Use of VH, D and JH immunoglobulin gene segments in Brazilian patients with Chronic lymphocytic Leukaemia (CLL)

Abstract

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy for which reliable prognostic markers are needed in view of its clinical heterogeneity. In approximately 50% of CLL patients, immunoglobulin (Ig) rearrangements are modified by somatic hypermutation (SHM), a process that represents a reliable prognostic indicator of favourable progression. In this study, we investigated SHM in 37 Brazilian CLL patients and identified the preferential involvement of specific immunoglobulin gene families and segments through PCR-amplified fragments or subcloned fragments. Forty-one rearrangements were observed and 37 of them were functional. A 98% homology cut-off with germinal sequences showed 18 patients (48.7%) with SHM. Unmutated cases showed a poorer clinical outcome. VH3 was the most frequent VH family, followed by VH4. The VH4-39 segment was the most frequently used, mainly in unmutated cases, while the VH3 family was predominant in mutated cases. The D3 and JH4/JH6 families were the most frequently observed. Copyright © 2008, Sociedade Brasileira de Genética.