Acute lymphoblastic leukemia (ALL) is aggressive leukemia that occurs most frequently in children and is characterized by the presence of few chromosomal rearrangements and additional mutations. In this webinar, the second in a “Meet the Authors” series, Jan Cools of the VIB Center for Cancer Biology in Leuven, Belgium will discuss the application of single-cell analysis to determine the clonal heterogeneity of the leukemia cells of ALL cases at diagnosis.
Dr. Cools’ lab used single-cell targeted DNA sequencing (Tapestri, Mission Bio) and single-cell RNA-sequencing (10x Genomics) to determine the clonal heterogeneity of the leukemia cells of 20 ALL cases at diagnosis and monitored the clonal evolution during chemotherapy treatment. Specifically, the lab designed a custom ALL panel and obtained accurate single-nucleotide variant and small insertion-deletion mutation calling for 305 amplicons covering 110 genes in about 4400 cells per sample and time point. Bone marrow and/or blood samples from 12 B-cell ALL and eight T-cell ALL patients were analyzed.
Dr. Cools will discuss how single-cell DNA amplicon sequencing is a sensitive assay to detect clonal architecture and evolution of the malignant cells in ALL, and present his findings published in the Blood paper, “Single-cell DNA amplicon sequencing reveals clonal heterogeneity and evolution in T-cell acute lymphoblastic leukemia.”
Jan Cools obtained his doctorate in 2001 from the KU Leuven with a study on chromosomal defects in leukemia. From 2001 to 2003, he continued his research on the genetic causes of leukemia at Harvard Medical School. After his return to Belgium, he was promoted to assistant professor in 2005 and full professor in 2009 at KU Leuven. Cools is a group leader of VIB since 2008.
Cools’ research team studies the genetic complexity of acute lymphoblastic leukemia (ALL) and uses that information to develop novel models and treatment strategies. The group uses next-generation sequencing and single-cell sequencing to obtain a detailed view of the heterogeneity of ALL at diagnosis and its evolution during therapy. Based on these genetic insights, cell and mouse models are being generated to study the mechanisms’ contribution to leukemia development.
Cools has served as a board member of the European Hematology Association and has been the editor-in-chief of the open-access journal Haematologica from 2012 to 2017. He is currently editor-in-chief of HemaSphere, a new open-access hematology journal of the European Hematology Association.