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Precision Medicine Management of Chronic Lymphocytic Leukemia

Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Via Solaroli 17, 28100 Novara, Italy
Author to whom correspondence should be addressed.
Cancers 2020, 12(3), 642;
Received: 20 February 2020 / Revised: 6 March 2020 / Accepted: 8 March 2020 / Published: 10 March 2020
(This article belongs to the Special Issue Recent Advances in the Pathogenesis of B Cell Malignancies)
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in western countries, with an incidence of approximately 5.1/100,000 new cases per year. Some patients may never require treatment, whereas others relapse early after front line therapeutic approaches. Recent whole genome and whole exome sequencing studies have allowed a better understanding of CLL pathogenesis and the identification of genetic lesions with potential clinical relevance. Consistently, precision medicine plays a pivotal role in the treatment algorithm of CLL, since the integration of molecular biomarkers with the clinical features of the disease may guide treatment choices. Most CLL patients present at the time of diagnosis with an early stage disease and are managed with a watch and wait strategy. For CLL patients requiring therapy, the CLL treatment armamentarium includes both chemoimmunotherapy strategies and biological drugs. The efficacy of these treatment strategies relies upon specific molecular features of the disease. TP53 disruption (including both TP53 mutation and 17p deletion) is the strongest predictor of chemo-refractoriness, and the assessment of TP53 status is the first and most important decisional node in the first line treatment algorithm. The presence of TP53 disruption mandates treatment with biological drugs that inhibit the B cell receptor or, alternatively, the B-cell lymphoma 2 (BCL2) pathway and can, at least in part, circumvent the chemorefractoriness of TP53-disrupted patients. Beside TP53 disruption, the mutational status of immunoglobulin heavy variable (IGHV) genes also helps clinicians to improve treatment tailoring. In fact, patients carrying mutated IGHV genes in the absence of TP53 disruption experience a long-lasting and durable response to chemoimmunotherapy after fludarabine, cyclophosphamide, and rituximab (FCR) treatment with a survival superimposable to that of a matched general population. In contrast, patients with unmutated IGHV genes respond poorly to chemoimmunotherapy and deserve treatment with B cell receptor inhibitors. Minimal residual disease is also emerging as a relevant biomarker with potential clinical implications. Overall, precision medicine is now a mainstay in the management and treatment stratification of CLL. The identification of novel predictive biomarkers will allow further improvements in the treatment tailoring of this leukemia. View Full-Text
Keywords: chronic lymphocytic leukemia; target therapy; precision medicine chronic lymphocytic leukemia; target therapy; precision medicine
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MDPI and ACS Style

Moia, R.; Patriarca, A.; Schipani, M.; Ferri, V.; Favini, C.; Sagiraju, S.; Al Essa, W.; Gaidano, G. Precision Medicine Management of Chronic Lymphocytic Leukemia. Cancers 2020, 12, 642.

AMA Style

Moia R, Patriarca A, Schipani M, Ferri V, Favini C, Sagiraju S, Al Essa W, Gaidano G. Precision Medicine Management of Chronic Lymphocytic Leukemia. Cancers. 2020; 12(3):642.

Chicago/Turabian Style

Moia, Riccardo, Andrea Patriarca, Mattia Schipani, Valentina Ferri, Chiara Favini, Sruthi Sagiraju, Wael Al Essa, and Gianluca Gaidano. 2020. "Precision Medicine Management of Chronic Lymphocytic Leukemia" Cancers 12, no. 3: 642.

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