Evidence map›Paper›PMID 40321765›Full record

ArticleResearch square2025

Epigenetic Plasticity Drives Carcinogenesis and Multi-Therapy Resistance in Multiple Myeloma.

Rafael Renatino Canevarolo, Praneeth Reddy Sudalagunta, Mark B Meads, Maria Silva, Xiaohong Zhao, Dario Magaletti, Raghunandan Reddy Alugubelli, Gabriel DeAvila, Erez Persi, Francesco Maura and 24 more

Abstract readPreprint
In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

34 authors.

Rafael Renatino CanevaroloDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.ORCID 0000-0002-8722-8512
Praneeth Reddy SudalaguntaDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.ORCID 0000-0003-1283-9332
Mark B MeadsDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Maria SilvaDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Xiaohong ZhaoDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Dario MagalettiDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Raghunandan Reddy AlugubelliDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Gabriel DeAvilaDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Erez PersiComputational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Francesco MauraDivision of Myeloma, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Elissa T BellDepartment of Biological Science, Florida State University, Tallahassee, FL, USA.ORCID 0000-0002-0171-115X
Ryan T BishopDepartment of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Christopher L CubittImmune Monitoring Core, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.ORCID 0000-0001-6343-7451
Samer S SansilCancer Pharmacokinetics and Pharmacodynamics Core, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.ORCID 0000-0001-8372-7149
Wei ZhangDepartment of Computer Science, University of Central Florida, Orlando, Florida, USA.
Jamie K TeerDepartment of Biostatistics & Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.ORCID 0000-0003-4513-0282
Mingxiang TengDepartment of Biostatistics & Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.ORCID 0000-0002-8536-8941
Sean J YoderMolecular Genomics Core, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Erin M SiegelDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Bijal D ShahDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Taiga NishihoriDepartment of Blood & Marrow Transplant and Cellular Therapies, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Lori A HazlehurstDepartment of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, USA.
Conor C LynchDepartment of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Ola LandgrenDivision of Myeloma, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.ORCID 0000-0001-6485-4839
Oliver HamptonAster Insights, Tampa, FL, USA.
Robert A GatenbyDepartments of Radiology and Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.ORCID 0000-0002-1621-1510
Daniel M SullivanDepartment of Blood & Marrow Transplant and Cellular Therapies, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Jason B BrayerDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
William S DaltonDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
John L ClevelandDepartment of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.ORCID 0000-0002-7561-9065
Melissa AlsinaDepartment of Blood & Marrow Transplant and Cellular Therapies, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Rachid BazDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Kenneth H ShainDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Ariosto Siqueira SilvaDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.ORCID 0000-0003-3237-9986

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
Tumor Biology Research ProgramP30CA240139 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Stephen D. Nimer · 2019 to 2026
$24.1M
"Research Supplement to Promote Diversity in Health-Related Research", as part of Moffitt PS-OC, "Cancer as a Complex adaptive System"U54CA193489 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI ANDERSON, ALEXANDER ROBERTSON ALLAN, GATENBY, ROBERT A · 2015 to 2020
$12.5M
Targeting CD44-mediated calcium signaling for the treatment of relapsed myelomaR01CA195727 · NCI · WEST VIRGINIA UNIVERSITY · PI HAZLEHURST, LORI A · 2015 to 2019
$1.7M
NCI NIH HHS P30 CA076292NCI NIH HHS P30 CA240139NCI NIH HHS R01 CA195727NCI NIH HHS U54 CA193489
6 · The paper itself

Abstract

We demonstrate that carcinogenesis and multi-therapy resistance in multiple myeloma (MM)-a treatable yet incurable plasma cell malignancy-are driven by epigenetic dysregulation. In this new paradigm, genomic and cytogenetic events unlock epigenetic plasticity, reshaping MM cell biology to evade tumor microenvironment constraints and therapeutic pressure. These conclusions are derived from a newly assembled cohort of nearly 1,000 patients, spanning premalignant to late-stage refractory MM, comprehensively characterized at molecular and clinical levels. Our findings provide a unifying framework to explain inter-patient genomic heterogeneity and the emergence of therapy resistance in sequential samples without new genomic alterations. In conclusion, we propose targeting epigenetic plasticity-mediated plasma cell evasion as a promising therapeutic strategy in MM.

Indexed as

carcinogenesischromatin accessibilityepigenetic plasticityepigeneticsH3K27acH3K27me3malignant transformationMGUSmultiple myelomamulti-therapy resistancepioneer transcription factorsingle cell multiomicssmoldering multiple myelomasuper enhancertherapeutic targettranscription dysregulation

Identifiers

PMID40321765
PMCPMC12048002

What OpenQuestion holds

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Registered trials

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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.