TY - JOUR
T1 - Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC
AU - Nahar, Rahul
AU - Ramezani-Rad, Parham
AU - Mossner, Maximilian
AU - Duy, Cihangir
AU - Cerchietti, Leandro
AU - Geng, Huimin
AU - Dovat, Sinisa
AU - Jumaa, Hassan
AU - Ye, B. Hilda
AU - Melnick, Ari
AU - Müschen, Markus
PY - 2011/10/13
Y1 - 2011/10/13
N2 - Initial cell surface expression of the pre-B cell receptor induces proliferation. After 2 to 5 divisions, however, large pre-BII (Fraction C′) cells exit cell cycle to become resting, small pre-BII cells (Fraction D). The mechanism by which pre-BII cells exit cell cycle, however, is currently unclear. The checkpoint at the Fraction C′-D transition is critical for immunoglobulin light chain gene recombination and to prevent malignant transformation into acute lymphoblastic leukemia. Here we demonstrate that inducible activation of pre-B cell receptor signaling induces cell-cycle exit through upregulation of the transcriptional repressor BCL6. Inducible activation of BCL6 downstream of the pre-B cell receptor results in transcriptional repression of MYC and CCND2. Hence, pre-B cell receptor-mediated activation of BCL6 limits pre-B cell proliferation and induces cellular quiescence at the small pre-BII (Fraction D) stage.
AB - Initial cell surface expression of the pre-B cell receptor induces proliferation. After 2 to 5 divisions, however, large pre-BII (Fraction C′) cells exit cell cycle to become resting, small pre-BII cells (Fraction D). The mechanism by which pre-BII cells exit cell cycle, however, is currently unclear. The checkpoint at the Fraction C′-D transition is critical for immunoglobulin light chain gene recombination and to prevent malignant transformation into acute lymphoblastic leukemia. Here we demonstrate that inducible activation of pre-B cell receptor signaling induces cell-cycle exit through upregulation of the transcriptional repressor BCL6. Inducible activation of BCL6 downstream of the pre-B cell receptor results in transcriptional repression of MYC and CCND2. Hence, pre-B cell receptor-mediated activation of BCL6 limits pre-B cell proliferation and induces cellular quiescence at the small pre-BII (Fraction D) stage.
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UR - http://www.scopus.com/inward/citedby.url?scp=80054093403&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-01-331181
DO - 10.1182/blood-2011-01-331181
M3 - Article
C2 - 21856866
AN - SCOPUS:80054093403
SN - 0006-4971
VL - 118
SP - 4174
EP - 4178
JO - Blood
JF - Blood
IS - 15
ER -