Relationship of differential gene expression profiles in CD34+ myelodysplastic syndrome marrow cells to disease subtype and progression.
Microarray analysis with 40 000 cDNA gene chip arrays determined differential gene expression profiles (GEPs) in CD34(+) marrow cells from myelodysplastic syndrome (MDS) patients compared with healthy persons. Using focused bioinformatics analyses, we found 1175 genes significantly differentially expressed by MDS versus normal, requiring a minimum of 39 genes to separately classify these patients. Major GEP differences were demonstrated between healthy and MDS patients and between several MDS subgroups: (1) those whose disease remained stable and those who subsequently transformed (tMDS) to acute myeloid leukemia; (2) between del(5q) and other MDS patients. A 6-gene "poor risk" signature was defined, which was associated with acute myeloid leukemia transformation and provided additive prognostic information for International Prognostic Scoring System Intermediate-1 patients. Overexpression of genes generating ribosomal proteins and for other signaling pathways was demonstrated in the tMDS patients. Comparison of del(5q) with the remaining MDS patients showed 1924 differentially expressed genes, with underexpression of 1014 genes, 11 of which were within the 5q31-32 commonly deleted region. These data demonstrated (1) GEPs distinguishing MDS patients from healthy and between those with differing clinical outcomes (tMDS vs those whose disease remained stable) and cytogenetics [eg, del(5q)]; and (2) molecular criteria refining prognostic categorization and associated biologic processes in MDS.
Sridhar
Kunju
K
Hematology Division,Stanford University Medical Center, 875 Blake Wilbur Drive, Stanford, CA 94305, USA.
Ross
Douglas T
DT
Tibshirani
Robert
R
Butte
Atul J
AJ
Greenberg
Peter L
PL
D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000378:metabolism; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000648:ultrastructure; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000235:genetics; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D015398:Signal Transduction / Q000235:genetics
D018952:Antigens, CD34; D018076:DNA, Complementary