Abnormal Megakaryopoiesis in Patients With A JAK2 Exon 12 Mutation May Be A Non-Cell-Autonomous Phenomenon
1Diamantina Institute, University of Queensland, Brisbane, Queensland 4012, Australia
2School of Medicine, Faculty of Health Sciences, University of Queensland, Brisbane, Queensland 4012, Australia
3Translational Research Institute, University of Queensland, Brisbane, Queensland 4012, Australia
- *Corresponding Author:
- Linda M Scott
University of Queensland, Diamantina Institute
Translational Research Institute
37 Kent Street, Woolloongabba
Queensland 4012, Australia
E-mail: [email protected]
Received February 02, 2013; Accepted April 02, 2013; Published April 04, 2013
Citation: Scott LM (2013) Abnormal Megakaryopoiesis in Patients With A JAK2 Exon 12 Mutation May Be A Non-Cell-Autonomous Phenomenon. J Bone Marrow Res 1:116. doi:10.4172/2329-8820.1000116
Copyright: © 2013 Scott LM. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.