Page 161 - Haematologica May 2020

Resistance to Notch1 neutralizing antibody
Supplementary Figure S8-9), but with a higher level of down-regulation compared to OMP52M51 resistant cells (Online Supplementary Figure S10), suggesting that the inhibitory effect of the antibody on signaling is partially lost when resistance develops.
A
Resistance to OMP52M51 is associated with rewiring of lipid metabolism in PDTALL19 cells
These results prompted investigation of the effects of Notch blockade on lipid metabolism. To this end, we per- formed tandem mass spectrometry (MS/MS) for different
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C
Figure 2. Serial transplantation experiments disclose different phenotypic traits of resistance. (A) Outline of the experiment. Resistant cells were recovered from the spleen of OMP52M51-treated mice and injected into naїve mice (5-6 mice/group). Recipient mice were then treated weekly with OMP52M51 or control mono- clonal antibodies (Ctrl mAb) according to the standard protocol. (B) Kaplan-Meier survival curves of PDTALL8, PDTALL1 and PDTALL19 mice after a second course of treatment with OMP52M51. In these experiments, mice transplanted with PDTALL8, PDTALL11 or PDTALL19 resistant cells from the first round of treatment (PDTALL8: P=0.0441; PDTALL11: P<0,001; PDTALL19: P=0.00181 log-rank test). (C) Expression levels of selected Notch target genes in T-ALL cells obtained from the spleen of mice after the second course of OMP52M51 treatment (*P<0,05; **P<0,001. Mean ± standard deviation [SD], 3-6 samples/group).
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