Abstract:
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 (UCSF) will discuss 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 will also discuss a third study using DNA antibody sequencing (DAb-seq) on the Tapestri Platform to demonstrate immunophenotypic and genotypic evolution on AML treatment.
Register for this webinar to hear Dr. Smith will present her findings on the evolution of AML in response to FLT3i and chemotherapy treatment, in which multiple clones had distinct mechanisms of drug resistance. She will discuss the role of off-target (non-FLT3) mutations that activate downstream RAS–MAPK pathways as well as heterogeneity in FLT3 kinase domain (KD) mutations. Given the clinical relevance of these results, Dr. Smith will highlight the potential to use single-cell DNA sequencing to inform combination therapies and dynamic strategies for improved treatment of AML.
In this webinar, you will learn about:
Speaker bio:
Dr. Catherine Smith is a hematologist-oncologist who specializes in acute myeloid leukemia (AML), a rapidly spreading blood cancer. She is interested in AML with mutations in the FLT3 gene, which is involved in leukemia cell growth, division, and survival. Dr. Smith’s research focuses on understanding resistant/refractory AML and developing new treatment strategies.
