The Heterogeneity of 13q Deletions in Chronic Lymphocytic Leukemia: Diagnostic Challenges and Clinical Implications

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, particularly in Western countries. CLL can present indolently or aggressively, influenced by various factors, including chromosomal alterations. Fluorescent in situ hybridization (FISH), targeting specific genes/loci frequently affected in CLL patients, has established a standard for stratifying five CLL prognostic groups: del(11q)/ATM, trisomy 12, del(13q) as a sole aberration, del(17p)/TP53, and normal CLL FISH panel results. Among these, del(13q) as a sole aberration is associated with a favorable prognosis, while the others are considered intermediate (normal CLL FISH panel result and trisomy 12) or unfavorable (del(11q)/ATM and del(17p)/TP53) prognostic markers. However, significant heterogeneity in del(13q) aberrations has been observed among CLL patients with isolated del(13q), which should be considered when predicting prognosis and planning clinical management for individual CLL patients with this aberration. This review discusses the variations in del(13q) aberrations in CLL, including a minimally deleted region (MDR), the anatomic sizes of deleted 13q regions, affected alleles, the clone sizes of del(13q), and their dynamic changes during disease progression. The impact of del(13q) heterogeneity on various diagnostic tests such as karyotyping, the FISH panel, chromosomal microarray (CMA), and optical genome mapping (OGM), prognostic prediction, and clinical management is illustrated through authentic clinical scenarios.