A critical review of the molecular pathophysiology of lenalidomide sensitivity in 5q − myelodysplastic syndromes

Abstract

The 5q deletion is a chromosomal abnormality that is observed in a subset of myelodysplastic syndromes (MDS). When isolated, this abnormality defines a specific clinical syndrome termed MDS associated with isolated deletion 5q, presenting with macrocytic anemia, normal platelet count or slight thrombocytosis, hypolobated megakaryocytes and fewer than 5% blasts in the bone marrow. MDS with the 5q deletion have a particular sensitivity to treatment with lenalidomide, a thalidomide analog. In this article, molecular changes in 5q− MDS derived from haploinsufficiency of genes encoded from the deleted region in 5q are reviewed, and mechanisms that link these molecular lesions with lenalidomide sensitivity are proposed.

Keywords::

• Myelodysplastic syndromes
• lenalidomide
• 5q− syndrome
• haploinsufficiency
• NF-κB
• cell adhesion

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