[929] Cellular and Molecular Analysis Tools for Lymphoma and Leukemia Diagnosis
Current diagnosis of hematologic diseases like lymphomas or acute leukemias is based on a synthesis of various laboratory technologies: morphologic analyses using microscopes, immunophenotype analyses using flow cytometry, chromosome analyses using caryotyping and FISH, as well as genetic analyses using molecular biology techniques. In our group we develop new molecular methods for a better and more precise classification of leukemias and lymphomas.
Project 1: Leukemia and lymphoma diagnosis using nanotechnology
During the last ten years gene expression profiling (GEP) using microarray technology has emerged as a powerful method for better classification of disease entities, outcome prediction, pathway delineation, and identification of targets for therapeutic intervention in various haematological malignancies. In our project we establish prediction algorithms for the diagnosis and classification of acute leukemias and of B cell lymphomas using a new mRNA profiling system, more sensitive and precise than traditionnal microarrays, in combination with new mathematical analysis tools. In collaboration with a group at the Haute Ecole HEIG-VD at Yverdon we are developing supervised and non-supervised approaches based on fuzzy logic, in order to optimize the classification process for each patient.
Project 2: Leukemia and lymphoma diagnosis using High-throughput sequencing
With the advent of next-generation sequencing (NGS) methods the possibilities of analyzing the human genome have dramatically changed. As this technology is improving constantly and the cost decrease, analyzing patient samples becomes accessible to more and more laboratories and it can be foreseen that in the future NGS sequencing will allow to determine genomic alterations in unprecedented detail and precision, not only in diseases due to germline mutations, but as well in somatically acquired diseases and in particular in tumors. Sequencing a genome from a tumor cell presents nevertheless some difficulties (size and state of a sample, ploidy, clonal heterogeneity) and mutations are somatic and of a variable nature (point mutations, deletions, duplications, insertions/deletions, rearrangements,...), making it necessary to compare tumoral and constitutional genomes in a patient. Our project aims to develop NGS methods for leukemia, myelodysplastic syndrome and lymphoma samples using the capture technique to enrich for particular regions of the genome (transcription factors, cell cycle genes, apoptosis genes, adhesion molecules (see Point 3), ..), prior to sequencing.
Project 3: Analysis of the junctional adhesion molecule C (JAM-C) in normal and malignant B lymphocytes.
Junctional adhesion molecule C (JAM-C) is an adhesion molecule localized at the tight junction of cell/cell contacts. Among others, it is expressed in lymphatic organs, where it plays a role in the transendothelial migration of leucocytes. We have shown that this molecule is expressed on human B lymphocytes, and that its expression is restricted to precise differentiation steps in B cell maturation. Moreover, we have found that in B cell lymphomas JAM-C expression is disease-specific and thus constitutes a new marker for lymphoma diagnosis. We are currently investigating in a mouse model whether blocking JAM-C with anti-JAM-C antibodies or soluble ligands could inhibit B cell migration and lymphoma development in lymphoid organs and thus, whether targeting JAM-C could constitute a new therapeutic strategy, with JAM-C blocking as a treatment to prevent lymphoma cells from reaching supportive microenvironments in BM and spleen.
Project 1: Leukemia and lymphoma diagnosis using nanotechnology
During the last ten years gene expression profiling (GEP) using microarray technology has emerged as a powerful method for better classification of disease entities, outcome prediction, pathway delineation, and identification of targets for therapeutic intervention in various haematological malignancies. In our project we establish prediction algorithms for the diagnosis and classification of acute leukemias and of B cell lymphomas using a new mRNA profiling system, more sensitive and precise than traditionnal microarrays, in combination with new mathematical analysis tools. In collaboration with a group at the Haute Ecole HEIG-VD at Yverdon we are developing supervised and non-supervised approaches based on fuzzy logic, in order to optimize the classification process for each patient.
Project 2: Leukemia and lymphoma diagnosis using High-throughput sequencing
With the advent of next-generation sequencing (NGS) methods the possibilities of analyzing the human genome have dramatically changed. As this technology is improving constantly and the cost decrease, analyzing patient samples becomes accessible to more and more laboratories and it can be foreseen that in the future NGS sequencing will allow to determine genomic alterations in unprecedented detail and precision, not only in diseases due to germline mutations, but as well in somatically acquired diseases and in particular in tumors. Sequencing a genome from a tumor cell presents nevertheless some difficulties (size and state of a sample, ploidy, clonal heterogeneity) and mutations are somatic and of a variable nature (point mutations, deletions, duplications, insertions/deletions, rearrangements,...), making it necessary to compare tumoral and constitutional genomes in a patient. Our project aims to develop NGS methods for leukemia, myelodysplastic syndrome and lymphoma samples using the capture technique to enrich for particular regions of the genome (transcription factors, cell cycle genes, apoptosis genes, adhesion molecules (see Point 3), ..), prior to sequencing.
Project 3: Analysis of the junctional adhesion molecule C (JAM-C) in normal and malignant B lymphocytes.
Junctional adhesion molecule C (JAM-C) is an adhesion molecule localized at the tight junction of cell/cell contacts. Among others, it is expressed in lymphatic organs, where it plays a role in the transendothelial migration of leucocytes. We have shown that this molecule is expressed on human B lymphocytes, and that its expression is restricted to precise differentiation steps in B cell maturation. Moreover, we have found that in B cell lymphomas JAM-C expression is disease-specific and thus constitutes a new marker for lymphoma diagnosis. We are currently investigating in a mouse model whether blocking JAM-C with anti-JAM-C antibodies or soluble ligands could inhibit B cell migration and lymphoma development in lymphoid organs and thus, whether targeting JAM-C could constitute a new therapeutic strategy, with JAM-C blocking as a treatment to prevent lymphoma cells from reaching supportive microenvironments in BM and spleen.