CRCM / IPC (UMR-1068)

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CRCM / IPC (UMR-1068)

The center de Recherche en Cancérologie de Marseille (CRCM) and the Institut Paoli-Calmettes (IPC) are two research entities based in Marseille. In the field of leukemias and related diseases, the CRCM-IPC addresses the following research themes: genomics, leukemogenesis, immune monitoring/immunotherapy, cell therapy, advanced therapy medicinal products (ATMP), personalized medicine, early phase trials.

Prof. Norbert Vey

Head of Entity

Contact

Email : yves.collette@inserm.fr

Cancer Research Center of Marseille
Inserm, CNRS, Aix-Marseille University,
Institut Paoli-Calmettes
27, boulevard Leï Roure BP 30059
13273 MARSEILLE CEDEX 09 - France

Website

Expertise Research areas Therapy Contributions Selection of publications Ecosystem

Myeloproliferative Neoplasms (MPN)
Mastocytosis
Inherited Bone Marrow Failure (BMF) syndromes
Acute Myeloid Leukemia (AML)
Myelodysplastic Syndromes (MDS)

Identification of basic concepts to understand mechanisms that maintain genome stability
Identification of basic concepts in cell polarity and cell signalling
Identification of mechanisms implicated in cell fate and epigenetics
Identification of mechanisms of host-tumor interactions and immunity
Identification and characterisation of mechanisms of oncogenesis/leukemogenesis
Identification of molecular signatures in AML, MDS and MPN and identification of biomarkers able to predict therapeutic success (or resistance)
Identification of therapeutic targets and their mechanisms of action, design of inhibitors in leukemia
Innovative clinical research in leukemias and chronic myeloid malignancies
Design of new therapeutical strategies and drugs
Bioinformatics

Targeted therapy
Gene therapy
Cell therapy
Immunotherapy
CAR-T cells

Scientific

Discovery of a new cell death pathway secondary to mitochondrial iron deprivation
FrPPI-Chem, a dedicated chemical library for protein-protein interaction inhibitor discovery
Repositioning and hit-to-lead optimization of a deoxycytidine kinase inhibitor.
Development of a new biomarker with potential for use in the diagnosis of Fanconi disease
Identification of an onco-metabolite as a circulating marker of aggressiveness in chronic inflammatory mast cell diseases
Identification of new markers of leukemia-initiating cells
Discovery and characterization of a non-canonical function of the epigenetic factor EZH2 in APL resistance
New molecular insight in tumor-stroma communication – the antitumoral function of stromal syntenin in AML

Medical

INA03 Phase I first in human clinical trial: INA03 is a conjugated monoclonal antibody developed by INATHERYS
HEMATO-BIO cohort: Non-interventional study of clinical and biological parameters of interest in patients with acute leukemia, myelodysplasia or myeloproliferative syndrome
First feasibility study of an integrated approach to genomic and drug sensitivity/resistance analyses designed to guide therapeutic strategy in real time in a cohort of refractory or relapsed AML patients

