated with HTLV-I?. Vox Sanguinis 69:1, 84-84
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7. 7

   GIANGUGLIELMO ZEHENDER, LUCA MERONI, STEFANIA PICONI, CHIARA DE MADDALENA, CARLO PARRAVICINI, MARIO CLERICI, ANNA L. RIDOLFO, MAURO MORONI, MASSIMO GALLI. (1995) Frequent Detection of Antibodies against HTLV Antigens in Patients with AIDS-Related Non-Hodgkin Lymphoma. AIDS Research and Human Retroviruses 11:7, 823-827
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8. 8

   DOROTHEA ZUCKER-FRANKLIN, BETTE A. PANCAKE, ALVIN E. FRIEDMAN-KIEN. (1994) Cutaneous Disease Resembling Mycosis Fungoides in HIV-Infected Patients Whose Skin and Blood Cells Also Harbor Proviral HTLV Type I. AIDS Research and Human Retroviruses 10:9, 1173-1177
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9. 9

   (1993) More on HTLV tax and Mycosis Fungoides. New England Journal of Medicine 329:27, 2035-2036
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10. 10

    Douglas Grossman, Madeleine Duvic. (1993) Cutaneous T-cell lymphoma after blood transfusion. The Lancet 342:8885, 1483
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