Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy characterized by the overproduction of abnormal myeloblasts. Gene mutation-targeted therapies are a treatment option for patients with relapsed/refractory AML. For patients with FLT3 mutated AML, the FLT3 inhibitors (FLT3i), gilteritinib and quizartinib, can improve patient outcomes.
However, the development of secondary resistance to these drugs remains a major challenge. The acquisition of new mutations and the emergence of new subclones during the course of therapy can drive relapse. Although conventional bulk DNA sequencing can be used to identify the mutations in an entire sample, it cannot identify the mutations present in individual clones. Rather, deciphering the mechanisms of resistance to these drugs requires the dissection of AML at a single-cell level.
In this webinar, Dr. Catherine Smith, MD from the University of California, San Francisco discusses two studies that uncover mechanisms of resistance to gilteritinib and quizartinib. In both studies, Dr. Smith’s lab used serial single-cell DNA sequencing (using Mission Bio’s Tapestri Platform) to assess the clonal architecture of AML through treatment. She also discusses a third study using DNA antibody sequencing (DAb-seq) on the Tapestri Platform to demonstrate immunophenotypic and genotypic evolution on AML treatment.