Single Cell Sequencing of Polyclonal Resistance to FLT3 Inhibitors in AML
Catherine Smith, MD
Monday, April 23, 2018
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Chapters
Introduction
FLT3: The Most Frequently Mutated Gene in AML
FLT3 Mutations in AML
FLT3 KD Mutations are the Most Frequently Described Resistance Mechanism in Patients
On-Target and Off-Target Resistance: Mutually Exclusive?
ASP2215 (GILTERITINIB): A Type I AXL/FLT3 Inhibitor
ASP2215 Achieves >40%CRC in R/R FLT3 Mutant AML
Study Design
Acquired Somatic Mutations
Resistance Mechanisms to FLT3 Inhibitors: Role of Clonal Heterogeneity
Resistance Mechanisms to FLT3 Inhibitors: Clonal Heterogeneity
NRAS Mutations Confer Resistance to GILTERITINIB
Tapestri Analysis UCSF 4169
Tapestri Analysis PENN 4885
Tapestri Analysis PENN 5475
Longitudinal Analysis Reveals Preexisting Resistant Clones
Single-Cell Analysis Can Uniquely Inform Therapy
Summary: Clinical Resistance to FLT3 Inhibitors
Acknowledgements
Audience Questions
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