Team 4 – Research project

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Third French Symposium on CART cell (CARTday)
January 17th,2019

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FACTORS OF PERSISTENCE OF LEUKEMIC CELLS TEAM

RESEARCH PROJECT

Eradication of the last tumor cell has been the holy grail of cancer research for decades. The idea was that if only a few persistent cancer cells remain in the body, relapse would inevitably occur. Thus, understanding the mechanisms that allow for the long-term persistence of these cells would help to avoid relapses. To address the question of persistence in human leukemia, we have built our research team around three strategic scientific axes.

The first axis investigated by Bruno Quesnel, Yasmine Touil, Thierry Idziorek, Carine Brinster, Céline Berthon and Sylvie Zouitina was aimed at discovering, using experimental models and patient cohorts, factors that govern tumor dormancy and long term persistence of minimal residual disease (MRD) in leukemia and multiple myeloma. Results have specifically pinpointed the role of immunoescape (PD-L1, CCL2) and stemness in tumor dormancy. More recently, the theme has been extended to tumor metabolism with the expertise of Philippe Marchetti and Jerome Kluza, which investigated dormance/resistance of leukemia cells under tyrosine kinase inhibitors.

The second axis explored by Claude Preudhomme, Catherine Roche-Lestienne, Stéphanie Poulain, Meyling Cheok, Olivier Nibourel, Christophe Roumier, Alice Marceau, and Nicolas Duployez, was dedicated to the systematic evaluation of new genomic markers of prognosis in hematological malignancies, notably AML, MDS, and Waldenstrom’s disease. The characterization of potential predictive markers of treatment failure and relapse in hematological malignancies has to yield results that can be easily translated into the daily routine. Biobanking of numerous national prospective clinical trials, is done in our team at the tumor cell bank. This axis has recently evolved under the impulsion of Meyling Cheok toward more functional characterization of leukemia cells, such as drug resistance and leukemia stemness, which are currently investigated in prospective patient cohorts from national study group such as ALFA and GFM.

The third axis investigates new therapeutic strategies to target MRD: Marie-Hélène David develops new drugs that target transcription factor/DNA interaction, notably HOXA9. Xavier Thuru elaborates new methods (i.e MST) in collaboration with chemists to target protein/protein interaction in dormant tumor cells. In 2016, Salomon Manier joined our team after five years at Irene Ghobrial lab at Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. He specifically investigates Myc targeting in Multiple Myeloma.