Differentially expressed genes in adult familial myelodysplastic syndromes.
The precise genetic events leading to myelodysplastic syndromes (MDSs) and leukemic transformation remain poorly defined. Even less is known about adult familial MDS. We report an adult MDS family in whom enriched tissue-specific transcripts were derived by subtractive hybridization of cDNA from the mononuclear and CD34+ cells of affected and unaffected family members. These expression libraries were then hybridized to Genome Discovery arrays containing 18 404 genes and expressed sequence tags, and several clusters of differentially expressed genes were identified. A group of 21 genes was underexpressed (>5-fold) in affected vs unaffected family members, and among these were transcription factors and genes involved in myeloid differentiation, such as ZNF140 and myeloid nuclear differentiation antigen (MNDA). Another group of 36 genes was overexpressed (>5-fold), and these encoded proteins belonging to signaling pathways, such as Ras- and Fos-related genes. The top two genes downregulated in this MDS family, ZNF140 and MNDA, were similarly altered in another MDS family, and in some cases of sporadic MDS. Our data suggest that we have identified genes differentially expressed in adult familial MDS, and that alteration of some of these genes may also be important for the evolution of different stages or severity of sporadic MDS.
Pradhan
A
A
Leukaemia Science Laboratories, Department of Haematological Medicine, The Rayne Institute, GKT School of Medicine, Denmark Hill, London, UK.
Mijovic
A
A
Mills
K
K
Cumber
P
P
Westwood
N
N
Mufti
G J
GJ
Rassool
F V
FV
D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013382:Subtraction Technique
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D012333:RNA, Messenger; D012334:RNA, Neoplasm