The kappa/lambda ratio of surface immunoglobulin light chain as a valuable parameter for MRD assessment in CLL with atypical immunophenotype

Sci Rep. 2024 Jun 11;14(1):13452. doi: 10.1038/s41598-024-64398-6.

Abstract

In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of highly effective therapeutic agents. Flow cytometry provides notable cost-effectiveness and immediacy, with an expected sensitivity level of approximately 10-4. The critical aspect of MRD detection via flow cytometry lies in accurately defining the region containing tumor cells. However, a subset of CLL, known as CLL with atypical immunophenotype, exhibits a distinct cell surface marker expression pattern that can make MRD detection challenging, because these markers often resemble those of normal B cells. To enhance the sensitivity of MRD detection in such atypical cases of CLL, we have capitalized on the observation that cell surface immunoglobulin (sIg) light chains tend to be expressed at a higher level in this subtype. For every four two-dimensional plots of cell surface markers, we used a plot to evaluate the expression of sIg kappa/lambda light chains and identified regions where the kappa/lambda ratio of sIg light chains deviated from a designated threshold within the putative CLL cell region. Using this method, we could detect atypical CLL cells at a level of 10-4. We propose this method as an effective MRD assay.

MeSH terms

  • Female
  • Flow Cytometry* / methods
  • Humans
  • Immunoglobulin Light Chains / metabolism
  • Immunoglobulin kappa-Chains*
  • Immunoglobulin lambda-Chains*
  • Immunophenotyping* / methods
  • Leukemia, Lymphocytic, Chronic, B-Cell* / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell* / pathology
  • Male
  • Neoplasm, Residual* / diagnosis

Substances

  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Immunoglobulin Light Chains