S. Bea et al., BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas, CANCER RES, 61(6), 2001, pp. 2409-2412
The BMI-1 gene Is a putative oncogene belonging to the Polycomb group famil
y 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 tran
scriptional repressor of the INK4a/ARF locus. The BIMI-1 gene has been loca
ted on chromosome 10p13, a region involved in chromosomal translocations in
infant leukemias, and amplified in occasional non-Hodgkin's lymphomas (NHL
s) 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
BIMI-1 gene amplification (3- to 7-fold) in 4 of 36 (11%) mantle cell lymp
homas (MCLs) with no alterations in the INK4a/ARF locus. BMI-1 and p16(INK4
a) mRNA and protein expression were also studied by real-time quantitative
reverse transcription-PCR and Western blot, respectively, in a subset of NH
Ls, BMI-1 expression was significantly higher in chronic lymphocytic leukem
ia 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-I gene in germline configuration. Five ad
ditional MCLs also showed very high mRNA levels without gene amplification.
A good correlation between BMI-1 mRNA levels and protein expression was ob
served in all types of lymphomas, No relationship was detected between BMI-
1 and p16(INK4a) mRNA levels. These findings suggest that BMI-1 gene altera
tions in human neoplasms are uncommon, but they may contribute to the patho
genesis in a subset of malignant lymphomas, particularly of mantle cell typ
e.