B-CELL NON-HODGKINS-LYMPHOMA - EVIDENCE FOR THE T(14, 18) TRANSLOCATION IN ALL HEMATOPOIETIC-CELL LINEAGES

Background: B cells of patients with non-Hodgkin's lymphoma (B-NHL) ha rbor specific chromosomal translocations, including t(14;18), the most common aberration found in this disease, The translocation involves t he immunoglobulin (Ig) heavy-chain joining (JH) region gene on chromos ome 14 and the BCL2 gene on chromosome 18, resulting in dysregulated e xpression of the BCL2 gene, The t(14;18) translocation has been though t to occur in the pre-B-cell stage, during the first event of Ig gene rearrangement, Purpose: This study was conducted to investigate the po tential involvement of nonlymphoid lineages in B-NHL. Methods: We stud ied the t(14;18) translocation and other frequently occurring transloc ations in total bone marrow aspirates of 10 patients with B-NHL, with the use of the fluorescence in situ hybridization (FISH) technique, We also performed cytogenetic analyses on representative bone marrow asp irates from the patients, Moreover, to define which of the major cell lineages present in the bone marrow carry the t(14;18) translocation, we used a series of monoclonal antibodies together with fluorescence-a ctivated cell sorter (FAGS) analyses to purify cells positive for CD3 (T cells), CD19 (B cells), CD10 (CALLA-positive cells), CD41a (megakar yocytic cells), CD13 (myeloid cells), and glycophorin A (erythroid cel ls), The cells of each subgroup underwent FISH analysis with the use o f JH and BCL2 probes to detect the t(14;18) translocation, Bone marrow samples obtained from five healthy donors served as controls, Results : Bone marrow cells from eight of the 10 patients studied carried the t(14;18) translocation, When present, the translocation was observed i n many or even all of the cell lineages (lymphoid, myeloid, megakaryoc ytic, and erythroid) present in the bone marrow, including peripheral blood progenitor stem cells; for seven of the eight patients carrying the translocation, it was found in 96%-100% of the unfractionated bone marrow cells as well as in all of the FAGS-purified cell fractions in which it could be detected or studied, Conventional cytogenetic analy ses performed on representative bone marrow aspirates confirmed the re sults obtained by FISH analysis, Cells in control bone marrow samples obtained from the five healthy donors were negative for the t(14;18) t ranslocation by FISH analysis, Conclusions: Our findings indicate that the t(14;18) translocation most probably occurs in a very early multi lineage progenitor stem cell, Implications: Given that the t(14;18) ch romosomal translocation was found in all types of bone marrow cells wh en only the B cells were malignant, our results suggest that this tran slocation is not sufficient to induce neoplastic transformation, This finding underscores the need for the development of new approaches for the detection and surveillance of B-NHL.