Stem cells and hematological malignancies: Characterization and therapeutic targetingPublished 08-12-2009
Coordinating investigator: Bernard Payrastre
Program supported in 2008-2010
Example of CGH-array data resulting from hybridization of genomic DNA on Affymetrix GenomeWide SNP 6.0 chip.
Based on the karyotype, 2 deletions on chromosomes 9 and 20 corresponding to dic(9;20) were detected.
The relapses observed following chemotherapy for many hematological malignancies result from pathological stem cell populations. Isolation and characterization of these populations are required prior to transmission of the pathology by cell transplant in immunodeficient mice.
This program is carried out on acute myeloid leukemia (AML), large cell anaplastic lymphoma, chronic lymphoid leukemia (CLL), and multipla myeloma (MM).
The goal is to isolate, characterize and target some pathological stem cell population responsible for relapse in some hematological malignancies :
There is a leukemic stem cell population capable of initiating leukemia and responsible for the relapse. The project aims at setting up innovative treatments focused on this cell compartment and the development of animal models.
- Large cell anaplastic lymphoma
We will search for lymphomagenesis stem cell in cord blood cells using the detection of NPM-ALK and TPM3-ALK fusion transcripts that could be the first oncogenic event in a multistep lymphomagenesis process.
B-CLLs are the most frequent adult leukemias. The project aims at characterizing a side-population containing cancer stem cells in blood or bone marrow samples from patients, and studying their response to Rituximab and signaling pathway inhibitors.
This B lymphopathy is characterized by malignant plasma cell proliferation in the microenvironment containing mesenchymal stem cells (MSC) that are abnormal in these patients. The MSCs facilitate the myeloma cell growth and could be used as new therapeutic targets in MM treatment. The goal is to characterize these cells and to assess new molecules used in MM treatment on MSC abnormalities.
This program should improve the sorting, the characterization and the transplant of the stem cells with or without genetic modification, in immunodepressed mice in order to mimick the development of human pathologies.
New technologies will be transfered from expert laboratories (C. Eaves, Canada; D. Bonnet, UK; M.K. Brenner, USA) to scientific Toulouse teams.
Acute myeloid leukemia (AML), large cell anaplastic lymphoma, chronic lymphoid leukemia (CLL), multipla myeloma (MM), NPM-ALK, TPM3-ALK, Rituximab, mesenchymal stem cell.
Wide diversity of PAX5 alterations in B-ALL : a Groupe Francophone de Cytogenetique Hematologique study.
Coyaud E, Struski S, Prade N, Familiades J, Eichner R, Quelen C, Bousquet M, Mugneret F, Talmant P, Pages MP, Lefebvre C, Penther D, Lippert E, Nadal N, Taviaux S, Poppe B, Luquet I, Baranger L, Eclache V, Radford I, Barin C, Mozziconacci MJ, Lafage-Pochitaloff M, Antoine-Poirel H, Charrin C, Perot C, Terre C, Brousset P, Dastugue N, Broccardo C. Blood. 2010 Apr 15 ;115(15):3089-97.
- Engineer (2 years) - Naïs Prade-Houdellier
- missions (2 years) in expert laboratories (C. Eaves, Canada; D. Bonnet, UK; M.K. Brenner, USA).
Teams associated to this program