VH3–48 and VH3–53, as well as VH3–21, gene rearrangements define unique subgroups in CLL and are associated with biased lambda light chain restriction, homologous LCDR3 sequences and poor prognosis

This study determined IgVH gene usage in 228 chronic lymphocytic leukaemia patients to investigate associations between gene usage and other biological or clinical characteristics. VH3–48 [N = 8] and VH3–53 [N = 4] gene rearrangements showed biased λ light chain restriction and were predominantly found in female patients with short lymphocyte doubling time but without adverse prognosis cytogenetics. Overuse of VL3–21(Vλ2–14) gene and highly homologous LCDR3 sequences were found in VH3–48 patients. VH3–21 gene usage [N = 18, 7.9%] was associated with poor prognosis, overuse of VL3–21(Vλ2–14) gene and highly homologous heavy- and light-chain CDR3 sequences, but was not associated with poor prognosis chromosomal aberrations.