Expression of growth factor/receptor genes in postthymic T cell malignancies.
This study was undertaken to explain the molecular basis for the diverse pathology and clinical behavior of postthymic T cell malignancies. Total cellular RNAs were extracted from four HTLV-1 positive and ten HTLV-1-negative T cell lymphomas and cell lines, and investigated for homology with cloned DNA probes specific for interleukin-2 (IL-2), IL-2 receptor (IL-2R), transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), and epidermal growth factor receptor (EGF-R). Tumor cells associated with clinically high grade HTLV-1-positive adult T cell leukemia (ATL) and large cell morphology (T immunoblastic lymphomas) were found to have higher levels of expression of IL-2 and TGF-beta genes than low grade T cell neoplasms (mycosis fungoides and Sezary's syndrome). High expression of IL-2R gene was restricted to Ki-1-positive lymphomas and to one ATL. Cell lines corresponding to the advanced stage of a cutaneous T cell lymphoma (CTCL) showed enhanced expression of PDGF. Therefore, high grade T cell malignancies had consistently elevated expression of growth factor/receptor (GF/R) genes. Expression of EGF-R was negligible in all T cell malignancies. An inverse relationship was found between the expression of T cell antigen receptor (differentiation antigen) and GF/R (activation antigen) genes, accounting for the frequent aberrant expression of T cell antigens in high grade T cell lymphomas. The results suggest that post-thymic T cell malignancies derived from activated T cells produce and secrete GF, conferring a growth advantage on neoplastic T cells, and correlating well with their histologic subtype and clinical behavior.
Su
I J
IJ
Department of Pathology, National Taiwan University Hospital, Taipei, Republic of China.
Kadin
M E
ME
D015152:Blotting, Northern; D006133:Growth Substances / Q000096:biosynthesis*; D015490:HTLV-I Infections / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism* / Q000382:microbiology; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000378:metabolism* / Q000382:microbiology; D011975:Receptors, Mitogen / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D011975:Receptors, Mitogen; D013755:Tetradecanoylphorbol Acetate