Leukemic cells and the cytokine patchwork.

Abstract

In leukemia, the clonal population is characterized by a hierarchical organization. Although the majority of the leukemic population is generated after post-determinic divisions, a subset of cells retain undifferentiated "blast" morphology. In addition, leukemic cells often have numerical or structural chromosomal abnormalities, aberrant gene expression patterns, and abnormal cell surface marker profiles. Despite these differences when compared to normal bone marrow and blood cells, leukemic cell survival and proliferation, just like that of normal progenitor cells, is influenced by hematopoietic growth factors. A major issue is whether differential regulation of normal and leukemic hematopoietic cells by cytokines can be exploited in antileukemic treatment or, in contrast, whether in vivo cytokine therapy may even be harmful to the patients. Here we review the results of recent experimental and clinical observations that investigated the influence of cytokines on leukemic cell growth and differentiation in vitro and in vivo. The majority of studies indicate that hematopoietic growth factors are involved in the regulation of proliferation and terminal differentiation of leukemic blast cells. Genetic aberrations involving cytokines or their receptors may contribute to leukemogenesis. Abundant interactions, cross-lineage stimulation, and aberrant response patterns seem to transform the complex cytokine network regulation of normal hematopoiesis into an even more interlaced "patchwork" that controls leukemic hematopoiesis. Since hematopoietic growth factors are present in high serum concentrations in patients with acute leukemia and myelodysplastic syndromes, consequences of possible interactions should be kept in mind even when well-defined human recombinant factors in single application are to be involved in antileukemic protocols.