Journal de la recherche osseuse
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Abnormal Megakaryopoiesis in Patients With A JAK2 Exon 12 Mutation May Be A Non-Cell-Autonomous Phenomenon

Linda M Scott

Background: In contrast to patients with JAK2V617F-positive polycythemia vera, those patients with a JAK2 exon 12 mutation present with platelet counts within the normal range. Furthermore, the bone marrow samples from most JAK2 exon 12 mutation-positive patients lack the prominent clusters of large, bizarre-looking megakaryocytes that characterize classic JAK2V617F-positive polycythemia vera. This study examines the effects on megakaryopoiesis associated with the presence of a JAK2 exon 12 mutation.

Results: These mutations were found to be present within the platelet population of affected individuals at levels comparable to those in paired granulocyte samples, suggesting that they do not profoundly affect the viability of platelets or their precursors. Furthermore, in vitro assays demonstrate that JAK2K539L is capable of interacting with and mediating intracellular signalling through the thrombopoietin receptor. An interesting phenomenon was identified when the genotype of individual atypical megakaryocytes present in the bone marrow was determined: only a proportion of those that may be observed in JAK2 exon 12 mutation-positive patients were positive for this mutation.

Conclusions: It remains unclear why patients positive for a JAK2 exon 12 mutation do not have the elevated platelet counts typically observed in patients with classic JAK2V617F-positive PV. The analysis of megakaryocytes with atypical nuclear structure suggests that other hematopoietic or non-hematopoietic cells within the bone marrow environment of MPN patients may influence the phenotype of cells that themselves lack a JAK2 mutation.