PubMed · 6902695
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G Grillet. 1980. [Anemia].. https://pubmed.ncbi.nlm.nih.gov/6902695/
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Retrovirus-mediated gene transfer was used to study the effects of dysregulated expression of the zinc-finger transcription factor, GATA-1, which has been shown to be required for erythropoiesis. A retroviral vector (PGK-GATA-1) was constructed with the murine GATA-1 gene linked to the human phosphoglycerate kinase (PGK) promoter. Expression of GATA-1 was demonstrated by super-shift analysis with a monoclonal antibody against murine GATA-1 using extracts of nonerythroid cytotoxic T-lymphocyte line (CTLL) cells transduced with the PGK-GATA-1 virus. Mouse bone marrow cells were transduced in vitro and transplanted into recipient animals. Polymerase chain reaction (PCR) analysis performed on DNA extracted from peripheral blood 12 to 40 weeks posttransplantation demonstrated the presence of the PGK-GATA-1 provirus. Proviral integrity and copy number were demonstrated by Southern blot analysis of DNA from spleen, thymus, and bone marrow tissues from the long-term animals. At 16 weeks posttransplant, animals that received cells transduced by the GATA-1 virus maintained a lower white blood cell (WBC) count and absolute neutrophil count (ANC) and a higher red blood cell (RBC) count than control animals that received cells transduced with a virus containing a neor gene. Erythropoiesis was stimulated in GATA-1 and control animals by phlebotomy. GATA-1 animals required more extensive phlebotomy to reach a hematocrit less than 25 and their hematocrit returned to normal levels sooner than control animals. The effect of twice-daily injections of 10 U recombinant erythropoietin (epo) was also examined. The hematocrit of GATA-1 animals showed a more rapid and elevated response to epo than the hematocrit of control animals. These data suggest that dysregulated expression of GATA-1 in primitive hematopoietic cells enlarges the pool of epo-responsive erythroid progenitor cells.
About 30% of patients with tumors (in relation to its extent) suffer from anemia which is usually asymptomatic. Etiologically this anemia may be characterized as secondary, so called anemia of chronic diseases. Disorders of iron metabolism, blood marrow insufficiency, extracorpuscular haemolysis, catabolism of patients with tumor burden and relative deficiency of erythropoietin all play a role in its pathogenesis. Anemia of cancer patients may be usually classified as normocytic and normochromic. Indication and timing for treatment of anemia of cancer is equivocal. Successful treatment of anemia seems to improve the quality of life of cancer patients. Indication depends, of course, on the severity of anemia, degree of adaptation and the presence of clinical symptoms related to anemia. Therapy with iron or anabolics is not very effective, therapy with recombinant erythropoietin is not available for all patients, especially for its high price. Transfusion therapy should be considered more carefully in relation with some data showing the possible negative influence of allogeneic blood derivatives on the progression of tumors, especially in patients immunodeficient after high dose chemotherapy and actinotherapy.
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