SKY92 Identifies High‐Risk Newly Diagnosed Multiple Myeloma With Inferior Progression‐Free Survival and Implicates NUF2 as a Candidate Driver
14 affiliations
- 1Multiple Myeloma Research Group Royal College of Surgeons in Ireland Dublin Ireland
- 2Molecular Pathology Laboratory Royal College of Surgeons in Ireland Dublin Ireland
- 3Department of Haematology Beaumont RCSI Cancer Centre Dublin Ireland
- 4Blood Cancer Network Ireland University of Galway Galway Ireland
- 5School of Biological and Chemical Sciences University of Galway Galway Ireland
- 6Department of Haematology Midland Regional Hospital Tullamore Tullamore Ireland
- 7Department of Haematology University Hospital Limerick Limerick Ireland
- 8Haematology Department Galway University Hospital Galway Ireland
- 9Discipline of Advanced Therapies, School of Medicine University of Galway Galway Ireland
- 10Department of Haematology Cork University Hospital Cork Ireland
- 11Department of Haematology University Hospital Waterford Waterford Ireland
- 12Department of Haematology St Vincent's University Hospital Dublin Ireland
- 13SkylineDx Rotterdam the Netherlands
- 14Department of Medicine University of Galway Galway Ireland
Abstract
Objectives: To determine the prevalence and prognostic significance of the SKY92 gene‐expression signature, evaluate minimal/measurable residual disease (MRD), and identify molecular drivers of high‐risk disease in transplant‐eligible newly diagnosed multiple myeloma (TE‐NDMM) patients in the Republic of Ireland.
Methods: Baseline genomic risk was assessed using the MMprofiler microarray in 114 TE‐NDMM patients. MRD was evaluated 100 days after autologous stem cell transplantation using next‐generation sequencing at the International Myeloma Working Group‐recommended sensitivity of 10−5. Differential gene expression and copy number analyses were performed and compared with digital MLPA and retrospective fluorescence in situ hybridisation (FISH).
Results: SKY92 classified 25.4% (29/114) of patients as high‐risk and was associated with inferior progression‐free survival and other adverse disease features. MRD assessment achieved 10−5 sensitivity, although MRD negativity was not associated with SKY92 risk status. High‐risk disease demonstrated enrichment of pathways involved in chromosomal stability and DNA repair. NUF2 emerged as a key independent prognostic marker, showing strong association with high‐risk biology and identifying a potential molecular driver of aggressive disease. Copy number abnormality detection showed high concordance between MMprofiler, digital MLPA, and retrospective FISH.
Conclusions: This first characterisation of SKY92‐defined high‐risk multiple myeloma in Ireland supports integrated genomic profiling for clinical risk stratification and identifies NUF2 as a promising candidate driver, demonstrating that deep profiling of high‐risk disease may help to discover new targets for this challenging entity.
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BibTeX
@article{mcavera2026sky92,
title = {{SKY92 Identifies High‐Risk Newly Diagnosed Multiple Myeloma With Inferior Progression‐Free Survival and Implicates NUF2 as a Candidate Driver}},
author = {Roisin M. McAvera and Izabela Cymer and John Quinn and Phillip T. Murphy and Patrick Thornton and Niamh McAuley and Harmony Black and Omar Abdelzaher and Catherine Duane and Tatiana Cichocka and Eva Szegezdi and Meegahage Perera and Gerard M. Crotty and Michelle Connolly and Aileen Walsh and Ruth Clifford and Janusz Krawczyk and Teresa Meenaghan and Vitaliy Mykytiv and Ezzat Elhassadi and Mark Coyne and Robert J. Cummins and Rowan Kuiper and Michael O'Dwyer and Siobhan V. Glavey},
journal = {European Journal of Haematology},
year = {2026},
month = aug,
doi = {10.1111/ejh.70282},
url = {https://doi.org/10.1111/ejh.70282},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - SKY92 Identifies High‐Risk Newly Diagnosed Multiple Myeloma With Inferior Progression‐Free Survival and Implicates NUF2 as a Candidate Driver
AU - Roisin M. McAvera
AU - Izabela Cymer
AU - John Quinn
AU - Phillip T. Murphy
AU - Patrick Thornton
AU - Niamh McAuley
AU - Harmony Black
AU - Omar Abdelzaher
AU - Catherine Duane
AU - Tatiana Cichocka
AU - Eva Szegezdi
AU - Meegahage Perera
AU - Gerard M. Crotty
AU - Michelle Connolly
AU - Aileen Walsh
AU - Ruth Clifford
AU - Janusz Krawczyk
AU - Teresa Meenaghan
AU - Vitaliy Mykytiv
AU - Ezzat Elhassadi
AU - Mark Coyne
AU - Robert J. Cummins
AU - Rowan Kuiper
AU - Michael O'Dwyer
AU - Siobhan V. Glavey
PY - 2026
DA - 2026/08/07
JO - European Journal of Haematology
DO - 10.1111/ejh.70282
UR - https://doi.org/10.1111/ejh.70282
AB - Objectives: To determine the prevalence and prognostic significance of the SKY92 gene‐expression signature, evaluate minimal/measurable residual disease (MRD), and identify molecular drivers of high‐risk disease in transplant‐eligible newly diagnosed multiple myeloma (TE‐NDMM) patients in the Republic of Ireland. Methods: Baseline genomic risk was assessed using the MMprofiler microarray in 114 TE‐NDMM patients. MRD was evaluated 100 days after autologous stem cell transplantation using next‐generation sequencing at the International Myeloma Working Group‐recommended sensitivity of 10−5. Differential gene expression and copy number analyses were performed and compared with digital MLPA and retrospective fluorescence in situ hybridisation (FISH). Results: SKY92 classified 25.4% (29/114) of patients as high‐risk and was associated with inferior progression‐free survival and other adverse disease features. MRD assessment achieved 10−5 sensitivity, although MRD negativity was not associated with SKY92 risk status. High‐risk disease demonstrated enrichment of pathways involved in chromosomal stability and DNA repair. NUF2 emerged as a key independent prognostic marker, showing strong association with high‐risk biology and identifying a potential molecular driver of aggressive disease. Copy number abnormality detection showed high concordance between MMprofiler, digital MLPA, and retrospective FISH. Conclusions: This first characterisation of SKY92‐defined high‐risk multiple myeloma in Ireland supports integrated genomic profiling for clinical risk stratification and identifies NUF2 as a promising candidate driver, demonstrating that deep profiling of high‐risk disease may help to discover new targets for this challenging entity.
SN - 0902-4441
SN - 1600-0609
ER -