Figure 5.
The ASXL1G643W variant is associated with increased resistance to chemotherapy. (A) Schematic outline of the chemotherapy treatment set-up. Briefly, sublethally irradiated recipient mice were transplanted with bone marrow (BM) cells harvested from leukemic mice. Twenty-one days after transplant, recipient mice were treated with standard induction chemotherapy for 5 days. Three days later, blood was harvested for analysis and leukemic mice were subsequently monitored for disease development. (B) Analysis of peripheral leukemic numbers in mice after chemotherapy/vehicle treatment. Each data point represents the fold change difference between the vehicle-treated and chemotherapy-treated groups for a given clone (n=12 mice per clone). The two different genotypes, Asxl1+/+; CebpaΔ/p30 and Asxl1G643W/G643W CebpaΔ/p30, were represented by four and three clones, respectively. The responses of individual clones are indicated in the Online Supplementary Figure S4. A one-tailed Mann-Whitney U test was used to assess statistical significance. (C) Kaplan-Meyer survival curves of leukemic mice after chemotherapy/vehicle treatment. The data represent the aggregate of two different leukemic clones (n=6 recipients of each clone, clones 1-2 and 5-6) for each of the two different genotypes (Asxl1+/+; CebpaΔ/p30 and Asxl1G643W/G643W; CebpaΔ/p30).