Table 1.
In vitro growth rates of cells harboring resistance mutations [8].
Table 2.
In vivo growth rates of cells harboring resistance mutations.
Figure 1.
Existence and composition of pre-existing resistance.
(a) The panel shows the distribution of the number of distinct resistant clones at the time of diagnosis. There are (blue),
(green), or
(red) leukemic stem cells present at the time of diagnosis. The per base pair mutation rate is
. (b) The panel displays the expected number of resistant cell types as a function of the detection size,
, for varying mutation rates. (c) The expected number of resistant types at diagnosis is shown as a function of the mutation rate
, for varying numbers of leukemic stem cells at diagnosis,
. (d) The expected number of resistant cell types is displayed as a function of time
in years, for varying mutation rates
.
Figure 2.
The frequency of pre-existing resistant cells.
(a) The panel displays the expected number of resistant cells of each type at diagnosis for leukemic stem cells. (b) The expected number of resistant cells of each type at diagnosis for
leukemic stem cells is shown. (c) The panel displays the time evolution of the average number of cells of each type. (d) The ratio of the expected number of cells of each type to the expected total resistant cell number as a function of time. The mutation rate is
per base per cell division for all panels.
Figure 3.
The frequency of T315I and F317L mutations at diagnosis.
The figure shows the distribution of the number of T315I-positive (a) and F317L-positive (b) cells in the population at detection time. Parameters are and
, and simulations are run for 100,000 samples.
Figure 4.
(a) The panel displays the probability that there exists at least one cell with any specified mutation in the CML stem cell population at detection time. Parameters are and
. (b) The probability that the leukemic stem cell population is free of mutants conferring resistance to imatinib, dasatinib, imatinib plus dasatinib, and all three drugs at detection time. Parameters are
(red),
(blue), and
.