Going from genes to proteins in myelodysplastic syndromes
- Department of Hematology, Hemostasis, and Oncology, Hannover Medical School, D-30625 Hannover, Germany
The myelodysplastic syndromes (MDS) are a heterogeneous group of malignant clonal diseases of bone marrow stem and progenitor cells ranging clinically from mild asymptomatic anemia or other cytopenias to rapid transformation to acute leukemia. The early stages of MDS are characterized by dysplasia and increased apoptosis of bone marrow cells resulting in the characteristic pattern of bone marrow hypercellularity with peripheral blood cytopenias (1, 2). Immune mechanisms driven by autoreactive T cell clones and associated cytokines have been implicated in the pathogenesis of ineffective hematopoiesis in early MDS (3), and the degree of anemia correlates well with the serum concentration of TNF-α (4). During disease progression, increasingly complex genetic alterations within the marrow cells lead to profound differentiation defects with accumulation of blast cells in the marrow and ultimately development of frank acute leukemia in 30–40% of patients. MDS can therefore be regarded as a preleukemic disease state, which can be monitored to elucidate the successive genetic and cellular events important for leukemogenesis.
What is the value of the paper by Aivado et al. (5), published in this issue of PNAS, for our understanding of MDS? By generating serum proteome profiles in a large group of MDS patients and controls, Aivado et al. for the first time demonstrate that concentrations of the chemokines CXCL4 and CXCL7, but not other peptides, are selectively decreased in serum from MDS patients. Although this decrease was more pronounced in patients with advanced disease stage, it was also detectable in early stages of MDS. These observations were corroborated by CXCL4-specific immunoassays on both platelet-free plasma and platelets from MDS and non-MDS cytopenia patients. Deficiency of both CXCL4 and CXCL7 may be one of several causes for the increased rate of infections in MDS patients. Additional causes include decreased neutrophil numbers and absence of secondary …
*To whom correspondence should be addressed. E-mail: ganser.arnold{at}mh-hannover.de
