Nonrandom rearrangement of chromosome 14 at band q32.33 in human lymphoid malignancies with mature B-cell phenotype

Abstract

Chromosomes were studied in 61 patients with differentiated B-cell malignancies including 21 with non-Hodgkin's lymphoma (NHL), three with hairy cell leukemia (HCL), eight with Waldenström's macroglobulinemia (WM), and 29 with plasma cell disorder. Chromosomally abnormal clones were identified in 35 of 61 patients studied: all with NHL, all with HCL, three of eight with WM, and eight of 29 with plasma cell disorder. The most recurrent chromosomal abnormality, observed in 26 of the 35 patients whose chromosomes were abnormal, was a rearrangement involving chromosome 14, in which an additional segment was attached at band 32 in the long arm to form a 14q+ marker chromosome. This rearrangement was seen in 17 patients with NHL, three with HCL, one with WM, and five with plasma cell disorder. In NHL, the rearrangement correlates with histological subclasses: t(14;18) in all four patients with malignant lymphoma (ML)-follicular, mixed small cleaved and large cell; t(8;14) or its variant form, t(8;22), in all six with ML-small noncleaved cell; and t(11;14) in two of three with ML-diffuse, mixed small and large cell. A t(14;18) was also found in each patient with ML-diffuse, large cell, WM, and multiple myeloma, and a variant three-way translocation, t(5;18;14) (q13;q21;q32), in one with ML-diffuse, small cleaved cell. The donor sites for these 14q+ were assigned to oncogene loci: c-myc (8q24), bcl-1 (11q13), and bcl-2 (18q21). Moreover, the donor sites were also located near immunoglobulin light chain gene loci in each patient with leukemic ML-diffuse, mixed small and large cell, t(2;14) (p13;q32.3), and HCL, t(14;22)(q32.3;q11.2). These findings suggest that chimeric DNA formation, not only between an immunoglobulin gene and a certain oncogene, but also between the IgH gene and one of the IgL genes may be potentially relevant in malignant B-cell proliferation.