In vitro hematopoiesis in myelodysplasia: liquid and soft-gel culture studies

Abstract

In vitro clonogenic assays of bone marrow have provided invaluable information about the complex regulatory mechanisms controlling hematopoiesis, both normal and abnormal, and have led to the discovery of colony stimulating factors. Our understanding of the abnormalities of growth and differentiation characterizing the MDS have been advanced largely through use of these assays. Abnormalities commonly seen in cultures of marrow from patients with MDS include decreased or absent colony growth, abortive cluster formation, and defective maturation of cells within the colonies. Although some investigators have defined growth patterns as "leukemic" and "nonleukemic" and have tried to correlate growth patterns with potential for evolution to acute leukemia, these methods are difficult to apply to any given case. Given the wide variety of techniques used to collect cells and the lack of standard sources for stimulating growth factors, the results, not surprisingly, have been inconclusive in predicting both prognosis and progression to acute leukemia. New methods by which clonogenic assays can be standardized, such as purification of the clonogenic cells and use of recombinant growth factors, should allow these assays to advance our understanding of MDS, develop new therapies, and predict responses to therapy in individual patients.