The BCL11 gene family: involvement of BCL11A in lymphoid malignancies

Many malignancies of mature B cells are characterized by chromosomal transl ocations. involving the immunoglobulin heavy chain (IGH) locus on chromosom e 14q32.3 and result in deregulated expression of the translocated oncogene . t(2;14)(p13; q32.3) is a rare event in B-cell malignancies. in contrast, gains and amplifications of the same region of chromosome 2p13 have been re ported in 20% of extranodal B-cell non-Hodgkin lymphomas (B-NHL), in follic ular and mediastinal B-NHL, and in Hodgkin disease (HID). It has been sugge sted that REL, an NF-kappaB gene family member, mapping within the amplifie d region, is the pathologic target. However, by molecular cloning of t(2;14 )(p13;q32.3) from 3 cases of aggressive B-cell chronic lymphocytic leukemia (CLL)/immunocytoma, this study has shown clustered breakpoints. an chromos ome 2p13 immediately upstream of a CpG island located about 300 kb telomeri c of REL. This CpG island was associated with a Kruppel zinc finger gene (B CL11A), which is normally expressed at high levels only in fetal brain and in germinal center B-cells. There were 3 major RNA isoforms of BCL11A, diff ering in the number of carboxy-terminal zinc fingers. All 3 RNA isoforms we re deregulated as a consequence of t(2;14) (p13;q32.3). BCL11A was highly c onserved, being 95% identical to mouse, chicken, and Xenopus homologues. BC L11A was also highly homologous to another gene (BCL11B) on chromosome 14q3 2.1. BCL11A coamplified with REL in B-NHL cases and HID lymphoma cell lines with gains and amplifications of 2p13, suggesting that BCL11A may be invol ved in lymphoid malignancies through either chromosomal translocation or am plification. (Blood. 2001;98:3413-3420) (C) 2001 by The American Society of Hematology.