[Anagrelide-induced changes of megakaryopoiesis during therapy of XXXX with @entity1148 ].

@entity1 @entity1148 @entity1364 @entity882 @entity102 @entity4018 @entity1428
@entity1148 in the course of @entity102 like @entity4018 ( @entity4018 ) and of course essential @entity1148 (ET), are characterized by life-threatening complications. In a number of clinical trials the recently introduced drug Agrylin((R)) has proven to be very effective. The normalization of the platelet count was related to an interference with megakaryocyte maturation leading to a left-shifting of this cell lineage and/or a reduced proliferation. However, until now no systematic study has been performed on the relationship between development of megakaryopoiesis and proliferative activity. In this investigation we included 10 @entity1 with @entity4018 and 5 @entity1 with ET that had received Agrylin((R)) for a period ranging between 6 and 70 months. Following therapy this cohort revealed a decrease in the platelet count from 1,104x10(9)/l at diagnosis to 485x10(9)/l. In this context we focused on an immunohistochemical and morphometric analysis of the @entity1428 (+) megakaryopoiesis involving also endomitotic reduplication, by applying a double-immune incubation technique with the @entity1364 ( @entity1364 ). Moreover, we determined the changes of fiber density during observation time. According to our results, the @entity882 effect of Agrylin((R)) is based on an arrest in the dynamics of megakaryocyte maturation towards large (mature) platelet-shedding (polyploid) cells. This pathomechanism causes a significant increase in the number of promegakaryoblasts and megakaryoblasts. On the other hand, the total amount of @entity1428 (+) megakaryocytic cells is not increased. Related to the peculiar cell biology of endomitotic reduplication during the maturation process and its different periods alloted to each single step, @entity1364 activity (late G1- and S-phase of the cell cycle) is found to be enhanced in the megakaryocyte precursors. Finally, no significant influence of Agrylin((R)) on the evolution of @entity4018 is detectable and there is a general improvement of hematological data especially in @entity4018 .
