Interruption of p16 gene expression in adult T‐cell leukaemia/lymphoma: clinical correlation

• Published in: British journal of haematology 2003-07, Vol.122 (2), p.253-259
• Main Authors: Takasaki, Yumi, Yamada, Yasuaki, Sugahara, Kazuyuki, Hayashi, Tomomi, Dateki, Natsuko, Harasawa, Hitomi, Kawabata, Shigeru, Soda, Hiroshi, Ikeda, Shuichi, Tomonaga, Masao, Kamihira, Shimeru
• Format: Article
• Language: English
• Subjects: Adult; ATLL; Biological and medical sciences; Blotting, Western - methods; Case-Control Studies; Cyclin-Dependent Kinase Inhibitor p16 - analysis; Disease Progression; DNA - analysis; Gene Deletion; Genes, p16; Hematologic and hematopoietic diseases; Hematology; HTLV; Humans; Leukemia, T-Cell - genetics; Leukemia, T-Cell - mortality; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; p16; Polymerase Chain Reaction - methods; Prognosis; real‐time PCR; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Survival Rate
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2003.04377.x

We previously reported that p16 gene deletion is involved in the development and progression of adult T‐cell leukaemia/lymphoma (ATLL). To further investigate the significance of this gene in ATLL, we examined its expression status in 63 patients. Samples were analysed at DNA, mRNA and protein levels using real‐time polymerase chain reaction (PCR), reverse transcription (RT)‐coupled real‐time PCR and Western blot respectively. Twenty‐four patients (38·1%) were p16 gene negative, and they showed significantly shorter survival than p16‐gene‐positive patients. The expression of p16 mRNA in p16‐gene‐positive patients varied greatly, and cells from some patients showed up to several hundredfold higher expression than normal lymphocytes. Surprisingly, among 17 patients examined for p16 protein expression, all four patients with unusually high mRNA lacked p16 protein expression, indicating that p16 protein production in these patients was interrupted at the translational level. Moreover, these patients showed significantly shorter survival than p16‐protein‐positive patients. These results indicate that the presence of p16 gene and p16 mRNA do not necessarily indicate the production of p16 protein in ATLL, and that loss of p16 protein function is involved in progression of ATLL.