Emergence of IGH::CCND1 rearrangement and mutations in TP53, BTK, and BCL2 associated with therapy resistance in chronic lymphocytic leukemia

Abstract Chronic lymphocytic leukemia (CLL) is an indolent low‐grade B‐cell neoplasm that generally responds well to treatment. Rarely, CLL cases exhibit an IGH::CCND1 rearrangement, presenting a diagnostic challenge in distinguishing between clonal evolution within CLL and an independent mantle cel...

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Main Authors: Qing Wei, Hong Fang, James M. Jing, Roman Segura‐Rivera, L. Jeffrey Medeiros, Wei Wang
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:eJHaem
Subjects:
Online Access:https://doi.org/10.1002/jha2.1024
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author Qing Wei
Hong Fang
James M. Jing
Roman Segura‐Rivera
L. Jeffrey Medeiros
Wei Wang
author_facet Qing Wei
Hong Fang
James M. Jing
Roman Segura‐Rivera
L. Jeffrey Medeiros
Wei Wang
author_sort Qing Wei
collection DOAJ
description Abstract Chronic lymphocytic leukemia (CLL) is an indolent low‐grade B‐cell neoplasm that generally responds well to treatment. Rarely, CLL cases exhibit an IGH::CCND1 rearrangement, presenting a diagnostic challenge in distinguishing between clonal evolution within CLL and an independent mantle cell lymphoma. We report a case of CLL with the emergence of an IGH::CCND1 rearrangement and mutations associated with treatment resistance, including TP53, BTK, and BCL2, during disease progression. Immunophenotypic, cytogenetic, and molecular analyses support that these alterations are secondary events within the CLL clone. This case demonstrates dynamic clonal selection and expansion in response to treatments, which, in turn, contributes to treatment resistance.
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publishDate 2024-12-01
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spelling doaj-art-82c0ea75858a45b3a9801f39dfe1bef22025-08-20T01:56:52ZengWileyeJHaem2688-61462024-12-01561265126810.1002/jha2.1024Emergence of IGH::CCND1 rearrangement and mutations in TP53, BTK, and BCL2 associated with therapy resistance in chronic lymphocytic leukemiaQing Wei0Hong Fang1James M. Jing2Roman Segura‐Rivera3L. Jeffrey Medeiros4Wei Wang5Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USADepartment of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USADepartment of Abdominal Imaging The University of Texas MD Anderson Cancer Center Houston Texas USADepartment of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USADepartment of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USADepartment of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USAAbstract Chronic lymphocytic leukemia (CLL) is an indolent low‐grade B‐cell neoplasm that generally responds well to treatment. Rarely, CLL cases exhibit an IGH::CCND1 rearrangement, presenting a diagnostic challenge in distinguishing between clonal evolution within CLL and an independent mantle cell lymphoma. We report a case of CLL with the emergence of an IGH::CCND1 rearrangement and mutations associated with treatment resistance, including TP53, BTK, and BCL2, during disease progression. Immunophenotypic, cytogenetic, and molecular analyses support that these alterations are secondary events within the CLL clone. This case demonstrates dynamic clonal selection and expansion in response to treatments, which, in turn, contributes to treatment resistance.https://doi.org/10.1002/jha2.1024CLLIGH:CCND1 rearrangementmutationstherapy‐resistance
spellingShingle Qing Wei
Hong Fang
James M. Jing
Roman Segura‐Rivera
L. Jeffrey Medeiros
Wei Wang
Emergence of IGH::CCND1 rearrangement and mutations in TP53, BTK, and BCL2 associated with therapy resistance in chronic lymphocytic leukemia
eJHaem
CLL
IGH:CCND1 rearrangement
mutations
therapy‐resistance
title Emergence of IGH::CCND1 rearrangement and mutations in TP53, BTK, and BCL2 associated with therapy resistance in chronic lymphocytic leukemia
title_full Emergence of IGH::CCND1 rearrangement and mutations in TP53, BTK, and BCL2 associated with therapy resistance in chronic lymphocytic leukemia
title_fullStr Emergence of IGH::CCND1 rearrangement and mutations in TP53, BTK, and BCL2 associated with therapy resistance in chronic lymphocytic leukemia
title_full_unstemmed Emergence of IGH::CCND1 rearrangement and mutations in TP53, BTK, and BCL2 associated with therapy resistance in chronic lymphocytic leukemia
title_short Emergence of IGH::CCND1 rearrangement and mutations in TP53, BTK, and BCL2 associated with therapy resistance in chronic lymphocytic leukemia
title_sort emergence of igh ccnd1 rearrangement and mutations in tp53 btk and bcl2 associated with therapy resistance in chronic lymphocytic leukemia
topic CLL
IGH:CCND1 rearrangement
mutations
therapy‐resistance
url https://doi.org/10.1002/jha2.1024
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