Using the in vitro drug sensitivity test to identify candidate treatments for transient abnormal myelopoiesis. (23rd November 2021)

• Record Type: Journal Article
• Authors: Yokosuka, Tomoko; Ito, Mieko; Yoshino, Yuki; Hirose, Ayana; Nakamura, Wataru; Sakurai, Yukari; Hayashi, Akiko; Fujita, Sachio; Miyagawa, Naoyuki; Keino, Dai; Iwasaki, Fuminori; Hamanoue, Satoshi; Yanagimachi, Masakatsu; Goto, Shoko; Nagai, Jun‐ichi; Ueno, Hiroo; Takita, Junko; Tanaka, Yukichi; Taga, Takashi; Goto, Hiroaki
• Is Part Of: British journal of haematology. Volume 196:Number 3(2022)
• Page Start: 764
• Page End: 768
• Publication Date: 2021-11-23
• Subjects: transient abnormal myelopoiesis -- Down syndrome -- in vitro drug sensitivity test -- mitogen‐activated protein kinase kinase (MAP2K) inhibitor -- glucocorticoid; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.17970
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: Approximately 20% of patients with transient abnormal myelopoiesis (TAM) die due to hepatic or multiorgan failure. To identify potential new treatments for TAM, we performed in vitro drug sensitivity testing (DST) using the peripheral blood samples of eight patients with TAM. DST screened 41 agents for cytotoxic properties against TAM blasts. Compared with the reference samples of healthy subjects, TAM blasts were more sensitive to glucocorticoids, the mitogen‐activated protein kinase kinase (MAP2K) inhibitor trametinib, and cytarabine. Our present results support the therapeutic potential of glucocorticoids and the role of the RAS/MAP2K signalling pathway in TAM pathogenesis.