A Plasma Cell Leukemia Patient Showing Bialleic 14q Translocations: t(2;14) and t(11;14)

Abstract

We report here an IgG/λ-type plasma cell leukemia patient showing bialleic 14q32 translocations. All immunoglobulins were suppressed in this patient, but a small amount of monoclonal IgG was detected by immunoelectrophoresis. Two cells of six peripheral blood mononuclear cells showed 46,XY,t(2;14)(q11;q32), i(8)(q10), t(11;14)(q13;q32), del(12)(q13.1) by karyotypic analysis. We confirmed the juxtaposition of IgH and PRAD1/Cyclin D1 genes by fluorescent in situ hybridization and overexpression of the PRAD1/Cyclin D1 gene, but Southern analysis showed no bcl-1 rearrangement. We analyzed the t(2;14)(q11;q32) using DNA fragments derived from childhood B-chronic lymphocytic leukemia cases bearing t(2;14)(p13;q32). Southern and Northern analyses demonstrated no alteration of these genes, indicating that this t(2;14) was different from that of childhood B-chronic lymphocytic leukemia. At the IgH loci, Southern analysis showed two rearranged bands and one germ-line band of JH. Cμ was deleted on one rearranged allele but remained on the other, suggesting that the chromosome translocation occurred after productive class switch recombination on the Cμ deleted allele.

POU2AF1, an amplification target at 11q23, promotes growth of multiple myeloma cells by directly regulating expression of a B-cell maturation factor, TNFRSF17

“…Gains of 11q in plasma cells have been reported in 20-45% of MM patients, ranging from trisomies to single chromosomal bands (Cigudosa et al, 1998;Gutierrez et al, 2001). Aberration of 11q13 is probably due to cyclin D1, which is overexpressed as a result of translocation or an amplification mechanism (Sonoki et al, 1998;Hoechtlen-Vollmar et al, 2000). The targets in other affected regions of 11q, such as 11q23 and 11q25 (Gonzalez et al, 2004;Carrasco et al, 2006), remain unknown.…”

The BCL11 gene family: involvement of BCL11A in lymphoid malignancies

“…1,[3][4][5][6] Chromosomal translocation t(2;14) (p13;q32.3) is one example and has been reported in a variety of B-cell malignancies ranging from B-cell precursor acute lymphoblastic leukemia to myeloma. This translocation is frequently the sole cytogenetic abnormality within the neoplastic clone (Watson et al, 7 Geisler et al, 8 Sonoki et al, 9 and http://cgap.nci.nih.gov/ Chromosomes/Mitelman). We report here the recurrent involvement and deregulated expression of a Krüppel zinc finger gene, BCL11A, in 4 cases of B-cell malignancy with t(2;14)(p13;q32.3).…”

Molecular features responsible for the absence of immunoglobulin heavy chain protein synthesis in an IgH− subgroup of multiple myeloma

“…5 Even biallelic translocations involving IGH genes may be accompanied by a normal IgH ϩ phenotype. 8,45 Nevertheless, our data clearly show that in at least 2 (but probably 3) of our patients an illegitimate class switch rearrangement seems to be the sole cause of the absence of IgH proteins, whereas in additional 2 cases, it appeared to be one of the causes for IgH negativity (Table 3).…”