BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas

• Published in: Cancer research (Chicago, Ill.) Vol. 61; no. 6; pp. 2409 - 2412
• Main Authors: BEA, Silvia, TORT, Frederic, PINYOL, Magda, PUIG, Xavier, HERNANDEZ, Luis, HERNANDEZ, Silvia, FERNANDEZ, Pedro L, VAN LOHUIZEN, Maarten, COLOMER, Dolors, CAMPO, Elias
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-03-2001
• Subjects: Biological and medical sciences; BMI-1 gene; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Gene Amplification; Gene Expression; Genes, Tumor Suppressor; Hematologic and hematopoietic diseases; Hematologic Neoplasms - genetics; Hematologic Neoplasms - metabolism; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Mantle-Cell - genetics; Lymphoma, Mantle-Cell - metabolism; mantle cell lymphoma; Medical sciences; non-Hodgkin's lymphoma; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; p16INK4a protein; Polycomb Repressive Complex 1; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Repressor Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Human; Solid tumor; Carcinoma; Pathogenesis; Gene product; Tumoral tissue; Gene overexpression; Hodgkin disease; Malignant hemopathy; Large cell lymphoma; Gene expression; Lymphoma; Epidemiology; In vitro; CDKN2 gene; Gene amplification; Chronic lymphocytic leukemia; Lymphoproliferative syndrome; Chronic myelocytic leukemia; Mantle cell lymphoma; Onc gene
• ISSN: 0008-5472; 1538-7445

The BMI-1 gene is a putative oncogene belonging to the Polycomb group family that cooperates with c-myc in the generation of mouse lymphomas and seems to participate in cell cycle regulation and senescence by acting as a transcriptional repressor of the INK4a/ARF locus. The BMI-1 gene has been located on chromosome 10p13, a region involved in chromosomal translocations in infant leukemias, and amplified in occasional non-Hodgkin's lymphomas (NHLs) and solid tumors. To determine the possible alterations of this gene in human malignancies, we have examined 160 lymphoproliferative disorders, 13 myeloid leukemias, and 89 carcinomas by Southern blot analysis and detected BMI-1 gene amplification (3- to 7-fold) in 4 of 36 (11%) mantle cell lymphomas (MCLs) with no alterations in the INK4a/ARF locus. BMI-1 and p16INK4a mRNA and protein expression were also studied by real-time quantitative reverse transcription-PCR and Western blot, respectively, in a subset of NHLs. BMI-1 expression was significantly higher in chronic lymphocytic leukemia and MCL than in follicular lymphoma and large B cell lymphoma. The four tumors with gene amplification showed significantly higher mRNA levels than other MCLs and NHLs with the BMI-1 gene in germline configuration. Five additional MCLs also showed very high mRNA levels without gene amplification. A good correlation between BMI-1 mRNA levels and protein expression was observed in all types of lymphomas. No relationship was detected between BMI-1 and p16INK4a mRNA levels. These findings suggest that BMI-1 gene alterations in human neoplasms are uncommon, but they may contribute to the pathogenesis in a subset of malignant lymphomas, particularly of mantle cell type.