Methylation of the DPH1 promoter causes immunotoxin resistance in acute lymphoblastic leukemia cell line KOPN-8
X Hu, H Wei, L Xiang, O Chertov, AS Wayne, TK Bera… - Leukemia research, 2013 - Elsevier
Moxetumomab pasudotox (HA22) is an immunotoxin with an anti-CD22 Fv fused to a portion
of Pseudomonas exotoxin A that kills CD22 expressing ALL cells. HA22 produced significant
responses in some cases of ALL. To understand how to increase response rate, we isolated
HA22-resistant KOPN-8 cells and found that HA22 cannot inactivate elongation factor-2
(EF2) due to low levels of DPH1 RNA and protein. Resistance was associated with
methylation of the CpG island in the DPH1 promoter. 5-Azacytidine prevented resistance …
of Pseudomonas exotoxin A that kills CD22 expressing ALL cells. HA22 produced significant
responses in some cases of ALL. To understand how to increase response rate, we isolated
HA22-resistant KOPN-8 cells and found that HA22 cannot inactivate elongation factor-2
(EF2) due to low levels of DPH1 RNA and protein. Resistance was associated with
methylation of the CpG island in the DPH1 promoter. 5-Azacytidine prevented resistance …