Open AccessClonal evolution in chronic lymphocytic leukemia is scant in relapsed but accelerated in refractory cases after chemo(immune) therapy
Author(s) -
Marc Zapatka,
Eugen Tausch,
Selcen Öztürk,
Deyan Y. Yosifov,
Martina Seiffert,
Thorsten Zenz,
Christof Schneider,
Johannes Blöhdorn,
Hartmut Döhner,
Daniel Mertens,
Peter Lichter,
Stephan Stilgenbauer
Publication year - 2021
Publication title -
haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.782
H-Index - 142
eISSN - 1592-8721
pISSN - 0390-6078
DOI - 10.3324/haematol.2020.265777
Subject(s) - somatic evolution in cancer , chronic lymphocytic leukemia , biology , leukemia , immunology , disease , immune system , oncology , cancer , genetics , medicine
Clonal evolution is involved in the progression of chronic lymphocytic leukemia (CLL). To link evolutionary patterns to different disease courses, we performed a long-term longitudinal mutation profiling study of CLL patients. Tracking somatic mutations and their changes in allele frequency over time and assessing the underlying cancer cell fraction revealed highly distinct evolutionary patterns. Surprisingly, in long-term stable disease and in relapse after long-lasting clinical response to treatment, clonal shifts are minor. In contrast, in refractory disease major clonal shifts occur although there is little impact on leukemia cell counts. As this striking pattern in refractory cases is not linked to a strong contribution of known CLL driver genes, the evolution is mostly driven by treatment-induced selection of sub-clones, underlining the need for novel, non-genotoxic treatment regimens.