Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias: Combination analysis with cDNA expression array and tissue microarray

To investigate the lymphomagenesis of NK/T lymphoma, we comprehensively and systematically analyzed the expression pattern of the human NK/T cell line (NK-YS) genome by cDNA expression array and tissue microarray. We detected significant changes in the gene expression of NK-YS cell line: an increase in 18 and a decrease in 20 genes compared to normal NK cells or peripheral blood mononuclear cells. Among these genes, we found a strong decrease in hematopoietic cell specific protein-tyrosine-phosphatase SHPTP1 (SHP1) mRNA by cDNA expression array and reverse transcriptase-polymerase chain reacti on. Further analysis with standard immunohistochemistry and tissue microarr ay, which used 207 paraffin-embedded specimens of various kinds of malignan t lymphomas, showed that 100% of NK/T lymphoma specimens and more than 95% of various types of malignant lymphoma. were negative for SHP1 protein expr ession. On the other hand, SHP1 protein was strongly expressed in the mantl e zone and interfollicular zone lymphocytes in reactive lymphoid hyperplasi a specimens. In addition, various kinds of hematopoietic cell lines, partic ularly the highly aggressive lymphoma/leukemia lines, lacked SHP1 expressio n in vitro, suggesting that loss of SHP1 expression may be related to not o nly malignant transformation, but also tumor cell aggressiveness. SHP1 expr ession could not be induced in either of two NK/T cell fines by phorbol est er, suggesting that genetic impairment or modification with methylation of SHP1 DNA could be one of the critical events in the pathogenesis of NK/T ly mphoma. This evidence strongly suggests that loss of SHP1 gene expression p lays an important role in multistep tumorigenesis, possibly as an anti-onco gene in the wide range of lymphomas/leukemias as well as NK/T lymphomas.