Prokopenko I. Peculiarities of megakaryocytopoesis in myelofibrosis with myeloid metaplasia patients exposed to ionizing radiation following the Chernobyl accident

Dissertation is devoted to study of the megakaryocytopoiesis in myelofibrosis with myeloid metaplasia (MMM,) patients, exposed to ionizing radiation (IR) in doses 0.21 - 49.0 cSv due to Chernobyl accident. The current pathogenetic hypothesis in MMM is that clonal proliferation of megakaryocytes is accompanied by an abnormal cytokine release. Features of MMM that developed after exposure to IR has not been studied before. Using morphometry, cytomorphological, cytochemical methods and functional tests (aggregation of platelets) some peculiarities of megakaryopoiesis in IR-exposed MMM patients were revealed in comparison with non-exposed patients and prognostic criteria for IR-exposed MMM patients were proposed. For IR-exposed MMM patients there were typical more severe osteoproliferative changes and higher concentration of platelet-derived growth factor BB (PDGF-BB) in bone marrow at initial stages of disease; more profound and longer hyperplasia of megakaryocytopoiesis, correlation between PDGF-BB concentration and absolute number of megakaryocytes with predominance of hypolobular cells; activation and acceleration of cell cycle (according to the ratio of basophilic and polychromatophilic to apoptotic megakaryocytes), higher activity of acid phosphatase in megakaryosytes, and better aggregation of platelets under induction with collagen, adrenaline and adenophosphate. New data of interrelation between individual doses of IR (ID) and megakaryopoiesis were found: positive correlation of ID and absolute count of all megakaryocytes and megakaryocytes with hypolobular nuclei (ID>1.58 cSv), negative correlation between ID and functional activity of megakaryocytes (ID>8.92 cSv), ID and absolute megakaryocytes count (ID>9.67 cSv), ID and megakaryocytic acid phosphatase activity (ID>11.69 cSv). Different influence of IR on megakaryocytopoiesis (stimulation under ID>1.58 cSv and inhibition under ID>9.67 cSv) were established. Obtained results can be used for the improving of diagnostics of IR-exposed MMM patients, development of modern prognostics models and optimization of treatment strategy for IR-associated MMM