Malignant progenitors from @entity1 with @entity10431 + XXXX are sensitive to a diphtheria toxin-urokinase fusion protein.

@entity1 @entity2212 @entity137 @entity10431 @entity706 @entity5 @entity6130 @entity3052 @entity1778 @entity1860
In previous studies, we demonstrated that the diphtheria toxin-urokinase fusion protein DTAT was selectively toxic to @entity3052 ( @entity3052 ) cell lines overexpressing the @entity10431 urokinase receptor. In the present study, we analyzed the sensitivity of @entity1 leukemic progenitors to DTAT and correlated the sensitivity with @entity10431 expression. We isolated @entity1778 by density gradient centrifugation and performed immunophenotyping by flow cytometry and blast sensitivity measurements by inhibition of cell proliferation and colony formation in semisolid media. We found @entity10431 overexpression in 18 (25%) of 71 @entity1 leukemic blast samples, including 18 (28%) of 64 @entity5 and 0 (0%) of 7 @entity706 . DTAT was toxic to @entity1 @entity1778 by both proliferation inhibition (IC50 <or=1 nM DTAT in 18/69 evaluable samples) and colony formation inhibition (>85% inhibition by 10 nM DTAT in 11/41 evaluable samples). Only @entity3052 and @entity1860 ( @entity1860 ) blast crisis blasts (18/61 [30%]) were sensitive to DTAT by the proliferation inhibition assay. @entity706 and @entity2212 ( @entity6130 ) progenitors were insensitive to DTAT by the proliferation inhibition assay (n = 7 and n = 3, respectively). Similarly, normal marrow progenitors were insensitive to DTAT by both proliferation inhibition (n = 2) and colony inhibition (n = 5) assays. The DTAT @entity137 measured by both proliferation inhibition assay and colony inhibition assay correlated with @entity10431 density (p < 0.0001 and p = 0.001, respectively). DTAT @entity137 results were similar for @entity1778 measured by either of the two assays (p = 0.0002). This study provides the first evidence that a urokinase receptor targeted diphtheria fusion protein is toxic to @entity1 @entity3052 blasts. The work also suggests that blast proliferation assays yield similar responses to @entity1778 colony-forming cell colony assays.
