Gene expression profiling of normal and malignant CD34-derived megakaryocytic cells.
Gene expression profiles of bone marrow (BM) CD34-derived megakaryocytic cells (MKs) were compared in patients with essential thrombocythemia (ET) and healthy subjects using oligonucleotide microarray analysis to identify differentially expressed genes and disease-specific transcripts. We found that proapoptotic genes such as BAX, BNIP3, and BNIP3L were down-regulated in ET MKs together with genes that are components of the mitochondrial permeability transition pore complex, a system with a pivotal role in apoptosis. Conversely, antiapoptotic genes such as IGF1-R and CFLAR were up-regulated in the malignant cells, as was the SDF1 gene, which favors cell survival. On the basis of the array results, we characterized apoptosis of normal and ET MKs by time-course evaluation of annexin-V and sub-G1 peak DNA stainings of immature and mature MKs after culture in serum-free medium with an optimal thrombopoietin concentration, and annexin-V-positive MKs only, with decreasing thrombopoietin concentrations. ET MKs were more resistant to apoptosis than their normal counterparts. We conclude that imbalance between proliferation and apoptosis seems to be an important step in malignant ET megakaryocytopoiesis.
Tenedini
Elena
E
Istituto di Ematologia e Oncologia Medica L. e A. Seràgnoli, Università di Bologna, Italy.
Fagioli
Maria Elena
ME
Vianelli
Nicola
N
Tazzari
Pier Luigi
PL
Ricci
Francesca
F
Tagliafico
Enrico
E
Ricci
Paolo
P
Gugliotta
Luigi
L
Martinelli
Giovanni
G
Tura
Sante
S
Baccarani
Michele
M
Ferrari
Sergio
S
Catani
Lucia
L
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D019070:Cell Lineage; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000503:physiopathology
D018952:Antigens, CD34