Clonal dynamics in cancer under therapeutic pressure

02/20/2018

Martin Peifer and his team analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax

Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, Martin Peifer and his team analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. The work has been published in Nature Communications.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world with a diverse clinical course and a substantial degree of inter- and intra-patient heterogeneity. Ongoing clonal evolution is sought to be a key mechanism for the development of treatment-resistant or -refractory CLL and is, therefore, limiting treatment success and duration.

Martin Peifer and his co-worker report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions.

Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia
Herling CD, Abedpour N, Weiss J, Schmitt A, Jachimowicz RD, Merkel O, Cartolano M, Oberbeck S, Mayer P, Berg V, Thomalla D, Kutsch N, Stiefelhagen M, Cramer P, Wendtner CM, Persigehl T, Saleh A, Altmüller J, Nürnberg P, Pallasch C, Achter V, Lang U, Eichhorst B, Castiglione R, Schäfer SC, Büttner R, Kreuzer KA, Reinhardt HC, Hallek M, Frenzel LP, Peifer M. 
Nat Commun. 2018 Feb 20;9(1):727

 

For further information, please contact:
Dr. Martin Peifer
Translational Genomics, Faculty of Medicine and
Center for Molecular Medicine Cologne - CMMC Project A9 and CAP 6
University of Cologne

mpeifer[at]uni-koeln.de