Distinct chromosome 3 abnormalities in persistent polyclonal B-cell lymphocytosis

Area of Science:

• Hematology
• Cytogenetics
• Oncology

Background:

• Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare B-lymphocyte disorder of unknown cause.
• It is characterized by polyclonal B-cell expansion, elevated IgM, and a specific chromosomal abnormality: isochromosome 3q.
• Previous understanding identified only the isochromosome 3q (+i(3)(q10)) as the sole cytogenetic change.

Purpose of the Study:

• To investigate the cytogenetic landscape of PPBL beyond the established isochromosome 3q.
• To determine if other chromosomal abnormalities are consistently present in PPBL cases.
• To elucidate the distribution of chromosomal abnormalities within the B-lymphocyte population in PPBL.

Main Methods:

• Conventional cytogenetic analysis and Fluorescence In Situ Hybridization (FISH) were performed on four PPBL cases.
• Immunophenotypic studies confirmed B-lymphocyte polyclonality.
• Polymerase Chain Reaction (PCR) assessed immunoglobulin heavy chain (IGH) rearrangements.
• Simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION) was used to analyze chromosomal abnormality distribution.

Main Results:

• All four PPBL cases exhibited the characteristic +i(3)(q10).
• Two patients also showed unrelated clones with trisomy 3 (+3) via banding techniques.
• FISH confirmed the presence of both +i(3)(q10) and +3 in all evaluated cases.
• FICTION analysis demonstrated that both chromosomal abnormalities were randomly distributed among B-lymphocytes.

Conclusions:

• Trisomy 3 (+3) is identified as a recurrent cytogenetic abnormality in PPBL, in addition to +i(3)(q10).
• These findings suggest an increased frequency of chromosome 3 instability in PPBL.
• The random distribution of these abnormalities implies a potential early event in the pathogenesis of this lymphoproliferative disorder.