Chronic Lymphocytic Leukemia Coverage from Every Angle

Putting Clonal Evolution to Practical Use in Chronic Lymphocytic Leukemia

By: Celeste L. Dixon
Posted: Monday, October 21, 2019

Integrating genetic, epigenetic, and transcriptional information more frequently than is already done in the clinical management of patients with chronic lymphocytic leukemia (CLL) is crucial to tailor targeted treatments in an optimized, synergic manner. Backed by an abundance of evidence, coauthors Adalgisa Condoluci, MD, and Davide Rossi, MD, both of the Oncology Institute of Southern Switzerland in Bellinzona, made their contention at the 2019 Society of Hematologic Oncology Annual Meeting in Houston (Abstract EXABS-CLL-413). Their presentation also was published in Clinical Lymphoma, Myeloma & Leukemia.

The predictive and prognostic values of some CLL biomarkers are incontrovertible, noted the authors. The “burden” of the genetic information and characteristics that technology can provide must be utilized to “follow clonal evolution and possibly avoid clonal selection conferring disease refractoriness.”

CLL develops slowly, making it “a highly informative model of clonal heterogeneity and dynamics during cancer progression, response to therapy, and/or relapse,” summarized Drs. Condoluci and Rossi. “The typical genome of unselected CLL harbors ∼2,000 molecular lesions, with few mutations recurring at a frequency > 5% and a large number of biologically and clinically uncharacterized genes mutated at lower frequencies. These mutations identify a variety of clones and subclones, which will evolve differently, according to intrinsic (microenvironment) and extrinsic (therapy) pressures.”

One of the best-known upregulated genes in CLL is BCL2, which occurs as a consequence of miR15A/miR16A deletion and is a therapeutic target of venetoclax. More recent genomic studies with next-generation sequencing have revealed recurrent mutations that affect genes “that can be clustered in a small set of pathways,” explained the authors. These pathways include microenvironment-dependent signaling, inflammatory receptors, MAPK-ERK and NF-κB pathways, intracellular programs such as DNA-damage and cell-cycle control, chromatin modification, transcription, and ribosomal processing.

Disclosure: The study authors’ disclosure information can be found at

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