![Figure 1. Primary clinical resistance to PKC412 therapy in an AML patient with FLT3_ITD627E. (A) Serial counts of white blood cells (WBCs) and peripheral leukemic blasts at several time points during PKC412 therapy and at the time point of clinical resistance (day 35) are depicted. (B) Results of FLT3_ITD screening by PCR using genomic DNA from primary AML blasts before PKC412 therapy (baseline [BL]) and at the time point of primary resistance (progressive disease [PD]) at day 35 of PKC412 therapy. ITD1 and ITD2 indicate 2 different FLT3_ITD alleles. wt indicates wild-type FLT3. (C) Primary AML blasts isolated at the time of primary resistance (2 days after PKC412 had been discontinued), harboring the FLT3_ITD627E allele (A), were treated ex vivo with different concentrations of PKC412 for 1 hour. Tyrosine phosphorylation of FLT3 and STAT5 was analyzed by immunoblotting of cellular lysates.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/113/17/10.1182_blood-2007-11-126664/4/zh80140932980001.jpeg?Expires=1723734975&Signature=rYyiw9XwX-IgbGJZDdx94xpzpv92TmuAoOZysTBRs1V6ukB6enrOcyRPG8Fi-tgGqfcS~nMmfj2vwI1Ig67Vj6~b8os4zcGbwv5XgBQLQKVzPtRWVGkEYgGV3MwDQPGQf0ocX~0SZiyNQo4XPt02EAr~Gq~ekDRourV~3FikMZHinqZhF9vQaduxE5fYNt72ZA78TnFpagD3ks04qRgis5Y4mgAOIa-mjym6XQcSOHDumPc~QC-wqIJv~T3WgnnQnmIiBQ5kTqT2bCly3o~ICsWQMNIGdwrD2ix~1sRl43V8vo~VZ-wMMqAHAx2yQaPUs10m81TzXcvOTaTnNILQXA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Primary clinical resistance to PKC412 therapy in an AML patient with FLT3_ITD627E. (A) Serial counts of white blood cells (WBCs) and peripheral leukemic blasts at several time points during PKC412 therapy and at the time point of clinical resistance (day 35) are depicted. (B) Results of FLT3_ITD screening by PCR using genomic DNA from primary AML blasts before PKC412 therapy (baseline [BL]) and at the time point of primary resistance (progressive disease [PD]) at day 35 of PKC412 therapy. ITD1 and ITD2 indicate 2 different FLT3_ITD alleles. wt indicates wild-type FLT3. (C) Primary AML blasts isolated at the time of primary resistance (2 days after PKC412 had been discontinued), harboring the FLT3_ITD627E allele (A), were treated ex vivo with different concentrations of PKC412 for 1 hour. Tyrosine phosphorylation of FLT3 and STAT5 was analyzed by immunoblotting of cellular lysates.
