Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and represented 17.5% of all global leukemia cases in 2017.1 It mainly affects the elderly, with an average age at time of diagnosis of around 70. The clinical course of CLL is somewhat heterogeneous. As its name suggests, it is usually chronic and relatively indolent – even asymptomatic in some patients – but it can also become aggressive. Between 2% and 10% of patients with symptomatic CLL develop Richter's syndrome,2 where their condition transforms into a more aggressive lymphoma – usually diffuse large B cell lymphoma – carrying a much poorer prognosis.


The immunoglobulin (IG) molecules that form part of the B cell receptor (BCR) play a pivotal role in CLL pathogenesis, and contribute to disease initiation and progression. All CLLs are derived from mature, antigen-experienced B cells that may proceed down one of two cellular pathways after antigen exposure, giving rise to two distinct disease subsets. M-CLL originates from B cells that have undergone a T cell dependent reaction – leading to the generation of memory B cells with a somatic hypermutation of IG heavy chain variable region (IGHV) genes – while U-CLL arises from a T cell independent reaction that leads to the formation of B cells with unmutated IGHV genes.3 This is clinically relevant as U-CLLs are associated with a more aggressive disease, and carry a higher chance of undergoing clonal evolution.3 BCR interaction with the microenvironment is also associated with further CLL cell proliferation and apoptosis inhibition.2

Diagnosis and treatment assessment

Many patients – certainly asymptomatic ones – are diagnosed with CLL when routine blood tests show lymphocytosis. A firm diagnosis is based on the presence of ≥5 x 109/L monoclonal B cells in peripheral blood, sustained for at least three months.4 Clonality can be confirmed by using flow cytometry to demonstrate IG light chain restriction.4

Treatment options are vast and generally tailored to individual patients because of the diverse nature of the disease. Eradication is obviously preferable, but prolonged progression-free survival is also an acceptable goal.5 Minimal residual disease (MRD) monitoring, which describes the number of cancer cells remaining after treatment, is becoming increasingly popular to measure treatment success. Six color flow cytometry, PCR, or high throughput sequencing can be used to detect MRD, and all offer the required sensitivity of 10-4.4

Cell markers

Flow cytometry analysis comprises a core panel of six markers – CD19, CD20, CD5, CD43, CD79b, and CD81 – though new instruments can offer an eight or ten color analysis.6 Additional markers may include CD45, CD3, CD200, CD23, ROR1, or CD160.6

All Reagents from Beckman Coulter Life Sciences may not be available for clinical use and may be Research Use Only in certain jurisdictions. You can explore our Single Color Reagent portfolio by regulatory status, fluorochrome, isotype, format and more here.

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  1. Dong Y, Shi O et al. (2020) Leukemia incidence trends at the global, regional, and national level between 1990 and 2017. Exp Hematol Oncol. 9 (14).
  2. Delgado J, Nadeu F et al. (2020) Chronic lymphocytic leukemia: from molecular pathogenesis to novel therapeutic strategies. Haematologica.105(9):2205-2217. doi:10.3324/haematol.2019.236000
  3. Gaidano G, Foà R et al. (2012) Molecular pathogenesis of chronic lymphocytic leukemia. J Clin Invest. 122(10):3432-3438. doi:10.1172/JCI64101
  4. Hallek M, Cheson BD et at. (2018) iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 131 (25): 2745–2760. doi:
  5. Kovacs G, Robrecht S et al. (2016) Minimal Residual Disease Assessment Improves Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia (CLL) Who Achieve Partial Response: Comprehensive Analysis of Two Phase III Studies of the German CLL Study Group. J Clin Oncol. 34 (31): 3758-3765. DOI: 10.1200/JCO.2016.67.1305
  6. Rawstron AC, Fazi C et al. (2016) A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study. Leukemia. 30(4):929-936. doi:10.1038/leu.2015.313

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