Increased megakaryopoiesis and thrombopoiesis induced by plasma from myelofibrosis (MF) and essential thrombocythemia (ET) patients.

YAÑUK DB; MARTA RF; CELLUCCI AS; DE LUCA G; DISCIANNI LUPI AD; HELLER PG; GOETTE NP; LEV PR

Congreso; Congress of the International Society on Thrombosis and Haemostasis (ISTH); 2023

Background: Myelofibrosis (MF) and Essential Thrombocythemia (ET) are characterized by abnormal proliferation of hematopoietic progenitors and chronic inflammation. MF presents bone marrow fibrosis, which confers a worse prognosis.Aims: Our objective was to evaluate the effect of plasma from MF and ET patients on megakaryo/thrombopoiesis.Methods: Megakaryopoiesis was evaluated in cord blood-derived CD34+ progenitors cultured with TPO and 10% recalcified plasma (patients n=51, 29 MF and 22 ET; controls n=45) for 12 days. Megakaryocytes (MKs) number and percentage of CD61 (differentiation) and CD42b (maturation) cells were quantified by optical microscopic and by flow cytometry. Thrombopoiesis was evaluated in mature MKs cultured for 72 hours with TPO and 10% recalcified plasma. Proplatelets (PP) were counted using an inverted microscope and PP morphology was analyzed by immunofluorescence. Statistical analysis was performed using Mann Whitney and Spearman´s correlation tests.Results: An increase in MKs number and maturation was observed in the presence of plasma from MF compared to ET and controls (p < 0.001, p< 0.0001, respectively). CD61 and CD42b percentages were higher in both pathologies compared to controls (MF: p< 0.0001, ET: p< 0.05). The increase in total and mature MKs was also observed in MF JAK2V617F patients compared to CALR-positive (p < 0.05) and in high-risk group according MIPSS.70 score (p=0.06, p< 0.05, respectively). In contrast, PP count was increased in ET (p < 0.001) while PP morphology was normal. A direct correlation was observed between PP count and peripheral platelet count in both pathologies (p < 0.05).Conclusion(s): Exacerbated proliferation, differentiation and MKs maturation induced by MF patient plasma suggests an increase in soluble mediators that could be related to the chronic inflammatory state present in this disorder. In contrast, increased PP formation was exclusively observed in ET, in accordance with elevated peripheral platelet count. These results suggest a differential profile of soluble inflammatory mediators between MF and ET.