Dear Students and Colleagues,

You are cordially invited to the lecture of MU Life Sciences Seminar:

"Dissecting the Interplay Between Genetic Lesions and the Tumor Microenvironment in Chronic Lymphocytic Leukemia"
by Dr. Dimitar Efremov at International Centre for Genetic Engineering and Biotechnology, Trieste, Italy

WHEN: Thursday, March 9, 2023 at 16:00.
WHERE: Seminar room 132, pavilion B11, University Campus Bohunice

Don't forget to bring your ISIC card to the lecture.

The announcement is published also here.

PhD students who would like to attend a sponsored lunch with Dr. Efremov (Thursday, at 12:00 at Campus River) please register by Wednesday March 8, 2023 using the form at the website above.

With best regards,
Linda Nosková
MU LSS administrator
noskova@sci.muni.cz

About the lecture

Chronic lymphocytic leukemia (CLL) is a common B cell malignancy characterized by the progressive accumulation of autoreactive B lymphocytes that are driven to expand by a complex interplay of genetic lesions and signals that the leukemic cells receive from the tumor microenvironment. Recent large-scale next generation sequencing studies have shown that the genetic landscape in CLL is highly heterogeneous, with point mutations or copy number alterations detected in more than 200 putative CLL driver genes. However, with few exceptions, the majority of the genetic lesions are relatively infrequent and their role during leukemia development, progression, transformation, and their impact on response to treatment are still unknown. Moreover, in vivo models to study how these genetic lesions cooperate between themselves and how they cooperate with signals from the tumor microenvironment are largely lacking. To facilitate such studies, we recently developed a CRISPR/Cas9-editing approach that allows for simultaneous introduction of mutations in multiple putative CLL driver genes in normal or leukemic murine B cells as well as genetic disruption of intracellular pathways that propagate microenvironmental signals in murine CLL cells or human Richter Syndrome patient-derived xenografts. The genetically modified cells are then transplanted in recipient mice to investigate how individual genetic lesions or microenvironmental signals affect the growth of the leukemic cells in vivo and how they influence the response to treatment with novel targeted therapies. We have used this procedure in two recent studies to show that recurrent genetic lesions in TP53 and the cell cycle inhibitors CDKN2A and CDKN2B cooperate with B cell receptor signals during Richter Transformation (Chakraborty S et al, Blood 2021) and to define the microenvironmental signals that are most relevant for the growth of xenografted patient-derived Richter Syndrome cells in vivo (Martines C et al, Blood 2022). The results from these and ongoing studies investigating additional genetic lesions will be presented in this talk.