Chronic Lymphoid Leukemia: CEITEC scientists recommend a proficient diagnostic approach

61000 - this is the number of annual deaths caused globally by Chronic Lymphoid Leukemia (CLL) 1

By the time, you finish the article; roughly, 4 people will come within the grasp of this disease. 


  Death (Credit: Photo by Anthony DELANOIX on Unsplash)

CLL is an incurable form of blood cancer, affecting the lymphocytes, a subtype of the white blood cells – the warriors against microorganisms or other harmful agents.

The precise reasons behind CLL are not recognized yet

Numerous genetic mutations occur in the DNA of the blood-cell-generating cells in the bone marrow, and consequently, abnormal lymphocytes are produced. Once the abnormal cells are accumulated and outnumber the regular lymphocytes, the person develops CLL. Consistent with other cancers, in CLL too, the TP53 gene can be mutated.

The TP53 gene encodes for a tumor suppressor protein p53 which helps cells in our body to grow and divide in a controlled fashion. When p53 fails to do its task, cells proliferate frenziedly, triggering tumor-formation – a hallmark of cancer.

Approximately 50-75% of patients with chronic lymphocytic leukemia do not display any symptoms; thus, most of them do not need treatment.  

In contrast, there are patients with the progressive disease - requiring early therapeutic intervention.

But then, the most challenging group of patients are with the chemo-refractory state, who don’t respond to the standard chemo-immunotherapy. Many biomarkers (assessable indicators of the severity or presence of some disease condition) are available, which help physicians to recognize patients at risk of aggressive disease – mutation in the TP53 gene is the most vital element among them.

With the aim to have a streamlined and standardized diagnostic system, the European Research Initiative on CLL (ERIC) was established in 2001 

As an important part of ERIC, the TP53 network, coordinated by the CEITEC scientist Prof. Šárka Pospíšilová, aims to promote and furtherance of the assessment of TP53 gene abnormalities for diagnostic purposes.

The TP53 network has put forward an updated report 2 to recommend about the practical details of the diagnostic approach to detect TP53 gene mutations.

Dr. Jitka Malčíková, the lead author of this report, states, “patients with TP53 defects suffer from aggressive disease and are resistant to standard chemo-immunotherapy. Therefore, the TP53 gene is currently tested in all patients entering the treatment. This approach represents the standard of care in the majority of countries and is unique for CLL, as TP53 is not routinely tested in other diseases.”

She asserts that “there are several reasons why TP53 testing is well established just in CLL; mainly, the impact of TP53 defects on treatment outcome has been well documented in CLL patients in many clinical trials. In addition, long-term educational activities of ERIC has been playing an important role in the establishment of TP53 testing.”


Dr. Jitka Malčíková (Photography by Emil Gallík)

In order not to overlook any patient having TP53 mutation, the current ERIC recommendation is to sequence the entire coding region of the gene (the part which codes for the resultant protein), by means of conventional DNA sequencing techniques (Sanger sequencing and Next Generation Sequencing technologies).

This approach from ERIC to be not solely beneficial for the researchers, but supremely for the common people

Dr. Malčíková adds, "The operation of ERIC is ultimately valuable for chronic lymphocytic leukemia patients, as the main aim of this initiative is to improve the diagnostics and treatment of this incurable disease."

By stitching the CLL research community together, the TP53 network of ERIC has offered a platform where awareness, education, expertise, and help are provided to ease the process of detecting the TP53 defects.

Realizing the future, treating the patients resistant to chemo-immunotherapy, personalized precision medicine could be an avenue, and Dr. Malčíková thinks, “precision medicine could be applied to all patients and we won´t have to wait until the chemoresistance manifests.” 


Hope (Photo by Scott Eckersley on Unsplash)

She adds further, “apart from TP53, there are also mutations in other genes that contribute to chemo-resistant behavior of cancer cells. The tools for early detection of such mutations are already available and multiple new biological agents are under development. I hope in the future, the new drugs, or, more likely combination of drugs, could be used to directly target the particular cancer cell.” 

And we hope, her hopes become reality!


  1. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study.
  2. Malcikova J, Tausch E, Rossi D, Sutton LA, Soussi T, Zenz T, Kater AP, Niemann CU, Gonzalez D, Davi F, Gonzalez Diaz M, Moreno C, Gaidano G, Stamatopoulos K, Rosenquist R, Stilgenbauer S, Ghia P, Pospisilova S (2018) ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—update on methodological approaches and results interpretation. Leukemia 32(5):1070–1080

Written by Somsuvro Basu

Publication date: 29.03.2019