Authors
Naroa Barrena, Edurne San José-Enériz, Luis V Valcárcel, Danel Olaverri-Mendizabal, Estibaliz Urizar-Compains, Leire Garate, Estíbaliz Miranda, Paula Rodriguez-Marquez, Romika Kumari, Patxi San Martín-Uriz, Juan Roberto Rodriguez-Madoz, Leonor Puchades-Carrasco, Caroline A Heckman, Paula Rodriguez-Otero, Francisco J Planes, Xabier Agirre, Felipe Prósper
Published in
Blood cancer journal. Volume 16. Issue 1. Aug 11, 2026. Epub Aug 11, 2026.
Abstract
Aberrant metabolism, a hallmark of cancer, reveals vulnerabilities across human tumors. Here, we demonstrate that transcriptomic alterations of metabolism-related genes (metabolic transcriptome) in multiple myeloma (MM), classify patients into six metabolic-transcriptional groups characterized by specific metabolic pathways and cytogenetic alterations, independent of currently described myeloma risk groups. Interestingly, hyperdiploid patients clustered into 2 groups (MM5 and MM6) with significantly distinct Progression-Free and Overall Survival. The MM5 group, with worse prognosis, showed a significant enrichment in myeloid and dormant cell signatures. Regulon analysis identified myeloid transcription factors (TFs) as regulators of metabolic, myeloid, and dormant genes in MM5. In addition to myeloid genes acting as potential biomarkers and therapeutic targets, the metabolic gene ACSL1 plays a crucial role in MM5, decreasing cell proliferation by affecting metabolism and mitochondrial function, sensitizing MM to BCL-2 family inhibitors. These findings highlight ACSL1 as a promising therapeutic target for MM5 and provide new insights into MM metabolic heterogeneity that may guide future precision medicine strategies.
PMID:
42827144
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.
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