THREE ORAL COMMUNICATION AWARDS
INSERM U1170, Gustave Roussy, Université Paris Saclay, GREX, Villejuif, France
Effect of the interferon alpha (IFN) and arsenic trioxide (As2O3) combination in the treatment of myeloproliferative neoplasms (MPN)
The aim of our project is to understand the mechanism of action of interferon alpha in the treatment of myeloproliferative neoplasms MPN. Our data show that arsenic trioxide increases the efficacy of interferon alpha by specifically targeting the JAK2V617F HSPC through a PML-dependent mechanism in a preclinical mouse model, in UT7 cell line and on progenitor cells from MPN patients
Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
Transposable elements enhance hematopoietic regeneration via immune signaling activation
Maintaining hematopoietic stem cells (Hscs) in a dormant state is necessary to maintain their long-term functionality and capacity for self-renewal. Our work has shown that, in response to stress, such as myeloablation, chromatin remodeling takes place in HSCs, leading to the transcription of transposable elements. These RNAs serve as ligands to the innate immune system receptor MDA5, which in turn triggers an immune response that removes the HSC from its dormancy to regenerate the hematopoietic system.
Cancer Research Center of Toulouse, INSERM U1037, CNRS ERL 5294, Université de Toulouse, Ligue Nationale Contre le Cancer, équipe labellisée 2016, Toulouse, France.
Ubiquitin-specific protease 7 is a master regulator of checkpoint kinase 1 and chemoresistance in Acute Myeloid Leukemia
By studying the function of the deubiquitinylase USP7 in acute myeloid leukemia (AML), we demonstrate that USP7 inhibition significantly reduces AML cell proliferation in vitro and in vivo, and increases AML cell death. Moreover, USP7 inhibition synergizes with cytarabine to kill AML cell lines and primary cells from patient. Finally, transcriptomic and single cell analysis showed that USP7 could represent a new predictive marker of resistance and relapse at diagnosis. Altogether, our data demonstrate that USP7 represents both a marker of resistance to chemotherapy, as well as a potential therapeutic target to overcome resistance to treatment in AML
FOUR POSTER PRICES
Luxembourg Institute of Health, Tumor Stroma Interactions, Department of Oncology, University of Luxembourg, Luxembourg
Role of regulatory T cells in Chronic Lymphocytic Leukemia
In our work, we are investigating in vivo and in vitro the role of two microenvironment-regulated transcription factors in the suppressive ability of regulatory T cells (or Tregs) during Chronic Lymphocytic Leukemia (CLL) development. To this purpose, we generated conditional knock-out mice lacking specific genes only in Tregs using Foxp3-Cre mice. Following the adoptive transfer of CLL cells in the conditional knock-out mice, we observed a delay in CLL development and an increased anti-tumor immune response compared to wild-type controls.
University of Tours EA 7501 GICC, CNRS ERL7001 LNOx, "Niche leucémique et métabolisme oxydatif" Tours, CNRS ERL 7001, CNRS GDR 3697 MicroNiT, Faculté de Médecine de Tours, Tours, France
Transcriptomic meta-analysis across AML cytogenetic subgroups identifies robust common prognostic signature
According to the ELN, genetic abnormalities are used to stratify AML patients into 3 favorable, intermediate and poor risk groups. To improve this genetic classification, prognostic signatures have been developed without really taking into account the leukemic subtype. In our work, we performed a large-scale meta-analysis after assembling available expression microarray data and identifying a list of genes commonly deregulated in the AML bone marrow compared to a healthy bone marrow, including potential new targets. We then showed that these common genes, associated with the proliferation and a blockade of differentiation, enable to obtain a prognostic signature regardless of age, genetic abnormalities, or LSC signature.
Team “Niche and Cancer in Hematopoiesis”, Inserm/CEA UMR1274, “Genetic Stability, Stem Cells and Radiations”, Fontenay-aux-Roses, France
Development of human ossicles in immune-deficient mice as an alternative to study normal human hematopoiesis and poor engrafting pathologic samples: the end of a long road?
My work focuses on modelling a human bone marrow niche in mice. We hypothesized that the contribution of a human medullary environment will refine the existing models by providing various factors necessary for the homing and growth of normal and pathological human hematopoietic cells recalcitrant to the graft. In my poster, I describe how I have established an experimental protocol that allows to form under the immunocompromised mouse skin a viable human bone marrow efficient, in still preliminary results, to promote human haematopoietic development after transplantation of CD34+ cord blood cells.
Inserm U1170 "Hématopoïèse normale et pathologique", Gustave Roussy Cancer Campus
Srsf2P95H co-occurrence limits Jak2V617F-induced myelofibrosis
The co-existence of JAK2 and SRSF2 gene mutations is found in patients with myelofibrosis and increases the risk of progression to acute leukemia. My thesis project is to study, in an in vivo model, the impact of the interaction of these two mutations on the development of spinal fibrosis, megakaryopoiesis and hematopoietic stem cell function.
A “QUICKFIRE” PRESENTATION AWARD
Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11, Institut Gustave Roussy, INSERM U1170
Intragenic young LINE-1 elements as (cis)-regulators of hematopoietic stem cell gene expression
We recently discovered a new mechanism responsible for the loss of HSC function during irradiation (IR) involving the L1md, a subfamily of young and active LINE-1 elements in mice. My thesis project studies the fact that L1md depression may be due to epigenetic defects induced by IR and involved in transcriptomic alterations in HSCs, and that thrombopoietin could protect the function of HSCs by preventing these effects .