Elucidation of any mechanism underlying neoplastic proliferation is welcome news. The article by Qin et al was no exception.1 The authors have clearly demonstrated, as well as confirmed,2 that interleukin-7 (IL-7) and IL-15 regulate the expression of bcl-2 and c-mybgenes in cutaneous T-cell lymphoma (CTCL). It was disappointing to note, however, that Qin et al appear to be completely unaware of the underlying stimulus, which initiates the proliferation machinery in the first place. It has been recognized for some time that practically all patients with CTCL carry human T-cell lymphotropic virus–1 (HTLV-I) Tax in their circulating and skin-infiltrating lymphocytes.3,4 Such patients also have Tax mRNA and antibodies to p40 Tax, the gene product of this sequence.5,6 In addition, it has been shown that IL-15 overexpression is attributable, specifically, to Tax transactivation of its promoter, as well as other NFkB transcription factors (reviewed in Gitlin et al7). Therefore, while the data presented by Qin et al are not disputed, the report would have been more meaningful if the underlying cause for the upregulation of IL-7 and IL-15 had not been ignored. Such information not only is of cursory interest but also may have therapeutic implications since it has already been shown that the in vitro proliferation of CTCL cells can be inhibited with antisense to Tax.8
Why human T-cell lymphotropic virus–1 Tax is not the cause of cutaneous T-cell lymphoma
Dr Zucker-Franklin claims that the human T-cell lymphotropic virus–1 (HTLV-I) Tax protein is the main stimulus for mycosis fungoides (MF) and Sézary syndrome (SS), which are the main forms of cutaneous T-cell lymphoma (CTCL). But this view is not shared by the vast majority of the scientific community. Initially, in the early 1990s HTLV-I Tax DNA was reported to be present in 0% to 20% of CTCL cases, and only the Zucker-Franklin group reported numbers up to 95%.1-1
To settle the issue several groups checked their methods, and in 1996 and 1997 a number of papers appeared showing that the number of HTLV-I Tax–positive cases decreased in parallel to increased stringency of the polymerase chain reaction (PCR) conditions and the numbers of controls for the reagents used.1,2 All these studies indicated that HTLV-I Tax DNA is not present in MF and SS.
Even in Japan, where HTLV-I is endemic, no HTLV-I tax DNA could be detected in CTCL cells of MF and SS patients.1-4 Thus, to put it bluntly, HTLV-I Tax cannot be the main stimulus of MF or SS, as it is not present in the malignant or surrounding cells. But one cannot exclude that another virus (for example, an endogenous retrovirus, or ERV) is activated in CTCL cells and that these cells contain amplified DNA sequences that are similar to HTLV-I Tax sequences and proteins that crossreact with HTLV-I Tax.
Reasons for finding HTLV-I Tax DNA in CTCL are probably inadequate PCR conditions and misdiagnosis of CTCL. Patients with adult T-cell leukemia (ATL) often show skin lesions that resemble hypopigmented MF. Such a misdiagnosis occurred when the HUT78 and HUT102 cell lines were established.1-8 Both cell lines were initially described as SS and MF cell lines, respectively.1-9 But later it turned out that the patient from whom the HUT102 cell line had been derived died from ATL. Further examinations showed that HUT78 is a true SS cell line, whereas HUT102 is an HTLV-I–producing ATL cell line.1-10
