Abnormal megakaryopoiesis in patients with a JAK2 exon 12 mutation may be a non-cell-autonomous phenomenon

Scott, Linda M. (2013) Abnormal megakaryopoiesis in patients with a JAK2 exon 12 mutation may be a non-cell-autonomous phenomenon. Journal of Bone Marrow Research, 1 2: 1000116.1-1000116.5. doi:10.4172/2329-8820.1000116

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Author Scott, Linda M.
Title Abnormal megakaryopoiesis in patients with a JAK2 exon 12 mutation may be a non-cell-autonomous phenomenon
Journal name Journal of Bone Marrow Research   Check publisher's open access policy
ISSN 2329-8820
Publication date 2013-04-04
Sub-type Article (original research)
DOI 10.4172/2329-8820.1000116
Open Access Status DOI
Volume 1
Issue 2
Start page 1000116.1
End page 1000116.5
Total pages 5
Place of publication Los Angeles, CA, United States
Publisher OMICS Publishing Group
Collection year 2014
Language eng
Formatted abstract
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.
Keyword JAK2 exon 12 mutation
Bone marrow microenvironment
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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Created: Fri, 13 Sep 2013, 11:52:31 EST by Linda Scott on behalf of UQ Diamantina Institute