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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3126-3135.
Prepublished online as a Blood First Edition Paper on July 22, 2004; DOI 10.1182/blood-2003-07-2597.
 Previous Article | Next Article 
Submitted July 31, 2003
Accepted June 21, 2004
Gene expression profiling of normal and malignant CD34-derived megakaryocytic cells
Elena Tenedini, Maria Elena Fagioli, Nicola Vianelli, Pier Luigi Tazzari, Francesca Ricci, Enrico Tagliafico, Paolo Ricci, Luigi Gugliotta, Giovanni Martinelli, Sante Tura, Michele Baccarani, Sergio Ferrari, and Lucia Catani*
Servizio di Medicina Trasfusionale, Ospedale S. Orsola, Bologna, BO, Italy
Istituto di Ematologia e Oncologia Medica, Universita di Bologna, Bologna, BO, Italy
Unita Operativa Ematologia, Arcispedale 'S. Maria Nuova', Reggio Emilia, RE, Italy
Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, MO, Italy
* Corresponding author; email: lcatani{at}med.unibo.it.
Gene expression profiles of BM CD34-derived megakaryocytic cells (MKs) were compared in patients with essential thrombocythemia (ET) and healthy subjects utilizing oligonucleotide microarray analysis to identify differentially expressed genes and disease-specific transcripts. We found that pro-apoptotic genes such as BAX, BNIP3 and BNIP3L were downregulated in ET MKs together with genes that are component of the mitochondrial permeability transition pore complex, a system with a pivotal role in apoptosis. Conversely, anti-apoptotic genes like IGF1-R and CFLAR were upregulated in the malignant cells, as was the SDF1 gene, which favors cell-survival. Based on 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.
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