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BC Cancer Agency Research Day 2017

Categories:
Colloquia
June 5, 2017 - 12:00pm

BC Cancer Agency Research Centre 675 W.10th Ave.

 


Room: 
Gordon & Leslie Diamond Family Theatre

Speaker

Keynote: Stem Cells in Human AML
Dr. Ravi Majeti
Associate Professor of Medicine, Division of Hematology, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
BC Cancer Agency Research Day 2017

Videolinked to:

FVC – room 2035, VIC room #3, CSI – Shuswap room,
Michael Smith Labs – room 226, C&W – Rm K4-142, CN- Salmon room

*A recording of this presentation can be viewed at:
PHSA network users: H:\EVERYONE\Presentations\CRC Noon Rounds Seminar Series\2017
BCCRC/GSC users: \\srvnetapp02\bcca\docs\EVERYONE\Presentations\CRC Noon Rounds Seminar Series\2017
(Please contact respective help desks (PHSA, BCCRC or GSC) if you need further assistance)

Keynote Speaker - Dr. Ravi Majeti

Department of Medicine, Division of Hematology, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
AML develops from the sequential acquisition of multiple mutations in a single lineage of cells. Given that all cells in the myeloid lineage, apart from HSC, are short-lived, we proposed a model in which serial acquisition of mutations occurs in HSC. We investigated this model through the analysis of AML and patient-matched residual HSC and identified multiple mutations in residual HSC, which we termed pre-leukemic mutations. Through single cell analysis, we determined that a clonal progression of mutations occurs in HSC, and we identified patterns of mutation acquisition supporting a model in which mutations in epigenomic genes occur early in the evolution of AML, while mutations in proliferative genes occur late. We identified pre-leukemic HSC in a larger cohort of AML patients and determined that their frequency varied widely from undetectable to nearly 100%. Stratifying these patients into high or low pre-leukemic HSC groups demonstrated that the high group had much worse overall and relapse-free survival, indicating that the presence of pre-leukemic HSC may be critical for clinical outcomes. In bulk AML, sequencing studies demonstrated that most cases harbor multiple subclones with a complex evolutionary structure. These subclones potentially exhibit distinct features including leukemia stem cell properties, clonal dominance, and responses to chemotherapy and targeted agents. Isolating and investigating these subclones is essential to understanding their properties, and is facilitated by a novel humanized ossicle xenotransplantation model and single cell methods. Eventually, all subclones must be targeted in order to improve long-term outcomes and for potential cures in AML.

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ResearchDay Poster V3 BCCA 2017.pdf175.06 KB
ResearchDay_Schedule BCCA 2017.pdf344.84 KB