Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias.
The t(11;14)(q13;q32) translocation and its molecular counterpart, BCL-1 rearrangement, are consistent features of intermediate lymphocytic lymphoma (ILL). Rearrangement is thought to deregulate the nearby PRAD-1/BCL-1 proto-oncogene that is a newly identified member of the cyclin family. To characterize further the association between rearrangement of chromosome 11q13 and over-expression of BCL-1. Southern blot analysis was performed in 33 cases of ILL, 5 cases of t(11;14)-associated leukemias, and 1 case of leukemia carrying a variant translocation t(11;19)(q13;q13) using three separate BCL-1 locus probes. When RNA was available, BCL-1 expression was assessed by Northern blot analysis. DNA from 19 of 33 ILL (57%) showed BCL-1 rearrangement, 16 involving the major translocation cluster (MTC) region and 3 involving a new breakpoint cluster located in the 5' flanking region of the BCL-1 gene. DNA from 3 of 6 t(11q13)-associated leukemias demonstrated a rearrangement involving the MTC. Northern blot analysis showed that BCL-1 was overexpressed in 14 of 15 ILL and in all leukemias analyzed (included the t(11;19) leukemia) relative to normal and malignant lymphoid tissues. These results constitute additional elements in favor of the role of BCL-1 in lymphoid neoplasia and allow us to speculate about its mechanisms of activation.
Laboratoire de Cytogénétique Moléculaire, Hôpital Edouard Herriot, Lyon, France.
R
R
Rimokh
F
F
Berger
G
G
Delsol
C
C
Charrin
M F
MF
Berthéas
M
M
Ffrench
M
M
Garoscio
P
P
Felman
B
B
Coiffier
P A
PA
Bryon
D000368:Aged; D002880:Chromosomes, Human, Pair 11; D019938:Cyclin D1; D005260:Female; D015870:Gene Expression; D015321:Gene Rearrangement; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014178:Translocation, Genetic
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019938:Cyclin D1