PMID- 19081173
OWN - NLM
STAT- MEDLINE
DCOM- 20090217
LR  - 20210102
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Linking)
VI  - 37
IP  - 2
DP  - 2009 Feb
TI  - Alterations in CIITA constitute a common mechanism accounting for downregulation 
      of MHC class II expression in diffuse large B-cell lymphoma (DLBCL).
PG  - 184-194
LID - 10.1016/j.exphem.2008.10.001 [doi]
AB  - OBJECTIVE: Significant decreases in patient survival are associated with 
      downregulation of major histocompatibility complex class II (MHC-II) antigen 
      expression in diffuse large B-cell lymphoma (DLBCL). However, the molecular 
      mechanisms responsible for decreased MHC-II expression in DLBCL are poorly 
      defined. We therefore examined these mechanisms in established DLBCL cell lines. 
      MATERIALS AND METHODS: Human leukocyte antigen (HLA)-DR surface expression was 
      examined by flow cytometry. Expression of the MHC-II genes and the MHC-II 
      transcriptional activators class II transactivator (CIITA) and RFX was 
      investigated by reverse transcriptase polymerase chain reaction. The integrity of 
      the MHC-II genes was examined by polymerase chain reaction. Stable transfection 
      assays were utilized to reconstitute CIITA expression. RESULTS: Dramatic 
      variations in the levels of cell surface HLA-DR expression were observed on the 
      DLBCL cell lines. OCI-Ly10 cells lack HLA-DR and HLA-DQ expression due to 
      homozygous deletions within the MHC-II locus on chromosome 6. Dyscoordinate 
      downregulation of MHC-II beta-chain expression in OCI-Ly3 cells mediates dramatic 
      reductions of MHC-II surface expression. In SUDHL-4 and SUDHL-6 cells, expression 
      of the MHC-II genes is coordinately reduced and quantitatively correlated with 
      expression of the CIITA, the master regulator of MHC-II transcription. DB cells 
      lack expression of CIITA and all of the MHC-II genes. Stable transfection of DB 
      cells with CIITA expression vectors resulted in coordinate upregulation of MHC-II 
      gene expression, which demonstrates the causal relationship between the lack of 
      CIITA and MHC-II loss. CONCLUSIONS: These data demonstrate that downregulation of 
      MHC-II expression occurs by multiple distinct mechanisms in DLBCL. However, 
      decreases in CIITA expression appear to be the most prevalent mechanism.
FAU - Cycon, Kelly A
AU  - Cycon KA
AD  - Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
FAU - Rimsza, Lisa M
AU  - Rimsza LM
FAU - Murphy, Shawn P
AU  - Murphy SP
LA  - eng
PT  - Journal Article
DEP - 20081209
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (MHC class II transactivator protein)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Cell Line, Tumor
MH  - Chromosomes, Human, Pair 6/genetics/metabolism
MH  - *Gene Expression Regulation, Leukemic/genetics
MH  - HLA-DQ Antigens/*biosynthesis/genetics
MH  - HLA-DR Antigens/*biosynthesis/genetics
MH  - Humans
MH  - Lymphoma, Large B-Cell, Diffuse/genetics/*metabolism
MH  - Neoplasm Proteins/*biosynthesis/genetics
MH  - Nuclear Proteins/*biosynthesis/genetics
MH  - Quantitative Trait Loci/genetics
MH  - Trans-Activators/*biosynthesis/genetics
EDAT- 2008/12/17 09:00
MHDA- 2009/02/20 09:00
CRDT- 2008/12/17 09:00
PHST- 2008/06/05 00:00 [received]
PHST- 2008/09/20 00:00 [revised]
PHST- 2008/10/01 00:00 [accepted]
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/02/20 09:00 [medline]
AID - S0301-472X(08)00465-7 [pii]
AID - 10.1016/j.exphem.2008.10.001 [doi]
PST - ppublish
SO  - Exp Hematol. 2009 Feb;37(2):184-194. doi: 10.1016/j.exphem.2008.10.001. Epub 2008 
      Dec 9.