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The role of cereblon in lenalidomide therapy of del(5q) myelodysplastic syndrome
Bokorová, Radka ; Fuchs, Ota (advisor) ; Lukačková, Renata (referee) ; Krijt, Jan (referee)
Myelodysplastic syndrome (MDS) with deletion of the long arm of the chromosome 5 (5q - syndrome, del( 5q)) can be characterized by anemia, macrocytosis, a normal or high platelet count, and hypolobulated megakaryocytes in the bone marrow. 5q - syndrome belongs to low - risk MDS, which means low risk to transform to acute myeloid leukemia. 5q - syndrome is ass ociated with female predominance and older age. Another sign is transfusion burden that is treated by erythropoiesis - stimulating agents (ESA) as erythropoietin (EPO). Moreover, the response of MDS patients is around 30 - 60% with the median of the response b eing ~ 24 months. The second line of treatment is lenalidomide (LEN) which is a derivate of teratogenic analog thalidomide. LEN increases erythropoiesis and inhibits the growth of del(5q) erythroid progenitors in vivo and it does not have a significant effe ct on the growth of normal CD34+ progenitors or cytogenetically normal progenitors in MDS with del(5q) clones. LEN is used as therapy in multiple myeloma, myelodysplastic syndrome, and lymphoma. LEN is an expensive agent and not every MDS patient re sponds to this therapy. This is a reason why is a need to find a biomarker for the determination of successful treatment. Some multiple myeloma studies showed that cereblon can be the biomarker...
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