TY - JOUR
T1 - Cell origin of pyothorax-associated lymphoma
T2 - A lymphoma strongly associated with Epstein-Barr virus infection
AU - Takakuwa, T.
AU - Tresnasari, K.
AU - Rahadiani, N.
AU - Miwa, H.
AU - Daibata, M.
AU - Aozasa, K.
N1 - Funding Information:
This study was supported by grants from the Ministry of Education, Science, Culture, and Sports, Japan (14031213, 14770073, 15026209, 15406013, 15590340, 16390105 and 18014015).
PY - 2008/1/1
Y1 - 2008/1/1
N2 - Pyothorax-associated lymphoma (PAL) is an Epstein-Barr virus (EBV)-associated B cell lymphoma developing in the pleural cavity affected by chronic pyothorax. To clarify the cell origin of PAL, the expression of immunoglobulin heavy (IgH) and light chains in relation to somatic hypermutations (SHMs) of rearranged Ig heavy- and light-chain variable (IgVH, IgVL) genes was examined using cell lines as well as clinical samples. SHMs without ongoing mutations of the IgVH gene were found in all PAL cell lines and clinical samples available for sequencing, indicating PAL to be derived from B cells at the postgerminal center (GC) stage of the differentiation process. They could be subdivided into post-GC cells with potentially productive IgVH genotypes (Group 1) and with sterile IgVH genotypes (Group 2). IgH expression was abrogated in Group 2 as expected and also in two cell lines in Group 1. DNA demethylation experiments with 5-aza-dC induced expression of IgH mRNA and protein in these cell lines. Most PAL cells were derived from crippled post-GC cells, which usually could not survive. Transformation of such B cells through EBV infection might provide a basis for the development of PAL with additional genetic changes.
AB - Pyothorax-associated lymphoma (PAL) is an Epstein-Barr virus (EBV)-associated B cell lymphoma developing in the pleural cavity affected by chronic pyothorax. To clarify the cell origin of PAL, the expression of immunoglobulin heavy (IgH) and light chains in relation to somatic hypermutations (SHMs) of rearranged Ig heavy- and light-chain variable (IgVH, IgVL) genes was examined using cell lines as well as clinical samples. SHMs without ongoing mutations of the IgVH gene were found in all PAL cell lines and clinical samples available for sequencing, indicating PAL to be derived from B cells at the postgerminal center (GC) stage of the differentiation process. They could be subdivided into post-GC cells with potentially productive IgVH genotypes (Group 1) and with sterile IgVH genotypes (Group 2). IgH expression was abrogated in Group 2 as expected and also in two cell lines in Group 1. DNA demethylation experiments with 5-aza-dC induced expression of IgH mRNA and protein in these cell lines. Most PAL cells were derived from crippled post-GC cells, which usually could not survive. Transformation of such B cells through EBV infection might provide a basis for the development of PAL with additional genetic changes.
UR - http://www.scopus.com/inward/record.url?scp=40749102504&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2405059
DO - 10.1038/sj.leu.2405059
M3 - Article
C2 - 18079737
AN - SCOPUS:40749102504
SN - 0887-6924
VL - 22
SP - 620
EP - 627
JO - Leukemia
JF - Leukemia
IS - 3
ER -
