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.