 | Figure 1
Nature Medicine
- 12, 1181 - 1184 (2006)
Published online: 1 October 2006; | doi:10.1038/nm1487
Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implicationsIngo Roeder, Matthias Horn, Ingmar Glauche, Andreas Hochhaus, Martin C Mueller & Markus Loeffler | | | | Figure 1. BCR-ABL1 transcript dynamics.
(a) CML under imatinib treatment. Data points represent median and interquartile range of BCR-ABL1 transcript levels in peripheral blood, determined in two independent study populations: BCR-ABL1/BCR percentages in 68 individuals with imatinib-treated CML, previously published12 (red) and BCR-ABL1/ABL1 percentages in 69 individuals with imatinib-treated CML from the German cohort of the IRIS trial (blue). Solid lines represent corresponding simulation results of BCR-ABL1 levels starting from a model system that had developed a CML with more than 99% BCR-ABL1–positive cells; applied degradation intensities r
deg = 0.033 (red line) and r
deg = 0.028 (blue line). 'Intensity' is a parameter that describes the probability of an individual cell being affected within a time step of 1 h. (b) Heterogeneity of responses. Selection of six qualitatively different BCR-ABL1 dynamics in individuals (three from the previously published study12 (red) and three from the German IRIS cohort (blue)). Corresponding simulations (color-matching solid lines) were obtained by quantitative variation of the imatinib-induced degradation (r
deg) and proliferation inhibition (r
inh) intensities: r
inh = 0.05, r
deg = 0.033 (dark blue); r
inh = 0.005, r
deg = 0.012 (medium blue); r
inh = 0.005, r
deg = 0.028 (light blue); r
inh = 0.05, r
deg = 0.0375 (dark red); r
inh = 0.05, r
deg = 0.028 (medium red); r
inh = 0.005, r
deg = 0.0375 (light red). (c) CML relapse upon treatment cessation. Simulated BCR-ABL1/BCR percentage after treatment cessation, starting from the indicated average simulation of imatinib treatment. Data points represent individual measurements in three different people, taken from the previously published study12. In contrast to the simulation (solid line), these individuals had different BCR-ABL1/BCR percentages (ranging from 0.01% to 5%) at or shortly before treatment cessation. Model details and parameters are given in the Supplementary Note and Supplementary Tables 1 and 2.
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