A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by...

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Chronic lymphocytic leukemia (CLL) is a common B-cell neoplasm in Western countries, primarily affecting elderly individuals.
• CLL exhibits heterogeneous clinical courses, ranging from indolent to aggressive forms, with autoimmune complications like autoimmune hemolytic anemia (AIHA) being frequent.
• The precise mechanisms underlying autoimmune complications in CLL remain incompletely understood.

Observation:

• A 74-year-old male presented with severe macrocytic anemia and profound asthenia, indicative of active disease.
• Blood examination revealed a high White Blood Cell count and AIHA in the context of CLL.
• Genetic investigations identified trisomy 8, an unbalanced translocation involving chromosomes 6 and 11, and interstitial deletions on 6q and 11q.

Findings:

• Molecular cytogenetics confirmed monoallelic deletion of the Ataxia Telangiectasia Mutated (ATM) gene.
• Array-CGH refined the complex karyotype, detailing genomic losses on chromosomes 6 and 11.
• TP53 and IGHV mutations were absent, despite the presence of adverse genetic markers.

Implications:

• This case highlights an unusual CLL presentation with a complex karyotype and abrupt onset.
• Advanced genomic techniques like Array-CGH are crucial for comprehensive cytogenetic stratification beyond standard FISH analysis.
• Understanding these complex genetic profiles is essential for accurate prognostication and tailored treatment strategies in CLL.