SSBD:database

368-Yabushita-Decitabine

Author reviewed

Time-lapse images of MDS-derived AML cell lines treated with decitabine

SSBD:OMERO.gallery SSBD:OMERO

SSBD:downloads

Project ID

368-Yabushita-Decitabine

Project SID

368

Title

Time-lapse images of MDS-derived AML cell lines treated with decitabine

Description

Decitabine (DAC) is clinically used to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Genome-wide CRISPR-dCas9 activation screen using MDS-derived AML cells indicates that mitotic regulation is critical for DAC resistance. DAC strongly induces abnormal mitosis (abscission failure or tripolar mitosis) in human myeloid tumors at clinical concentrations, especially in those with TP53 mutations or antecedent hematological disorders. This DAC-induced mitotic disruption and apoptosis are significantly attenuated in DNMT1-depleted cells. In contrast, overexpression of Dnmt1, but not the catalyt- ically inactive mutant, enhances DAC-induced mitotic defects in myeloid tumors. The authors also demonstrate that DAC-induced mitotic disruption is enhanced by pharmacological inhibition of the ATR-CLSPN-CHK1 pathway. These data challenge the current assumption that DAC inhibits leukemogenesis through DNMT1 inhibition and subsequent DNA hypomethylation and highlight the potent activity of DAC to disrupt mitosis through aberrant DNMT1-DNA covalent bonds.

Submission Date

2024-11-07

Opened Date

Release Date

2025-04-10

Update Date

Kind

Image datasets

License

CC BY

Project URL

Project DOI

Metadata Version

Template Version

Funding Information

This work was supported by Grant-in-Aid for Scientific Research (19H05651, D.K.; 20H00537, T.K.; 19H03685, 22H03100, S.G.), Grant-in-Aid for Scientific Research on Innovative Areas (21H00272, A.N.), Grant-in-Aid for Challenging Research (Exploratory) (22K19540, S.G.), Fund for the Promotion of Joint Inter- national Research (Fostering Joint International Research [B]) (22KK0127, S.G.), Grant-in-Aid for Japan Society for the Promotion of Science (JSPS)　research fellow DC1 (19J21723, T.Y.), Japan Agency for Medical Research and Development (JP21zf0127001, T.S.), JST Core Research for Evolutional Scienece and Technology (JPMJCR2123, T.S.; JPMJCR21E6, T. Fukaga- wa),The Uehara Memorial Foundation (T.C.), and The Kanae Foundation for the Promotion of Medical Science (D.K).

Total

44 files / 40.3 GB

Image datasets

zipped 22 files / 13.7 GB, raw image 22 files / 26.6 GB, total 44 files / 40.3 GB

Quantitative datasets

zipped 0 files / 0 bytes, raw bdml 0 files / 0 bytes, total 0 files / 0 bytes

Biosample

Organism

Homo sapiens ( NCBITaxon:9606 )

Strain

Cell

Cell line

MDS-L-2007 (a human secondery myeloid leukemia cell line derived from an MDS (myelodysplastic syndrome) cell line, MDS-92)

HL-60

MeSH

Cell Line, Tumor ( D018613 )

Cell Division, Cell Cycle

HL-60 Cells ( D018613 )

Ontology

Anatomical Entity

UBERON

Biological Process

cell division, cell cycle ( GO:0007049 )

Cellular Component

Molecular Function

Medical Subject Headings

Cell Line, Tumor ( D018613 )

Cell Division, Cell Cycle

HL-60 Cells ( D018613 )

Imaging Method

Method involved in biological imaging

confocal microscopy ( FBbi:00000251 )

Paper DOI / Paper URL

PMID: 37714156 , doi: 10.1016/j.celrep.2023.113098

People

Contact

Susumu Goyama

The University of Tokyo

Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences

Imaging dataset contributor

Tomohiro Yabushita (The University of Tokyo)

Takumi Chinen (The University of Tokyo)

Daiju Kitagawa (The University of Tokyo)

Quantitative dataset contributor

Image datasets

Quantitative datasets

Dataset List

Thumbnail

Dataset

Organism

Kind / Links

Fig2_MDS_DAC0.25_1

Homo sapiens ( NCBITaxon:9606 )