Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2020 Dec;108(6):1851-1857.
doi: 10.1002/JLB.5TA0320-411RR. Epub 2020 Apr 17.

A novel flow cytometry-based assay to measure compromised B cell receptor signaling as a prognostic factor in chronic lymphocytic leukemia

Jonas S Heitmann  1   2 , Melanie Märklin  2 , Felicia M Truckenmüller  1 , Clemens Hinterleitner  1 , Daniela Dörfel  3 , Michael Haap  4 , Hans-Georg Kopp  5 , Stefan Wirths  1 , Martin R Müller  1   3
Affiliations
Clinical Trial

A novel flow cytometry-based assay to measure compromised B cell receptor signaling as a prognostic factor in chronic lymphocytic leukemia

Jonas S Heitmann et al. J Leukoc Biol. 2020 Dec.

Abstract

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. In the past years, new therapeutic approaches (e.g., ibrutinib or venetoclax) have been established and greatly improved treatment of CLL. However, complete control or cure of the disease have not been reached so far. Thus, reliable prognostic markers are an imperative for treatment decisions. Recent studies have revealed an essential role for B cell receptor (BCR) signaling in the pathogenesis, prognosis, and therapy of CLL. A heterogeneous response to receptor stimulation with anti-IgM treatment culminating in different calcium flux capabilities has been demonstrated by several authors. However, the methods employed have not reached clinical application. Here, we report on a flow cytometry-based assay to evaluate calcium flux capabilities in CLL and demonstrate that compromised BCR signaling with diminished calcium flux is associated with a significantly better clinical outcome and progression free survival. In summary, our data strongly support the role of compromised BCR signaling as an important prognostic marker in CLL and establish a novel diagnostic tool for its assessment in clinical settings.

Keywords: BCR signaling; CLL; calcium flux; flow cytometry; prognosis.

PubMed Disclaimer

References

REFERENCES

    1. Byrd JC. Introduction to a series of reviews on chronic lymphocytic leukemia. Blood. 2015;126:427.
    1. Parikh SA. Chronic lymphocytic leukemia treatment algorithm 2018. Blood Cancer. 2018;J 8:93.
    1. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131:2745-2760.
    1. Landau DA, Tausch E, Taylor-Weiner AN, et al. Mutations driving CLL and their evolution in progression and relapse. Nature. 2015;526:525-530.
    1. The International CLL-IPI Working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016;17:779-790.

Publication types

Substances