Evidence map›Paper›PMID 40360497›Full record

Trial reportNature communications2025

Clinical response to azacitidine in MDS is associated with distinct DNA methylation changes in HSPCs.

Julie A I Thoms, Feng Yan, Henry R Hampton, Sarah Davidson, Swapna Joshi, Jesslyn Saw, Chowdhury H Sarowar, Xin Ying Lim, Andrea C Nunez, Purvi M Kakadia and 46 more

Abstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

56 authors.

Julie A I ThomsSchool of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia. j.thoms@unsw.edu.au.ORCID http://orcid.org/0000-0002-4876-7230
Feng YanBioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0002-8848-1739
Henry R HamptonSchool of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-1121-8764
Sarah DavidsonANU Clinical Hub for Interventional Research (CHOIR), John Curtin School of Medical Research, Canberra, ACT, Australia.
Swapna JoshiSchool of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
Jesslyn SawAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.
Chowdhury H SarowarSchool of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
Xin Ying LimSchool of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
Andrea C NunezSchool of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
Purvi M KakadiaLeukaemia & Blood Cancer Research Unit, Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Golam Sarower BhuyanSchool of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
Xiaoheng ZouSchool of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.
Mary NguyenSchool of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.
Elaheh S GhodousiSchool of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.
Forrest C KochSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Fatemeh VafaeeSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-7521-2417
I Richard ThompsonComprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.ORCID http://orcid.org/0000-0002-9554-550X
Mohammad M KarimiComprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.ORCID http://orcid.org/0000-0001-5017-1252
Russell PickfordBioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia.
Mark J RafteryBioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia.
Sally HoughKirby Institute, University of New South Wales, Sydney, NSW, Australia.
Griselda BucklandANU Clinical Hub for Interventional Research (CHOIR), John Curtin School of Medical Research, Canberra, ACT, Australia.
Michelle BaileyKirby Institute, University of New South Wales, Sydney, NSW, Australia.
Yuvaraj GhodkeANU Clinical Hub for Interventional Research (CHOIR), John Curtin School of Medical Research, Canberra, ACT, Australia.ORCID http://orcid.org/0009-0003-4479-5888
Noorul AbsarKirby Institute, University of New South Wales, Sydney, NSW, Australia.
Lachlin VaughanSchool of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
Leonardo PasalicWestmead Hospital, Sydney, NSW, Australia.
Chun Y FongDepartment of Haematology, Austin Health, Melbourne, VIC, Australia.
Melita KenealyCabrini Hospital, Melbourne, VIC, Australia.
Devendra K HiwaseDepartment of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0002-6666-3056
Rohanna I StoddartUniversity of New South Wales, Sydney, NSW, Australia.
Soma MohammedICPMR, Department of Haematology, Westmead Hospital, Sydney, NSW, Australia.
Linda LeeRoyal North Shore Hospital, Sydney, NSW, Australia.
Freda H PassamHaematology Research Group, Heart Research Institute, Sydney, NSW, Australia.
Stephen R LarsenInstitute of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Kevin J SpringMedical Oncology Group, Liverpool Clinical School, School of Medicine, Western Sydney University and Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia.ORCID http://orcid.org/0000-0003-0601-924X
Kristen K SkarrattSydney Medical School, Nepean Clinical School, Faculty of Medicine and Health, University of Sydney, Nepean Hospital, Kingswood, NSW, Australia.ORCID http://orcid.org/0000-0003-4971-2773
Patricia RebeiroBlacktown Hospital, Sydney, NSW, Australia.
Peter PresgraveWollongong Hospital, Wollongong, NSW, Australia.
William S StevensonRoyal North Shore Hospital, Sydney, NSW, Australia.
Silvia LingLiverpool Hospital, Sydney, NSW, Australia.
Campbell TileyCentral Coast Health, Gosford Hospital, Gosford, NSW, Australia.
Stephen J FullerSydney Medical School, Nepean Clinical School, Faculty of Medicine and Health, University of Sydney, Nepean Hospital, Kingswood, NSW, Australia.ORCID http://orcid.org/0000-0003-4637-7391
Fernando RoncolatoSt. George Hospital, Sydney, NSW, Australia.ORCID http://orcid.org/0009-0007-9955-5928
Anoop K EnjetiDepartment of Haematology, Calvary Mater Hospital, Waratah, NSW, Australia.
Dirk HoenemannOtway Pharmaceutical Development and Consulting Pty Ltd, Forrest, VIC, Australia.
Charlotte LemechScientia Clinical Research, Medical Oncology, Prince of Wales Hospital, Sydney, NSW, Australia.
Christopher J JollySchool of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.
Stefan K BohlanderLeukaemia & Blood Cancer Research Unit, Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.ORCID http://orcid.org/0000-0002-2202-9088
David J CurtisAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0001-9497-0996
Jason W H WongSchool of Biomedical Sciences, The University of Hong Kong, Hong Kong, SAR, China.
Ashwin UnnikrishnanSchool of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-5168-8755
Mark HertzbergDepartment of Clinical Haematology, Prince of Wales Hospital, Sydney, NSW, Australia.
Jake OlivierSchool of Mathematics and Statistics, University of New South Wales, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-3144-4507
Mark N PolizzottoANU Clinical Hub for Interventional Research (CHOIR), John Curtin School of Medical Research, Canberra, ACT, Australia. mark.polizzotto@anu.edu.au.
John E PimandaSchool of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia. jpimanda@unsw.edu.au.ORCID http://orcid.org/0000-0002-0509-8962

Funding

Anthony Rothe Memorial Trust (A. Rothe Memorial Trust) RG182042, RG202657, RG213236Celgene (Celgene Corporation) RG172029Department of Health | National Health and Medical Research Council (NHMRC) RG170246, RG211412
6 · The paper itself

Abstract

Hypomethylating agents are frontline therapies for myelodysplastic neoplasms (MDS), yet clinical responses remain unpredictable. We conducted a phase 2 trial comparing injectable and oral azacitidine (AZA) administered over one or three weeks per four-week cycle, with the primary objective of investigating whether response is linked to in vivo drug incorporation or DNA hypomethylation. Our findings show that injection results in higher drug incorporation, but lower DNA demethylation per cycle, while global DNA methylation levels in mononuclear cells are comparable between responders and non-responders. However, hematopoietic stem and progenitor cells (HSPCs) from responders exhibit distinct baseline and early treatment-induced CpG methylation changes at regulatory regions linked to tissue patterning, cell migration, and myeloid differentiation. By cycle six-when clinical responses typically emerge-further differential hypomethylation in responder HSPCs suggests marrow adaptation as a driver of improved hematopoiesis. These findings indicate that intrinsic baseline and early drug-induced epigenetic differences in HSPCs may underlie the variable clinical response to AZA in MDS.

Indexed as

Antimetabolites, AntineoplasticAzacitidineDNA MethylationHematopoietic Stem CellsMyelodysplastic SyndromesAdministration, OralAdultAgedAged, 80 and overCpG IslandsEpigenesis, GeneticFemaleHumansMaleMiddle AgedTreatment OutcomeAntimetabolites, AntineoplasticAzacitidine

Identifiers

PMID40360497
PMCPMC12075701

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.