Clinical implications of gene expression profiling in myelodysplastic syndromes: recognition of ribosomal and translational gene dysregulation and development of predictive assays.
Myelodysplastic syndromes (MDS) are a group of haematopoietic stem cell disorders that pose a unique challenge for gene expression profiling by virtue of their inherent heterogeneity. Despite monoclonality of MDS, the marrow picture is complicated by the presence of not only stromal cells but also by varying stages of differentiating diseased cells belonging to all three lineages. Now that reproducible results can be obtained from nanograms of RNA, it is possible to derive useful information from even a limited number of cells; for example, dysregulation of ribosomal and translational genes was detected in MDS patients compared to controls using a small number of CD34+ cells. Gene expression profiling in MDS patients treated with lenalidomide or 5-azacitidine+thalidomide yielded signatures which differentiated responders from non-responders. These biologic and clinical insights are providing the framework on which to build a new model of these diseases which, despite their heterogeneity, manifest certain unifying themes.
Galili
Naomi
N
St. Vincent's Comprehensive Cancer Center, 325 West 15th Street, New York, NY 10011, USA. ngalili@aptiumoncology.com
Raza
Azra
A
D018952:Antigens, CD34 / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D049109:Cell Proliferation; D000077209:Decitabine; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D000077269:Lenalidomide; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics; D012270:Ribosomes / Q000235:genetics*; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use
D018952:Antigens, CD34; D013792:Thalidomide; D000077209:Decitabine; D000077269:Lenalidomide; D001374:Azacitidine