IDH-mutant myeloid neoplasms are associated with seronegative rheumatoid arthritis and innate immune activation

Publikation: Bidrag til tidsskriftLetterForskningfagfællebedømt

  • Lih En Hong
  • Mihir D. Wechalekar
  • Monika Kutyna
  • Annabelle Small
  • Kelly Lim
  • Chloe Thompson-Peach
  • Joule J. Li
  • Rakchha Chhetri
  • Hamish S. Scott
  • Anna Brown
  • Christopher N. Hahn
  • David T. Yeung
  • Nirmal Robinson
  • Ranjeny Thomas
  • Susan Branford
  • Richard J. D'Andrea
  • Saumya E. Samaraweera
  • Mrinal Patnaik
  • Susanna Proudman
  • Daniel Thomas
  • Chung Hoow Kok
  • Mithun V. Shah
  • Devendra K. Hiwase

High prevalence of IDH mutations in seronegative rheumatoid arthritis (RA) with myeloid neoplasm, elevated 2-hydroxyglutarate, dysregulated innate immunity, and proinflammatory microenvironment suggests causative association between IDH mutations and seronegative RA. Our findings merit investigation of IDH inhibitors as therapeutics for seronegative IDH-mutated RA.

OriginalsprogEngelsk
TidsskriftBlood
ISSN0006-4971
DOI
StatusAccepteret/In press - 2024

Bibliografisk note

Funding Information:
The authors are grateful to the patients, their families, Mayo Clinic Acute Leukemia and Myeloid Neoplasms Biobank, and South Australia Cancer Research Biobank. The authors acknowledge editing support by Carla Toop. Some of the data in this publication were produced in the Mayo Clinic Cytogenetics Core Laboratory, which is supported in part by the Mayo Clinic Comprehensive Cancer Center Grant, funded by the National Institutes of Health, National Cancer Institute (P30CA15083). L.E.H. received University of Adelaide Research Training Program Scholarship and Royal Adelaide Hospital (RAH) Research Committee Dawes Top-Up Scholarship. M.V.S. was supported by Mayo Clinic Research Pipeline K2R Transition Award and Bridget Kiely Clinician Career Development in Transplant Research and Mayo Clinic, Rochester. D.K.H. was supported by a National Health and Medical Research Council/Medical Research Future Fund Investigator Grant (MRF1195517), Cancer Australia (#2013617), and Leukemia Foundation Australia (#22007). Contribution: L.E.H. M.D.W. and S.P. collected and annotated autoimmune rheumatic disorders, provided rheumatology expertise, and edited the manuscript; M.K. performed cytokines/chemokines profiling, helped with analysis, and edited the manuscript; A.S. performed monocytes, macrophages, and T-cells subsets analyses and edited the manuscript; K.L. and S.S. performed and analyzed 2-HG levels assay and edited the manuscript; C.T.-P. performed IDH sequencing in isolated T cells and edited the manuscript; R.C. and J.J.L. collated clinical data of myeloid neoplasms and autoimmune rheumatic diseases and edited the manuscript; H.S.S. A.B. S.B. R.J.D. S.E.S. and C.N.H. profiled somatic mutation of the samples and edited the manuscript; D.T.Y. edited the manuscript; N.R. provided expertise in macrophage function and edited the manuscript; R.T. provided expertise on autoimmune rheumatic disease and edited the manuscript; M.P. contributed validation cohort and edited the manuscript; D.T. edited the manuscript, designed experiments, and supervised mass spectrometry analyses and IDH sequencing in isolated T cells; C.H.K. performed statistical analysis and edited the manuscript; M.V.S. contributed the patient data and edited the manuscript; and D.K.H. designed the project, secure funding, supervised, analyzed results, and wrote the manuscript.

Funding Information:
Some of the data in this publication were produced in the Mayo Clinic Cytogenetics Core Laboratory, which is supported in part by the Mayo Clinic Comprehensive Cancer Center Grant, funded by National Cancer Institute ( P30CA15083 ). L.E.H. received University of Adelaide Research Training Program Scholarship and Royal Adelaide Hospital (RAH) Research Committee Dawes Top-Up Scholarship. M.V.S. was supported by Mayo Clinic Research Pipeline K2R Transition Award and Bridget Kiely Clinician Career Development in Transplant Research and Mayo Clinic , Rochester. D.K.H. was supported by a National Health and Medical Research Council / Medical Research Future Fund Investigator Grant ( MRF1195517 ), Cancer Australia (# 2013617 ), and Leukemia Foundation Australia (# 22007 ).

Publisher Copyright:
© 2024 American Society of Hematology

ID: 388539360