Leblanc R, Ghossoub R, Goubard A, Castellano R, Fares J, Camoin L, Audebert S, Balzano M, Bou-Tayeh B, Fauriat C, Vey N, Garciaz S, Borg JP, Collette Y, Aurrand-Lions M, David G, Zimmermann P. Downregulation of stromal syntenin sustains AML development. EMBO Mol Med 2023.
Saez-Ayala M, Hoffer L, Abel S, Ben Yaala K, Sicard B, Andrieu GP, Latiri M, Davison EK, Ciufolini MA, Brémond P, Rebuffet E, Roche P, Derviaux C, Voisset E, Montersino C, Castellano R, Collette Y, Asnafi V, Betzi S, Dubreuil P, Combes S, Morelli X. From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia. Nat Commun. 2023 May 29;14(1):3079. doi: 10.1038/s41467-023-38668-2. PMID: 37248212; PMCID: PMC10227015.
Collignon A, Hospital MA, Montersino C, Courtier F, Charbonnier A, Saillard C, D'Incan E, Mohty B, Guille A, Adelaïde J, Carbuccia N, Garnier S, Mozziconacci MJ, Zemmour C, Pakradouni J, Restouin A, Castellano R, Chaffanet M, Birnbaum D, Collette Y, Vey N. A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study. Blood Cancer J. 2020 Jun 3;10(6):64. doi: 10.1038/s41408-020-0330-5. PMID: 32488055; PMCID: PMC7266815.
Garciaz S, Guirguis AA, Müller S, Brown FC, Chan YC, Motazedian A, Rowe CL, Kuzich JA, Chan KL, Tran K, Smith L, MacPherson L, Liddicoat B, Lam EYN, Cañeque T, Burr ML, Litalien V, Pomilio G, Poplineau M, Duprez E, Dawson SJ, Ramm G, Cox AG, Brown KK, Huang DCS, Wei AH, McArthur K, Rodriguez R, Dawson MA. Pharmacologic Reduction of Mitochondrial Iron Triggers a Noncanonical BAX/BAK-Dependent Cell Death. Cancer Discov. 2022 Mar 1;12(3):774-791. doi: 10.1158/2159-8290.CD-21-0522. PMID: 34862195; PMCID: PMC9390741.
Poplineau M, Platet N, Mazuel A, Hérault L, N'Guyen L, Koide S, Nakajima-Takagi Y, Kuribayashi W, Carbuccia N, Haboub L, Vernerey J, Oshima M, Birnbaum D, Iwama A, Duprez E. Noncanonical EZH2 drives retinoic acid resistance of variant acute promyelocytic leukemias. Blood. 2022 Dec 1;140(22):2358-2370. doi: 10.1182/blood.2022015668. PMID: 35984905.
Zidi B, Vincent-Fabert C, Pouyet L, Seillier M, Vandevelde A, N'guessan P, Poplineau M, Guittard G, Mancini SJC, Duprez E, Carrier A. TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling. Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):211-216. doi: 10.1073/pnas.1809980116. Epub 2018 Dec 17. PMID: 30559202; PMCID: PMC6320535.
Pelletier J, Balzano M, Destin J, Montersino C, Delahaye MC, Marchand T, Bailly AL, Bardin F, Coppin E, Goubard A, Castellano R, de Bruijn MJW, Rip J, Collette Y, Dubreuil P, Tarte K, Broccardo C, Hendriks RW, Schiff C, Vey N, Aurrand-Lions M, Mancini SJC. Niche-expressed Galectin-1 is involved in pre-B acute lymphoblastic leukemia relapse through pre-B cell receptor activation. iScience. 2023 Mar 11;26(4):106385. doi: 10.1016/j.isci.2023.106385. PMID: 37009219; PMCID: PMC10060685.
Agopian J, Da Costa Q, Nguyen QV, Scorrano G, Kousteridou P, Yuan M, Chelbi R, Goubard A, Castellano R, Maurizio J, Teodosio C, De Sepulveda P, Asara JM, Orfao A, Hermine O, Dubreuil P, Brenet F. GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness. Blood. 2021 Oct 28;138(17):1590-1602. doi: 10.1182/blood.2020008948. PMID: 33974006.
Chretien AS, Devillier R, Granjeaud S, Cordier C, Demerle C, Salem N, Wlosik J, Orlanducci F, Gorvel L, Fattori S, Hospital MA, Pakradouni J, Gregori E, Paul M, Rochigneux P, Pagliardini T, Morey M, Fauriat C, Dulphy N, Toubert A, Luche H, Malissen M, Blaise D, Nunès JA, Vey N, Olive D. High-dimensional mass cytometry analysis of NK cell alterations in AML identifies a subgroup with adverse clinical outcome. Proc Natl Acad Sci U S A. 2021 Jun 1;118(22):e2020459118. doi: 10.1073/pnas.2020459118. PMID: 34050021; PMCID: PMC8179170.
Berrada S, Martínez-Balsalobre E, Larcher L, Azzoni V, Vasquez N, Da Costa M, Abel S, Audoly G, Lee L, Montersino C, Castellano R, Combes S, Gelot C, Ceccaldi R, Guervilly JH, Soulier J, Lachaud C. A clickable melphalan for monitoring DNA interstrand crosslink accumulation and detecting ICL repair defects in Fanconi anemia patient cells. Nucleic Acids Res. 2023 Aug 25;51(15):7988-8004. doi: 10.1093/nar/gkad559. PMID: 37395445; PMCID: PMC10450163.

