Hypoplastic anemia in B cell chronic lymphocytic leukemia: evolution of T cell-mediated suppression of erythropoiesis in early-stage and late-stage disease.
To define further the role of marrow T suppressor lymphocytes in the pathogenesis of the hypoproliferative anemia in all Rai clinical stages of B cell chronic lymphocytic leukemia (CLL), marrow erythroid progenitor cell (CFU-E and BFU-E) frequency, marrow T gamma lymphocyte frequency per 1,000 nucleated marrow cells, and T cell-erythroid progenitor cell interactions were examined in 30 CLL patients and normal control subjects. As compared with control subjects, decreased numbers of CFU-E and BFU-E were found in patient marrow depleted of neoplastic B cells in all Rai stages of the disease. As a group, Rai stage III through IV patients with or without aplasia (CLL-aplasia) had significantly fewer CFU-E and BFU-E than did Rai O through II stage patients. The numbers of T gamma cells infiltrating CLL marrows were increased 3, 9, and 20 times normal in Rai O through II, Rai III through IV, and CLL-aplasia groups, respectively. Removal of T cells from marrow increased growth of CFU-E and BFU-E in all Rai O through IV patients, but the increase was significant in the CLL-aplasia group only (P less than .05). However, autologous coculture of marrow T cells or T gamma cells but not B cells with marrow B + T-depleted null cells at ratios of 0.2:1 to 1:1 suppressed CFU-E and BFU-E growth in all three patient groups. We conclude that the hypoproliferative anemia occurring in the course of B cell CLL is due to gradual accumulation in the marrow of T gamma lymphocytes which suppress erythroid progenitor cell growth. T gamma cell suppression of erythropoiesis and marrow T gamma cell expansion is detectable in the earliest Rai stages of the disease.
Mangan
K F
KF
D'Alessandro
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L
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000209:etiology / Q000473:pathology*; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D001853:Bone Marrow / Q000473:pathology; D002469:Cell Separation; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000097:blood / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology* / Q000502:physiology; D013997:Time Factors
D000911:Antibodies, Monoclonal