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Clonal dynamics in a composite chronic lymphocytic leukemia and hairy cell leukemia‐variant
Author(s) -
Locher Maurus,
Jukic Emina,
Bohn JanPaul,
Untergasser Gerold,
Steurer Michael,
Cramer Christian Andreas,
Schwendinger Simon,
Vogi Verena,
Verdorfer Irmgard,
WitschBaumgartner Martina,
Nachbaur David,
Gunsilius Eberhard,
Wolf Dominik,
Zschocke Johannes,
Steiner Normann
Publication year - 2021
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22925
Subject(s) - somatic evolution in cancer , clone (java method) , chronic lymphocytic leukemia , hairy cell leukemia , leukemia , biology , lymphoma , cancer research , follicular lymphoma , ighv@ , mutation , immunology , cancer , genetics , gene
Composite lymphoma is the rare simultaneous manifestation of two distinct lymphomas. Chronic lymphocytic leukemia (CLL) has a propensity for occurring in composite lymphomas, a phenomenon that remains to be elucidated. We applied cytogenetics, droplet digital polymerase chain reaction, and massively parallel sequencing to analyze longitudinally a patient with CLL, who 3 years later showed transformation to a hairy cell leukemia‐variant (HCL‐V). Outgrowth of the IGHV4‐34‐ positive HCL‐V clone at the expense of the initially dominant CLL clone with trisomy 12 and MED12 mutation started before CLL‐guided treatment and was accompanied by a TP53 mutation, which was already detectable at diagnosis of CLL. Furthermore, deep sequencing of IGH showed a composite lymphoma with presence of both disease components at all analyzed timepoints (down to a minor clone: major clone ratio of ~1:1000). Overall, our analyses showed a disease course that resembled clonal dynamics reported for malignancies with intratumoral heterogeneity and illustrate the utility of deep sequencing of IGH to detect distinct clonal populations at diagnosis, monitor clonal response to therapy, and possibly improve clinical outcomes.

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