National

European

OECI Network

International

Research infrastructures

Bioinformatics	CiBi, CRCM Integrative Bioinformatics platform.
Chemical synthesis	DOSynth, platform for organic molecule synthesis.
Nanobodies	Single domain antibody selection and screening platform (Nanobodies).
High Throughput Screening	HiTS/IPCdd, High Throughput Screening facility.
Immunomonitoring	PIC, immunomonitoring platform.
Cytometry	Flow cytometry and cell sorting.
Proteomics	MaP, Mass Spectrometry and Proteomic platform.
Microscopy	DNA repair and microscopy.
Culture cellulaire 3D	3D-Hub-O, platform for stem cell and organoïd medicine.
Pharmacokinetics	SMARTc, Simulation & Modeling for Adaptive Response to therapeutics in Cancer.
Histopathology	ICEP, Experimental Histo-Pathology Core Facility.
Preclinical studies	TrGET, preclinical platform.

Cellular therapy

Biotherapy

Clinical Biotherapy and Cellular Therapy Investigation Center.

Biobank

Biobank of CRCM.

Biological samples
Registry/Observatory AML	Biobank (>3,000 samples from AML patients at diagnosis and follow up).
Clinical trial AML MDS MPS	HEMATO-BIO-IPC 2013-015 (NCT02320656), prospective cohort of patients with AML, MDS, MPS at diagnosis, remission, or relapse (400 patients included).
Patient-derived xenografts AML ALL	Xenobank (>40 acute leukemia PDX).

Category	Models	Pathology	Specification	Sample type	Number of models	Genetics characterization
In vitro	CDX	APDCL	-	-	2	-
In vitro	CDX	T-ALL	-	-	3	-
In vitro	CDX	AML	-	-	10	-
In vitro	PDX	B-ALL	-	Diagnosis	4	All
In vitro	PDX	B-ALL	-	Relapse	4	All
In vitro	PDX	B-ALL	-	-	9	All
In vitro	PDX	AML	-	-	8	All
In vitro	PDX	AML	-	Relapse	14	All
In vitro	PDX	AML	-	Diagnosis	10	All
In vitro	Mouse tumor-derived cell line	AML	FLB1	-	-	-
In vitro	Mouse tumor-derived cell line	AML	C1498	-	-	-
In vivo	CDX	APDCL	-	-	2	-
In vivo	CDX	T-ALL	-	-	3	-
In vivo	CDX	AML	-	-	10	-
In vivo	Mouse model	AML	cMLL-AF9	-	-	-
In vivo	Mouse model	AML	iMLL-AF9 x Jam3 cKO	-	-	-
In vivo	PDX	AML	-	Relapse	14	All
In vivo	PDX	B-ALL	-	Diagnosis	4	All
In vivo	PDX	APDCL	-	-	4	None
In vivo	PDX	T-ALL	-	-	7	All
In vivo	PDX	B-ALL	-	-	9	All
In vivo	PDX	AML	-	Diagnosis	10	All
In vivo	PDX	B-ALL	-	Relapse	4	All
In vivo	PDX	AML	-	-	8	All

Partnership research offers

CLINICAL INVESTIGATION CENTER FOR THE SPONSORING AND CONDUCT OF PHASE I TO III INTERVENTIONAL CLINICAL TRIALS (ALL/AML/MPS/MDS)

CLINICAL INVESTIGATION CENTER FOR THE COORDINATION AND CONDUCT OF PHASE I TO III CLINICAL TRIALS IN LEUKEMIA AND RELATED DISEASES (AML, MPS, MDS, ALL)

PLATFORM FOR DEVELOPING AND IMPLEMENTING TESTS FOR PRECLINICAL VALIDATION IN VITRO, EX VIVO, AND IN VIVO (ACUTE LEUKEMIA)

PLATFORM FOR ACCELERATING THE DISCOVERY AND OPTIMIZATION OF NEW BIOACTIVE MOLECULES (ACUTE LEUKEMIA)