@article{Brady L. Stein_Donna M. Williams_Nae-Yuh Wang_Ophelia Rogers_Mary Ann Isaacs_Naveen Pemmaraju_Jerry L. Spivak_Alison R. Moliterno_2010, place={Pavia, Italy}, title={Sex differences in the JAK2V617F allele burden in chronic myeloproliferative disorders}, volume={95}, url={https://haematologica.org/article/view/5650}, DOI={10.3324/haematol.2009.014407}, abstractNote={<strong>Background</strong> The <em>JAK2</em><sup>V617F</sup> allele burden is a variable measure, determined by the frequency of mitotic recombination events and the expansion of <em>JAK2</em><sup>V617F</sup> clones. Since variability in the <em>JAK2</em><sup>V617F</sup> allele burden is partly responsible for the distinct phenotypes seen in the myeloproliferative disorders, the objective of this study was to identify modifiers of the allele burden.<strong>Design and Methods</strong> Blood samples were obtained between May 2005 and January 2009 from 272 patients with essential thrombocytosis, polycythemia vera, and myelofibrosis. The <em>JAK2</em><sup>V617F</sup> allele burden was measured by an allele-specific quantitative polymerase chain reaction using DNA from purified neutrophils. Repeated measures, on average 2 years apart, were available for 104 patients.<strong>Results</strong> Sex, age at diagnosis, and disease duration all independently influenced the <em>JAK2</em><sup>V617F</sup> allele burden. When considering all patients with myeloproliferative disorders, women had significantly lower allele burdens than men (<em>P</em>=0.04). In those patients with repeated measures, the increase in allele burden per year between the first and second evaluations was significantly less in females than in males. Among those who experienced disease evolution, females were 4.5 times more likely to have evolution from essential thrombocytosis to polycythemia vera, but 0.23 times as likely to have evolution from essential thrombocytosis to myelofibrosis.<strong>Conclusions</strong> Sex is an independent factor accounting for variability in the <em>JAK2</em><sup>V617F</sup> allele burden. We speculate that lower allele burdens in females reflect a lower frequency of mitotic recombination events in females than in males, and should be considered when evaluating the relationship of allele burden to disease phenotype and also in evaluating responses to <em>JAK2</em><sup>V617F</sup>-inhibitors. Because sex may influence genotype and/or clonal expansion, underpinning the variability in <em>JAK2</em><sup>V617F</sup&gt; allele burden, it will be important to explore factors that determine susceptibility to mitotic recombination events.}, number={7}, journal={Haematologica}, author={Brady L. Stein and Donna M. Williams and Nae-Yuh Wang and Ophelia Rogers and Mary Ann Isaacs and Naveen Pemmaraju and Jerry L. Spivak and Alison R. Moliterno}, year={2010}, month={Jun.}, pages={1090-1097} }