Two groups of endogenous MMTV related retroviral env transcripts expressed in human tissues.

The human genome contains at least 50 copies of the human endogenous retrovirus K (HERV-K) family which is related to the mouse mammary tumor virus (MMTV). Some members have been shown to be transcriptionally active and to have large open reading frames. Using the RT-PCR method we have investigated the HERV-K env transcription pattern in several malignant tissues and in peripheral blood mononuclear cells PBMCs). Samples were derived from chronic myelogenous leukemia (CML), breast cancer, colon cancer, high and low grade non-Hodgkin's lymphomas, Hodgkin's disease, myelodysplastic syndrome, thyroid adenoma (TA) and from PBMCs of patients with breast cancer, gastric cancer, and of healthy individuals. We found abundant HERV-K env transcripts in all tissues under investigation. Using HERV-K 10 specific primers for amplification we detected in addition to transcripts with high homology to HERV-K 10 (ca. 96% homology on the amino acid level) also transcripts of low homology to HERV-K10 (ca. 71%). Interestingly, all solid tissues containing high percentages of malignant cells such as breast cancer, colon carcinoma, low and high grade non-Hodgkin's lymphomas showed exclusively HERV-K env related transcripts with low homology to HERV-K 10. In contrast, in samples containing only a low proportion of malignant cells or no malignant cells at all we observed both types of transcripts. Thus, our data suggest that the expression pattern of HERV-K elements in human cells is very heterogenous and subjected to a complex transcriptional regulation.

Therapeutic progress and comparative aspects in chronic myelogenous leukemia (CML): interferon alpha vs. hydroxyurea vs. busulfan and expression of MMTV-related endogenous retroviral sequences in CML. German CML Study Group.

In summary, it can be expected that the availability of unrelated donors will increase the number of CML patients that can be treated curatively with allogeneic BMT. Hydroxyurea has replaced busulfan as first line treatment in CML since it prolongs survival. Ongoing randomized studies comparing IFN-based treatment regimens with standard chemotherapy or IFN-monotherapy probably will answer the question whether IFN can cure a small percentage of CML patients and whether this small percentage can be increased by additional chemotherapy. The present attempts to improve prognostic scores and to apply them to early treatment decisions will allow treatment adaptation more individually. The implications of endogenous retroviral sequences expressed in CML cells are not known now, but may be far reaching.