Figure 2.
Figure 2. Comparison of XCIPs with proportion of V617F+ granulocytes. (A) Median and 95% confidence intervals produced by Monte Carlo simulations of estimated clonal granulocytes for a given proportion of V617F+ cells. Two estimates for the variability of granulocytes around T-cell proportion were used, based on published age-specific data in healthy women.29 The dashed line shows the “true” line under the null hypothesis that V617F is the initiating mutation, that is, that the proportion of clonal granulocytes is the same as the proportion of V617F+ cells. The individual point estimates from the 20 women studied (Figure 1C) are shown. (B) Worked examples demonstrating the effects of assuming equal T-cell and granulocyte X-inactivation patterns on the estimated proportion of clonal granulocytes from (i) a patient in whom 50% of T cells and granulocytes carry active Xm and (ii) a patient in whom 50% of T cells and 75% of granulocytes carry active Xm. The estimated proportion of clonally derived granulocytes from XCIP analysis was derived from (ii) using the standard formula21,24 as follows: with similar calculations for (i). Note that if the V617F mutation occurs in an Xm cell, the unequal XCIPs in T cells and granulocytes result in an apparent excess of clonally derived cells. GC indicates proportion of clonally derived granulocytes; Xm, cell with active maternal X chromosome; Gr, granulocytes; T, T cells. \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\ G_{C}=\frac{R_{G}-R_{T}}{R_{G}+1}=\frac{80{/}20-50{/}50}{1+80{/}20}=60\%,\ \] \end{document}
Comparison of XCIPs with proportion of V617F+ granulocytes. (A) Median and 95% confidence intervals produced by Monte Carlo simulations of estimated clonal granulocytes for a given proportion of V617F+ cells. Two estimates for the variability of granulocytes around T-cell proportion were used, based on published age-specific data in healthy women.29  The dashed line shows the “true” line under the null hypothesis that V617F is the initiating mutation, that is, that the proportion of clonal granulocytes is the same as the proportion of V617F+ cells. The individual point estimates from the 20 women studied (Figure 1C) are shown. (B) Worked examples demonstrating the effects of assuming equal T-cell and granulocyte X-inactivation patterns on the estimated proportion of clonal granulocytes from (i) a patient in whom 50% of T cells and granulocytes carry active Xm and (ii) a patient in whom 50% of T cells and 75% of granulocytes carry active Xm. The estimated proportion of clonally derived granulocytes from XCIP analysis was derived from (ii) using the standard formula21,24  as follows: with similar calculations for (i). Note that if the V617F mutation occurs in an Xm cell, the unequal XCIPs in T cells and granulocytes result in an apparent excess of clonally derived cells. GC indicates proportion of clonally derived granulocytes; Xm, cell with active maternal X chromosome; Gr, granulocytes; T, T cells.
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