Identification of biomarkers and therapeutic vulnerabilities

Uncovering the role of biomarkers in NUP98 acute megakaryoblastic leukemia

We identified genes encoding cell surface proteins that were upregulated in AMKL from synthetic models and patients and minimally expressed on normal hematopoietic stem/progenitor cells (HSPCs) (Blood Adv 2019; 3 (21): 3307–3321). Expression and function of novel AMKL biomarkers are being assessed in normal hematopoiesis and leukemia.

Funding: Leukemia & Lymphoma Society of Canada; S. Cellot lead PI; 2018-2020.

Towards a better risk-adapted therapy in young adults with acute myeloid leukemia

Benefiting from our biobanking partnership with the Quebec Leukemia Cell Bank, we contribute to a collaborative project focusing on the identification of specific genetic MRD (minimal residual disease) markers using transcriptome sequencing of leukemic cells from adolescent and young adult (AYA) AML patients and normal hematopoietic cells.

We are developing MRD clinical tests for the novel markers identified and performing functional studies to assess the therapeutic potential of these targets.

Funding: CCSRI-Cole Foundation; J. Hébert, S.Cellot co-PI & B.T. Wilhelm; 2018-2021.

Establishing a chemogenomic screening pipeline for high risk acute pediatric leukemias

As part of a multi-disciplinary team, we are conducting unbiased high throughput pharmacological screens using synthetic models and primary specimens of high risk pediatric leukemias, and normal cord blood cells to identify AML genotype specific therapeutic vulnerabilities.

The central aspect of this project is a small molecule screen that is performed at the Institute for Research in Immunology and Cancer (IRIC) high-throughput screening facility using a 12k library of structurally diverse molecules.

CRISPR based chemogenomic screens will also be performed to assess genetic dependencies for drug sensitivity, potentially opening new therapeutic strategies.

Funding: Oncopole EMC2; B.T. Wilhelm, S. Cellot co-lead PI, F. Barabé, A. Marinier, J.Hébert, M.Tyers, S. Lemieux, K.Eppert, and G.Sauvageau; 2018-2021.