PMID- 21631271
OWN - NLM
STAT- MEDLINE
DCOM- 20110809
LR  - 20211203
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
VI  - 135
IP  - 6
DP  - 2011 Jun
TI  - Uniform expression of Notch1, suppressor of B-cell-specific gene expression, in 
      plasmablastic lymphoma.
PG  - 770-5
AB  - CONTEXT: Although the loss of B-lineage-specific gene expression is a distinctive 
      feature of plasmablastic lymphoma, the underlying mechanism remains poorly 
      understood. A candidate for this mechanism is Notch1 signaling, which interferes 
      with the activity of B-cell-specific transcription factors E2A and early B-cell 
      factor and positively regulates the mammalian target of rapamycin (mTOR) pathway. 
      OBJECTIVE: To explore the mechanism of loss of B-cell phenotype by correlating 
      expression of B-cell markers with that of Notch1 and downstream targets of the 
      mTOR pathway in plasmablastic lymphoma. DESIGN: A combination of flow cytometric 
      and immunohistochemical immunophenotyping techniques was used on 9 cases of 
      plasmablastic lymphoma to correlate loss of B-cell markers with expression of 
      Notch1 and downstream activation of the mTOR pathway. These results are compared 
      with 5 cases of primary effusion lymphoma and 21 cases of plasma cell myeloma. 
      RESULTS: Plasmablastic lymphoma cases exhibit nearly complete loss of 
      B-cell-associated markers and uniform expression of Notch1, with a predominantly 
      nuclear staining pattern. There is a concurrent activation of the mTOR pathway, 
      indicated by expression of mTOR targets eukaryotic initiation factor 4E-binding 
      protein 1 and phosphorylated ribosomal protein S6 in most cases. Similar results 
      are seen in cases of primary effusion lymphoma and plasma cell myeloma. 
      CONCLUSIONS: These findings suggest that activation of Notch1 may be involved in 
      suppression of B-cell-specific gene expression and global loss of the B-cell 
      phenotype in plasmablastic lymphoma, similar to primary effusion lymphoma and 
      plasma cell myeloma. Thus, there might be a role for the Notch1 and mTOR pathways 
      in the pathogenesis and therapy of plasmablastic lymphoma.
FAU - Seegmiller, Adam C
AU  - Seegmiller AC
AD  - Department of Pathology, University of Texas Southwestern Medical Center at 
      Dallas, USA.
FAU - Wang, Huan-You
AU  - Wang HY
FAU - Hladik, Christa
AU  - Hladik C
FAU - Chen, Weina
AU  - Chen W
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Lymphokines)
RN  - 0 (NOTCH1 protein, human)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptor, Notch1)
RN  - 0 (TCF3 protein, human)
RN  - 0 (suppressive B cell factor)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Adult
MH  - Anti-HIV Agents/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Antiretroviral Therapy, Highly Active/methods
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Biomarkers, Tumor/*metabolism
MH  - Cell Cycle Proteins
MH  - Female
MH  - Flow Cytometry
MH  - HIV Seropositivity
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunophenotyping
MH  - Lymphokines/*genetics
MH  - Lymphoma, Large-Cell, Immunoblastic/drug therapy/*metabolism/pathology
MH  - Lymphoma, Primary Effusion/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/metabolism/pathology
MH  - Phosphoproteins/metabolism
MH  - Plasma Cells/*pathology
MH  - Receptor, Notch1/*metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2011/06/03 06:00
MHDA- 2011/08/10 06:00
CRDT- 2011/06/03 06:00
PHST- 2011/06/03 06:00 [entrez]
PHST- 2011/06/03 06:00 [pubmed]
PHST- 2011/08/10 06:00 [medline]
AID - 10.1043/2009-0691-OA.1 [pii]
AID - 10.5858/2009-0691-OA.1 [doi]
PST - ppublish
SO  - Arch Pathol Lab Med. 2011 Jun;135(6):770-5. doi: 10.5858/2009-0691-OA.1.