Fig. 5: The MEK-inhibitor trametinib prolongs survival of CMML#1-MN1 mice when combined with azacitidine. | Leukemia

Fig. 5: The MEK-inhibitor trametinib prolongs survival of CMML#1-MN1 mice when combined with azacitidine.

From: Effective drug treatment identified by in vivo screening in a transplantable patient-derived xenograft model of chronic myelomonocytic leukemia

Fig. 5

a Schematic representation of the treatment regimens (Aza, azacitidine; Tram, trametinib). b Monitoring of CMML burden in recipient mice at week 15 after transplantation (each dot represents one mouse; mean ± SEM). c Survival of NSGS recipient mice engrafted with CMML#1-MN1 cells and treated with vehicle (n = 10), trametinib (n = 8), azacitidine (n = 10) and the combination of trametinib+azacitidine (n = 7). d Spleen weight of NSGS recipient mice engrafted with CMML#1-MN1 cells and treated with vehicle, trametinib, azacitidine and the combination of trametinib+azacitidine at sacrifice (each dot represents one mouse; mean ± SEM). e White blood cell count in peripheral blood of CMML#1-MN1 bearing mice treated with vehicle, trametinib, azacitidine and the combination of trametinib+azacitidine 4 weeks after treatment start and at sacrifice (number of individual mice is indicated in the figure; mean ± SEM). f Hemoglobin levels in peripheral blood of CMML#1-MN1 bearing mice treated with vehicle, trametinib, azacitidine and the combination of trametinib+azacitidine 4 weeks after treatment start and at sacrifice (number of individual mice is indicated in the figure; mean ± SEM). g Platelet count in peripheral blood of CMML#1-MN1 bearing mice treated with vehicle, trametinib, azacitidine and the combination of trametinib+azacitidine 4 weeks after treatment start and at sacrifice (number of individual mice is indicated in the figure; mean ± SEM). h Effect of the combination treatment in five different CMML patients (unrelated to the CMML#1-MN1 cells). Primary CMML cells were treated with vehicle, azacitidine (500 nM), trametinib (20 nM) or the combination of azacitidine (500 nM) + trametinib (20 nM) and plated in duplicate in CFC media. After 20 days colonies were counted and expressed as percentage of the vehicle-treated cells. White dots within all groups represent cells from a patient without mutation in a signaling gene (n = 5, mean ± SEM). i Immunoblotting for p-ERK and ERK in azacitidine/trametinib- and vehicle-treated CMML patients (n = 3) and CMML#1-MN1 (n = 1) cells from third recipient mice at 6 h after treatment. j Average p-ERK-to-ERK ratio from immunoblots shown in Fig. 5i as percentage of vehicle-treated CMML cells (n = 4, mean ± SEM).

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