Kato, Motohiro
Mayo Clinic
Department of Pediatrics, The University of Tokyo, Tokyo, Japan.
Citations 2
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update
Maillard, M., Schwab, Matthias, Whirl-Carrillo, Michelle, Moyer, AM , Suarez‐Kurtz, Guilherme , Pui, CH, Stein, C Michael, Klein, Teri E. , Spahn, Claire , Kwon, Sooyeon, Boer, Nanne K de, Ahmad, Tariq, Antillon-Klussmann, Federico Guillermo, Caudle, Kelly E. , Yeoh, Allen E J, Schmiegelow, K., Yang, Jun J, Schwab, Matthias , Maillard, Maud , Maillard, Maud , Schwab, Matthias , Whirl-Carrillo, Michelle , Caudle, Kelly E , Kato, Motohiro , Klein, Teri E , Whirl‐Carrillo, Michelle , Stein, C. Michael, Hartono, Juanda Leo , Ahmad, Tariq , Antillon‐Klussmann, Federico Guillermo, Kato, Motohiro , Yeoh, Allen Eng Juh
Clinical Pharmacology & Therapeutics | January 31, 2026 | Volume: 119 | Issue: 4 | Pages: 916-927
Thiopurine methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) are key enzymes that catabolize thiopurines. Decreased or no‐function alleles in TPMT and NUDT15 are associated with reduced or no enzyme activity and predictive of pronounced adverse effects, including severe myelosuppression, that may occur among individuals treated with standard doses of thiopurines. Genetic variants in these genes are present in all world populations; however, their frequency varies by ancestry. In this updated guideline, we provide recommendations for adjusting starting doses of mercaptopurine, thioguanine, and azathioprine based on TPMT and NUDT15 genotypes, including for individuals with variants in both genes (updates on www.clinpgx.org ).
Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome–negative myeloproliferative neoplasms
Thoennissen, Nils H., Krug, Utz , Lee, Dhong Hyun Tony, Kawamata, Norihiko , Iwanski, Gabriela B., Weiss, Tamara, Nowak, Daniel , Koren‐Michowitz, Maya , Kato, Motohiro , Sanada, Masashi , Nagler, Arnon , Raynaud, Sophie , Müller‐Tidow, Carsten , Haferlach, Torsten , Gilliland, D. Gary, Tefferi, Ayalew , Koeffler, H. Phillip , Lasho, Terra L. , Shih, Lee‐Yung , Mesa, Ruben A. , Ogawa, Seishi , Kato, Motohiro
Blood | January 13, 2010 | Volume: 115 | Issue: 14 | Pages: 2882-2890
Abstract Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and primary myelofibrosis show an inherent tendency for transformation into leukemia (MPN-blast phase), which is hypothesized to be accompanied by acquisition of additional genomic lesions. We, therefore, examined chromosomal abnormalities by high-resolution single nucleotide polymorphism (SNP) array in 88 MPN patients, as well as 71 cases with MPN-blast phase, and correlated these findings with their clinical parameters. Frequent genomic alterations were found in MPN after leukemic transformation with up to 3-fold more genomic changes per sample compared with samples in chronic phase (P < .001). We identified commonly altered regions involved in disease progression including not only established targets (ETV6, TP53, and RUNX1) but also new candidate genes on 7q, 16q, 19p, and 21q. Moreover, trisomy 8 or amplification of 8q24 (MYC) was almost exclusively detected in JAK2V617F− cases with MPN-blast phase. Remarkably, copy number–neutral loss of heterozygosity (CNN-LOH) on either 7q or 9p including homozygous JAK2V617F was related to decreased survival after leukemic transformation (P = .01 and P = .016, respectively). Our high-density SNP-array analysis of MPN genomes in the chronic compared with leukemic stage identified novel target genes and provided prognostic insights associated with the evolution to leukemia.