Medline ® Abstracts for References 80,81

Peripheral blood and bone marrow mononuclear cells from patients with refractory anemia (RA) or RA with sideroblasts (defined according to the revised French-American-British classification with less than 5% blast cells in the bone marrow) were analyzed using a panel of monoclonal antibodies directed against leukocyte antigens on B lymphocytes, T lymphocytes, monocytes, and myeloid cells. In the peripheral blood an increased proportion of T lymphocytes (and correspondingly a decreased proportion of B cells) could be demonstrated. However, when expressed in terms of absolute numbers, the T cell component was depressed because of severely decreased numbers of T4+ helper cells. In contrast, the absolute numbers of T8+ suppressor cells were either normal or increased in the majority of the patients. This resulted in markedly decreased ratios of T4+/T8+ cells, which were closely correlated to the number of transfusions given to the patients because of their refractory anemia. Finally, nearly all of the patients exhibited decreased numbers of cells reactive with the N901 natural killer (NK) antibody, thus explaining our earlier finding of decreased NK activity in these patients. In the bone marrow increased proportions of myeloid cells reactive with monoclonal antibodies present on immature myeloid cells (My7 and My9) were found, suggesting the presence of malignant clones. Indeed, when the numbers of My7+ cells and the morphologic evaluations of bone marrow smears at the time of diagnosis were compared to the progression of the disease, a group of patients with high numbers of My7+ cells and normal morphology could be identified that had a high probability of progression to refractory anemia with an excess of blasts or to overt acute myeloid leukemia. Thus, the use of antibodies defining leukocyte differentiation antigens might be of significant value in the diagnosis and prognostication of the myelodysplastic syndromes. These findings are discussed in relation to the pathogenesis of this potentially premalignant condition with special emphasis on possible defects in the immunologic defense mechanisms against early neoplasias.

The myelodysplastic syndromes (MDS) are disorders in which the abnormalities are thought to be confined to cells of the myeloid series. However, examination of peripheral blood from 56 patients with MDS showed that the majority had low lymphocyte counts. In a detailed study of 25 patients, using OKT3, OKT4 and OKT8 monoclonal antisera together with SRBC rosettes, it was shown that there is a consistent and significant reduction in peripheral blood T lymphocytes. This decrease was primarily confined to the OKT4-defined helper subpopulation. There is a consequent relative increase in the OKT8-defined subset but in absolute numbers however, suppressor cells are reduced compared to normal particularly in those patients with lymphopenia. No correlations between T cell abnormalities and the different morphological groups of MDS were found. The possible implications of the reversed helper/suppressor ratio in the pathogenesis of MDS are discussed.