Clonal Trajectories and Cellular Mechanisms of Relapse in ALL

Journal Club:
Cancer Discovery & Blood Cancer Discovery with Dr. Charles G. Mullighan and Dr. John E. Dick

Moderated by: Tanya Bondar, PhD, Blood Cancer DiscoveryDeputy Editor
Recorded: 7/15/2020

Watch the recording of the AACR Virtual Journal Club: Cancer Discovery & Blood Cancer Discovery session, featuring John E. Dick, PhD, FRS of the University of Toronto and Charles G. Mullighan, MBBS (hons), MSc, MD of St. Jude Children’s Hospital, as they present their findings, published back-to-back, in Cancer Discovery & Blood Cancer Discovery: "Relapse-Fated Latent Diagnosis Subclones in Acute B Lineage Leukemia Are Drug Tolerant and Possess Distinct Metabolic Programs" and "Mutational Landscape and Patterns of Clonal Evolution in Relapsed Pediatric Acute Lymphoblastic Leukemia.”

Isolation and characterization of subclones from diagnosis samples of patients with B-ALL who relapsed showed that relapse-fated subclones had increased drug tolerance and distinct metabolic and survival transcriptional programs compared with other diagnosis subclones. Dr. John E. Dick’s study provides strategies to identify and target clinically relevant subclones before further evolution toward relapse.

Dr. Charles G. Mullighan’s study defines the landscape of mutations that preexist and arise after commencement of ALL therapy and shows that relapse may be propagated from ancestral, major, or minor clones at initial diagnosis. A subset of cases exhibit hypermutation that results in expression of neoepitopes that may be substrates for immunotherapeutic intervention.

Stay tuned for the Q&A session at the end of the recording.

About the Featured Speakers:

Charles G. Mullighan, MBBS (Hons), MSc, MD is the Deputy Director of the St. Jude Children’s Research Hospital Comprehensive Cancer Center and Co-Leader of the Cancer Center’s Hematological Malignancies Program. His research focuses on defining the landscape of genomic and epigenomic alterations that drive the pathogenesis of acute lymphoblastic leukemia (ALL) and related disorders and then using this information to develop experimental models that faithfully recapitulate the genetics of human ALL to gain mechanistic insights and advances in diagnosis and therapy.

John E. Dick, PhD, FRS is a Senior Scientist at the Princess Margaret Cancer Centre and Affiliate Faculty Member, McEwen Stem Cell Institute, University Health Network. He also serves as Professor of Molecular Genetics at the University of Toronto and is Co-Leader for the Acute Leukemia-Translational Research Initiative, Ontario Institute for Cancer Research, Toronto. His research enabled isolation and characterization of normal and leukemic human hematopoietic stem cells and progenitors at single-cell resolution, and provided direct evidence for the cancer stem cell hypothesis. His work is currently aimed at elucidating the origin and nature of cancer and development of new approaches to cancer therapy.