title: The methylthioadenosine phosphorylase gene is frequently co-deleted with the p16INK4a gene in acute type adult T-cell leukemia.
abstract: 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.
authors.affiliation: Department of Medicine, Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, USA. yayuyu@clin.medic.mie-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Hori
authors.forename: H
authors.initials: H
authors.lastname: Hori
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: C J
authors.initials: CJ
authors.lastname: Carrera
authors.forename: M
authors.initials: M
authors.lastname: Tomonaga
authors.forename: S
authors.initials: S
authors.lastname: Kamihira
authors.forename: D A
authors.initials: DA
authors.lastname: Carson
authors.forename: T
authors.initials: T
authors.lastname: Nobori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics*; D008875:Middle Aged; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase