Development of a predictive system of the sensitivity for L-asparaginase in tumor by monoclonal antibody

2015 Fiscal Year Final Research Report

• Project/Area Number: 24590713
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Aichi Medical University
• Principal Investigator: Kitoh Toshiyuki 愛知医科大学, 医学部, 准教授 (50243027)
• Co-Investigator(Kenkyū-buntansha): YOKOI TOYOHARU 愛知医科大学, 医学部, 教授 (40200886) ; TSURUSAWA MASAHITO 愛知医科大学, 医学部, 教授 (90172064) ; KATO HIDEFUMI 愛知医科大学, 医学部, 教授 (40298584)
• Co-Investigator(Renkei-kenkyūsha): HAMAKUBO TAKAO 東京大学, 先端科学技術研究センター, 教授 (90198797)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 分子標的療法 / アミノ酸要求性 / 選択毒性 / 抗がん剤 / 細胞死 / 酵素製剤 / 感受性予測 / アミノ酸代謝

Outline of Final Research Achievements

Due to the lack of rapid upregulation of asparagine synthetase (ASNS) in ALL cells, they are preferentially killed by ASNase-induced asparagine depletion. The purpose of this study was to examine the usefulness of a rapid flow cytometric assay that measure ASNS protein in whole cells to predict sensitivity and resistance to ASNase. ASNS expression evaluated by cytosolic flow cytometry with the Z5808 monoclonal antibody (McAb) (Hybridoma, 2012) significantly correlated with ASNS activity in leukaemia cell lines. The ASNS protein level was inversely correlated with sensitivity to ASNase in both leukaemia cell lines and primary leukaemia cells. We have shown that ASNS protein expression measured by flow cytometry assay strongly predicts ASNase activity in leukaemia cells and that lower levels of ASNS protein found in AML-M1, M5 and M7 subtypes. The utility of using flow cytometry to measure ASNS levels in clinical samples and the future potential of this methodology is promising.

Free Research Field

がん化学療法