IMMUNOGLOBULIN HEAVY CHAIN GENE REARRANGEMENTS IN B-CHRONIC LYMPHOPROLIFERATIVE DISORDERS

Many malignancies of mature B cells are characterized by chromosomal translocations involving the immunoglobulin heavy chain (IgH) locus on chromosome 14q32 and result in deregulated expression of the translocated oncogene. This work aimed to assess the presence of IgH gene rearrangement in B-chronic lymphoproliferative disorders (CLD) patients. The study was conducted on 30 patients suffrom B-CLDs selected from Ain Shams University Hospital, 18 males and 12 females (male: female ratio 1.5:1) with age ranging from 20-71 years (mean of 49+14 years). They were all subjected to complete blood count (CBC), bone marrow (BM) examination, immunophenotyping, histopatholog-ical examination of paraffin-embedded sections, conventional karyotyping by G-banding and FISH technique using fluorophore-labeled break apart DNA probe to hybridize to rearranged chromosome 14q32. Patients were followed up for the clinical outcome of the disease. Immunophenotypically, pa-tients were classified into 7 chronic lymphocytic leukemia (CLL) cases and 23 B-non Hodgkin s lym-phoma (NHL) cases, which were further subdivided histopathologically into 14 diffuse large B-cell lymphoma (DLBCL) cases, 6 follicular lymphoma (FL) and 3 mantle cell lymphoma (MCL) cases. Suc-cessful karyotyping was obtained in 22 cases. IgH rearrangement by FISH was positive in 12 cases, of which 5 only exhibited alternative abnormalities of chromosome 14 by G-banding. Only 1 case was CLL, while the remaining 11 were B-NHL cases. IgH gene rearrangement did not correlate with any of the studied parameters except histopathological grading of B-NHL. Furthermore, IgH gene re-arrangement was related to unfavorable clinical outcome. Therefore, FISH analysis is both sensitive and specific in detecting minor aberrations affecting IgH gene (14q32) in both metaphase and inter phase cells. Moreover IgH gene rearrangement (14q32) can be used as a marker of poorer clinical outcome in NHL cases.