title: Incomplete DJH rearrangements of the IgH gene are frequent in multiple myeloma patients: immunobiological characteristics and clinical implications.
abstract: DH-JH rearrangements of the Ig heavy-chain gene (IGH) occur early during B-cell development. Consequently, they are detected in precursor-B-cell acute lymphoblastic leukemias both at diagnosis and relapse. Incomplete DJH rearrangements have also been occasionally reported in mature B-cell lymphoproliferative disorders, but their frequency and immunobiological characteristics have not been studied in detail. We have investigated the frequency and characteristics of incomplete DJH as well as complete VDJH rearrangements in a series of 84 untreated multiple myeloma (MM) patients. The overall detection rate of clonality by amplifying VDJH and DJH rearrangements using family-specific primers was 94%. Interestingly, we found a high frequency (60%) of DJH rearrangements in this group. As expected from an immunological point of view, the vast majority of DJH rearrangements (88%) were unmutated. To the best of our knowledge, this is the first systematic study describing the incidence of incomplete DJH rearrangements in a series of unselected MM patients. These results strongly support the use of DJH rearrangements as PCR targets for clonality studies and, particularly, for quantification of minimal residual disease by real-time quantitative PCR using consensus JH probes in MM patients. The finding of hypermutation in a small proportion of incomplete DJH rearrangements (six out of 50) suggests important biological implications concerning the process of somatic hypermutation. Moreover, our data offer a new insight in the regulatory development model of IGH rearrangements.
authors.affiliation: 1Hematology Department, University Hospital of Salamanca, Paseo San Vicente, Salamanca, Spain.
authors.forename: D
authors.initials: D
authors.lastname: González
authors.forename: A
authors.initials: A
authors.lastname: Balanzategui
authors.forename: R
authors.initials: R
authors.lastname: García-Sanz
authors.forename: N
authors.initials: N
authors.lastname: Gutiérrez
authors.forename: C
authors.initials: C
authors.lastname: Seabra
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: M
authors.initials: M
authors.lastname: González
authors.forename: J F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D002999:Clone Cells; D005092:Exonucleases / Q000378:metabolism; D005787:Gene Frequency; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D015994:Incidence; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D017422:Sequence Analysis, DNA; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D005092:Exonucleases