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| Item Type: | Article |
|---|---|
| Title: | Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia |
| Creators Name: | Herling, C.D., Abedpour, N., Weiss, J., Schmitt, A., Jachimowicz, R.D., Merkel, O., Cartolano, M., Oberbeck, S., Mayer, P., Berg, V., Thomalla, D., Kutsch, N., Stiefelhagen, M., Cramer, P., Wendtner, C.M., Persigehl, T., Saleh, A., Altmüller, J., Nürnberg, P., Pallasch, C., Achter, V., Lang, U., Eichhorst, B., Castiglione, R., Schäfer, S.C., Büttner, R., Kreuzer, K.A., Reinhardt, H.C., Hallek, M., Frenzel, L.P. and Peifer, M. |
| Abstract: | 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, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we 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. |
| Keywords: | Heterocyclic Bridged Bicyclo Compounds, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p18, Neoplasm Drug Resistance, B-Cell Chronic Lymphocytic Leukemia, Mutation, Neoplasm Proteins, Sulfonamides / Therapeutic Use |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 9 |
| Number: | 1 |
| Page Range: | 727 |
| Date: | 20 February 2018 |
| Official Publication: | https://doi.org/10.1038/s41467-018-03170-7 |
| PubMed: | View item in PubMed |
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