PMID- 22039300
OWN - NLM
STAT- MEDLINE
DCOM- 20120113
LR  - 20111121
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 187
IP  - 11
DP  - 2011 Dec 1
TI  - A p53 defect sensitizes various stages of B cell development to lymphomagenesis 
      in mice carrying an IgH 3' regulatory region-driven c-myc transgene.
PG  - 5772-82
LID - 10.4049/jimmunol.1102059 [doi]
AB  - Although c-myc is classically described as the driving oncogene in Burkitt's 
      lymphoma (BL), deregulation and mutations of c-myc have been reported in multiple 
      solid tumors and in other mature B cell malignancies such as mantle cell lymphoma 
      (MCL), myeloma, and plasma cell lymphoma (PCL). After translocation into the IgH 
      locus, c-myc is constitutively expressed under the control of active IgH 
      enhancers. Those located in the IgH 3' regulatory region (3'RR) are master 
      control elements of class switch recombination and of the transcriptional burst 
      associated with plasma cell differentiation. c-myc-3'RR mice are prone to 
      lymphomas with rather homogeneous, most often BL-like, phenotypes with incomplete 
      penetrance (75% tumor incidence) and long latencies (10-12 mo). To reproduce 
      c-myc-induced mature B cell lymphomagenesis in the context of an additional 
      defect often observed in human lymphomas, we intercrossed c-myc-3'RR with 
      p53(+/-) mice. Double transgenic c-myc-3'RR/p53(+/-) mice developed lymphoma with 
      short latency (2-4 mo) and full penetrance (100% tumor incidence). The spectrum 
      of B lymphomas occurring in c-myc-3'RR/p53(+/-) mice was widened, including 
      nonactivated (CD43(-)) BL, activated (CD43(+)) BL, MCL-like lymphoma, and PCL, 
      thus showing that 3'RR-mediated deregulation of c-myc can promote various types 
      of B lymphoproliferation in cells that first acquired a p53 defect. 
      c-myc/p53(+/-) mice closely reproduce many features of BL, MCL, and PCL and 
      provide a novel and efficient model to dissect the molecular events leading to 
      c-myc-induced lymphomagenesis and an important tool to test potential therapeutic 
      agents on malignant B cells featuring various maturation stages.
FAU - Fiancette, Remi
AU  - Fiancette R
AD  - Faculte de Medecine, Unite Mixte de Recherche 6101, Centre National de la 
      Recherche Scientifique, 87025 Limoges, France.
FAU - Rouaud, Pauline
AU  - Rouaud P
FAU - Vincent-Fabert, Christelle
AU  - Vincent-Fabert C
FAU - Laffleur, Brice
AU  - Laffleur B
FAU - Magnone, Virginie
AU  - Magnone V
FAU - Cogne, Michel
AU  - Cogne M
FAU - Denizot, Yves
AU  - Denizot Y
LA  - eng
SI  - GEO/GSE31814
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111028
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/*pathology
MH  - Cell Separation
MH  - Cell Transformation, Neoplastic/*genetics/immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Genes, myc/*genetics
MH  - Immunoglobulin Heavy Chains/*genetics
MH  - Lymphoma/*genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Oligonucleotide Array Sequence Analysis
MH  - Regulatory Sequences, Nucleic Acid/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transgenes
MH  - Tumor Suppressor Protein p53/*genetics
EDAT- 2011/11/01 06:00
MHDA- 2012/01/14 06:00
CRDT- 2011/11/01 06:00
PHST- 2011/11/01 06:00 [entrez]
PHST- 2011/11/01 06:00 [pubmed]
PHST- 2012/01/14 06:00 [medline]
AID - jimmunol.1102059 [pii]
AID - 10.4049/jimmunol.1102059 [doi]
PST - ppublish
SO  - J Immunol. 2011 Dec 1;187(11):5772-82. doi: 10.4049/jimmunol.1102059. Epub 2011 
      Oct 28.