Using the in vitro drug sensitivity test to identify candidate treatments for transient abnormal myelopoiesis

Br J Haematol. 2022 Feb;196(3):764-768. doi: 10.1111/bjh.17970. Epub 2021 Nov 23.

Abstract

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.

Keywords: Down syndrome; glucocorticoid; in vitro drug sensitivity test; mitogen-activated protein kinase kinase (MAP2K) inhibitor; transient abnormal myelopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers
  • Cell Culture Techniques
  • Cells, Cultured
  • Drug Screening Assays, Antitumor* / methods
  • Female
  • Gene Expression Regulation / drug effects
  • High-Throughput Nucleotide Sequencing
  • High-Throughput Screening Assays
  • Humans
  • Immunohistochemistry
  • Leukemoid Reaction / drug therapy*
  • Leukemoid Reaction / etiology
  • Leukocytes, Mononuclear / drug effects
  • Male
  • Middle Aged
  • Myelopoiesis / drug effects*

Substances

  • Antineoplastic Agents
  • Biomarkers