Chronic Lymphocytic Leukemia With Two B-Cell Populations of Discordant Light Chain Restrictions in Individual Patients: Parallel Development of Biclonal B-Cell Neoplasms or Clonal Evolution With Isotype Switch?. Issue 4 (7th February 2023)

• Record Type: Journal Article
• Authors: Zhao, Yue; Siddiqi, Imran; Wildes, Tyler J; McCracken, Jenna; Deak, Kristen; Rehder, Catherine; Wang, Endi
• Is Part Of: American journal of clinical pathology. Volume 159:Issue 4(2023)
• Page Start: 337
• Page End: 351
• Publication Date: 2023-02-07
• Subjects: Chronic lymphocytic leukemia -- Small lymphocytic lymphoma -- Biclonal -- Clonal evolution -- NOTCH1; Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqac165
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: Objectives: To evaluate clinicopathologic characteristics of biclonal chronic lymphocytic leukemia (CLL). Methods: Retrospectively analyze clinical data and pathologic features. Results: Ten cases were identified in which flow cytometry demonstrated an abnormal B-cell population with a CLL-like immunophenotype but showed no definitive light chain restriction. All had cytogenetic abnormalities detected, including seven with two CLL-related abnormalities. Four of these showed features suggestive of clonal evolution, all having del(13q) as a "stem-line" abnormality and three showing del(11q) as a "side-line" abnormality. Five (50%) cases demonstrated deleterious NOTCH1 mutations, in contrast to 11.8% in a control group of monoclonal CLL ( P < .05). Of the 10 patients, 5 received treatment, with good/partial response in three cases and therapeutic resistance in one case. The median treatment-free survival was estimated at 68 months. Conclusions: Despite a polytypic pattern of light chain expression, the neoplastic nature of biclonal CLL is suggested by a characteristic CLL phenotype and can be confirmed by cytogenetic and genomic analyses. The two clones with discordant light chain isotypes may share a "stem-line" cytogenetic abnormality, suggesting possible clonal evolution. Biclonal CLL is associated with NOTCH1 mutations, which may occur in a small subclone and gradually evolve in clonal size. Genomic analysis on light chain–sorted and/or chronologically collected samples may provide insight into clonal evolution in CLL.