Hori Y, Hori H, Yamada Y, Carrera C J, Tomonaga M, Kamihira S, Carson D A, Nobori T
Department of Medicine, Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, USA.
Int J Cancer. 1998 Jan 5;75(1):51-6. doi: 10.1002/(sici)1097-0215(19980105)75:1<51::aid-ijc9>3.0.co;2-0.
Adult T-cell leukemia (ATL) is a retrovirus-associated leukemia with poor prognosis and often has deletions of the p16INK4a and p15INK4b genes on chromosome 9p21. The gene for methylthioadenosine phosphorylase (MTAP), a purine and methionine metabolic enzyme, resides approximately 100 Kb telomeric to the p16INK4a gene and is frequently co-deleted with the tumor suppressor gene in a variety of cancers. This enzyme deficiency can be exploited for selective chemotherapy with de novo purine synthesis inhibitors and/or methionine depletion. To determine whether ATL can be a candidate for selective chemotherapy based on genetic alterations on chromosome 9p21, we analyzed the MTAP gene in 41 samples from ATL patients (27 acute type and 14 chronic type ATL) and 3 cell lines established from ATL patients. Five samples from the acute type had deletions of the MTAP gene (4 total deletions and 1 partial deletion of exons 6-8). The MTAP gene was always co-deleted with p16INK4a. No deletion of the MTAP gene was detected in samples from the chronic type. Of 3 cell lines, 2 showed partial deletions of exons 5-8 of the MTAP gene, and 1 lost all exons. The p16INK4a gene was deleted in all cell lines. In conclusion, deletions of the MTAP gene were found in 5 of 27 acute type ATL samples. Acute type ATL with MTAP deficiency can be a good candidate for selective chemotherapy by depleting purines and/or methionine.
成人T细胞白血病（ATL）是一种与逆转录病毒相关的白血病，预后较差，常伴有9号染色体p21区域的p16INK4a和p15INK4b基因缺失。甲硫腺苷磷酸化酶（MTAP）是一种嘌呤和甲硫氨酸代谢酶，其基因位于p16INK4a基因端粒约100 Kb处，在多种癌症中常与肿瘤抑制基因共同缺失。这种酶缺乏可用于嘌呤从头合成抑制剂和/或甲硫氨酸耗竭的选择性化疗。为了确定ATL是否可作为基于9号染色体p21基因改变的选择性化疗候选对象，我们分析了41例ATL患者（27例急性型和14例慢性型ATL）的样本以及3株从ATL患者建立的细胞系中的MTAP基因。急性型的5个样本存在MTAP基因缺失（4个完全缺失和1个外显子6 - 8的部分缺失）。MTAP基因总是与p16INK4a共同缺失。慢性型样本中未检测到MTAP基因缺失。在3株细胞系中，2株显示MTAP基因外显子5 - 8的部分缺失，1株失去了所有外显子。所有细胞系中p16INK4a基因均缺失。总之，在27例急性型ATL样本中有5例发现MTAP基因缺失。MTAP缺乏的急性型ATL可作为通过消耗嘌呤和/或甲硫氨酸进行选择性化疗的良好候选对象。
