Haema 2011; 2(2): 205-213
by Αrgiris S. Symeonidis
Associate Professor Hematology University of Patras, Greece
Del-5q syndrome comprises a distinct disease entity in the area of MDS, not only due to its characteristic clinical and hematological manifestations, but also due to its typical gene expression profile, which guides a specific pathogenesis. After the delineation and refinement of the Commonly Deleted Region – CDR, many genes, with a possible pathogenetic role in this syndrome were recognized. Del-5q syndrome is the result of gene haploinsufficiency, of whom the most important are EGR1, which codes for a T-lymphocyte transcription factor, IRF1, an interferon regulatory gene, SPARC, which codes for an important matrix glycoprotein, CDC25 and PP2A, two regulatory cell cycle proteins, miR-145 and miR-146a, which have both been implicated in the deranged megakaryocytopoiesis and thrombocytosis of the syndrome, and finally RPS14, which contributes to association of the 40S and 60S ribosomal subunit. RPS14 haploinsufficiency is the major pathogenetic mechanism of ineffective erythropoiesis and apoptosis of the immature erythropoietic cells, which are dominant features in this syndrome. The risk of leukemic transformation is relatively low, and has been calculated as high as 15% at 5 years. Therapeutic intervention in this disease has changed dramatically the last few years, after the recognition of the high efficacy of lenalidomide, as treatment of symptomatic patients. Lenalidomide induces hematologic and cytogenetic responses in 60-85% of the treated patients, which may last for several years. It has been argued whether this drug may enhance clonal evolution and leukemic transformation, and more clinical experience is clearly needed to answer this question. However, when a favorable response is lost, it is very difficult to be again resumed, and these patients should be managed with more aggressive approaches, when their clinical condition allows such kind of treatment.