Fig. 6: Alternating THU + Dec with THU + 5Aza week to week. | Leukemia

Fig. 6: Alternating THU + Dec with THU + 5Aza week to week.

From: Decitabine- and 5-azacytidine resistance emerges from adaptive responses of the pyrimidine metabolism network

Fig. 6

NSG mice were tail-vein inoculated with patient-derived AML cells (1 × 106 cells/mouse) and randomized to the treatments shown (n = 5/group). Blood counts were obtained periodically by tail-vein phlebotomy. Mice were euthanized for signs of distress. a Experiment schema; b Time-to-distress. Log-rank test. c Serial blood counts. Measured by Hemavet. Median ± IQR. d Bone marrow replacement by AML. Bone marrow human and murine CD45 + cells measured by flow-cytometry after euthanasia (time-points b). Median ± IQR. p value Mann–Whitney test two-sided. e DNMT1 was not depleted from AML cells at progression (timepoints b) but was depleted at time-of-response (bone marrow harvested at Day 63 in a separate experiment). Flow cytometry. f Pyrimidine metabolism gene expression in bone marrow AML cells. QRT-PCR using human gene specific primers, bone marrow harvested after euthanasia. p values versus vehicle, unpaired t-test, two-sided.

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