The <i>EBF1-PDGFRB</i> T681I mutation is highly resistant to imatinib and dasatinib <i>in vitro</i> and detectable in clinical samples prior to treatment

Abstract

Not available.

Tyrosine kinase inhibitor response of ABL-class acute lymphoblastic leukemia: the role of kinase type and SH3 domain

“… 16 In contrast to our data, previous studies have suggested sensitivity to dasatinib in Ba/F3 models expressing PDGFRB -fusions. 4 , 60 , 61 Moreover, various case reports of patients with PDGFRB -fused ALL indicated a response to dasatinib. 5 , 35 , 40 However, multiple studies using kinase selectivity assays have shown a lower affinity of dasatinib for wild-type PDGFRB than for BCR::ABL1 or wild-type ABL1.…”

Genomics and precision medicine in pediatric acute lymphoblastic leukemia

“…There is a growing body of clinical evidence from case reports or small patient series to confirm the preclinical efficacy of ABL and JAK inhibitors in Ph-like ALL [86][87][88] . Preclinical and clinical reports have also demonstrated the sensitivity of NTRK inhibitor, larotrectinib, or ALK inhibitor, crizotinib, for the rare ETV6-NTRK3 Ph-like ALL [19,89,90] . Recently, mutations conferring resistance to imatinib and dasatinib have been identified in relapsed EBF1-PDGFRB Ph-like ALL, raising the necessity to monitor kinase domain mutations over the course of therapy to guide TKI selection [91] .…”

Detection of <I>ABL1</I> kinase domain mutations in therapy-naïve <I>BCR-ABL1</I>-positive acute lymphoblastic leukemia

“…They identified the mutation in three of 23 patients prior to treatment. 12 We speculate that mutations which confer resistance but reduce kinase activity or transformative capacity would not outgrow before TKI treatment and therefore only a subset of resistance mutations can exist in therapy-naïve patients. The high turnover rate of ALL cells should allow a much faster selection of mutated clones with a relative growth advantage if compared to the situation in chronic myeloid leukemia.…”