Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia.
Carmen D HerlingNima AbedpourJonathan WeissAnna SchmittRon Daniel JachimowiczOlaf MerkelMaria CartolanoSebastian OberbeckPetra MayerValeska BergDaniel ThomallaNadine KutschMarius StiefelhagenPaula CramerClemens-Martin WendtnerThorsten PersigehlAndreas SalehJanine AltmüllerPeter NürnbergChristian PallaschViktor AchterUlrich LangBarbara EichhorstRoberta CastiglioneStephan C SchäferReinhard BüttnerKarl-Anton KreuzerHans Christian ReinhardtMichael HallekLukas P FrenzelMartin PeiferPublished in: Nature communications (2018)
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.