cancer-stem-cells-2019-scientifictracks

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Cancer Stem Cells 2019

Journal of Medical Oncology andTherapeutics | Volume 4

July 18-19, 2019 | Valencia, Spain

OF EXCELLENCE

IN INTERNATIONAL

MEETINGS

YEARS

CANCER STEM CELLS AND

ONCOLOGY RESEARCH

International Conference on

ERG ENHANCER-BASED REPORTER IDENTIFIES LEUKEMIA CELLS WITH ELEVATED LEU-

KAEMOGENIC POTENTIAL DRIVEN BY ERG-USP9X FEED-FORWARD REGULATION

Nasma Aqaqe-Tibi, Muhammad Yassin, Abed Alkader Yassin, Eitan Kugler, Eric R Lechman,

Olga I Gan, Amanda Mitchell, John E Dick, Shai Izraeli

and

Michael Milyavsky

Tel Aviv University, Israel

cute leukaemia is a rapidly progressing blood cancer with low survival rates. Unfavorable prognosis is at-

tributed to the insufficiently characterized subpopulation of leukemia stem cells (LSCs) that drive chemo

resistance and leukemia relapse. Here authors utilized a genetic reporter which enables stemness assessment

to enrich and functionally characterize LSCs. They revealed heterogeneous activity of the ERG+85 enhancer

based fluorescent reporter in human leukemias. Cells with high reporter activity (tag BFP High) exhibited el-

evated expression of stemness and chemo-resistance genes, demonstrated increased clonogenicity and re-

sistance to chemo and radio-therapy as compared to their tag BFP Neg counterparts. Moreover, tag BFP high

enriched fraction was capable of regenerating the original cellular heterogeneity and demonstrated increased

invasion ability. Most importantly, tag BFP High fraction was enriched for leukemia initiating cells in a xenograft

assay. They also identified USP9X deubiquitinase enzyme as a novel ERG transcriptional target that sustains

ERG+85 positive cells. Therapeutic targeting of USP9X led to the preferential inhibition of the ERG-dependent

leukemias. In summary, they have developed a new strategy to characterize LSCs and propose ERG targeting

via USP9X inhibition as a potential anti-leukaemia treatment.

Nasma Aqaqe-Tibi et al., J Med Oncl Ther 2019, Volume 4

Nasma Aqaqe-Tibi is a fourth year PhD student at Tel-Aviv University, currently working on characterization of gene regulatory net-

works responsible for human leukemia cells regeneration after genotoxic stress at Dr Milyavsky lab.

BIOGRAPHY