ArticleCancer & metabolism2025
Lactate metabolism in clonal plasma cells and its therapeutic implications in multiple myeloma patients with elevated serum LDH levels.
Article in Cancer & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Repurposing Syrosingopine for Cancer Therapy: Lactate Trapping and ISR Sensitization as Metabolic Vulnerabilities.Oncology and therapy · 2026Review
- Solute carrier transporters as metabolic gatekeepers in tumor-microenvironment crosstalk.Acta pharmacologica Sinica · 2026Review
- The regulatory roles and therapeutic strategies of the solute carrier transporters in cancer metabolism.NPJ precision oncology · 2026Review
- Impact of t(11;14) primary cytogenetic abnormality and the cumulative effect of multiple high-risk cytogenetics at diagnosis on the outcomes of patients with primary plasma cell leukemia.Blood cancer journal · 2025Article
- LDHAL6B is a novel prognostic marker and promotes disease progression in multiple myeloma.Haematologica · 2025Article
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Authors and funding
15 authors.
Funding
Abstract
introductionThis study aimed to evaluate the metabolic differences between MM cells derived from patients with elevated serum LDH levels and those without elevated serum LDH levels to identify biological differences that could be exploited for therapeutic purposes.
methodsWe performed transcriptome assessments of CD138 + MM cells derived from patients with elevated serum LDH levels compared to those without elevated serum LDH levels and validated the findings in a larger public dataset. Functional metabolic assessments of our findings were performed using a combination of stable isotope resolved metabolomics (SIRM), bioenergetic flux measurement assays, and live cell analysis in human myeloma cell lines and primary MM patient cells.
resultsWe identified SLC16A1, responsible for the formation of MCT1, a well-defined bi-directional transporter of lactate in and out of a cell with a predilection to importing extracellular lactate, as differentially expressed between the two groups. This finding was functionally confirmed by higher membranous MCT1 protein expression and SIRM on MM cells derived from patients with elevated serum LDH levels compared to those without elevated serum LDH levels. Finally, disrupting lactate transport in and out of CD138 + MM cells was maximally achievable only with dual inhibition of MCT1 and its partner, MCT4, which was preferentially more cytotoxic in MM cells derived from patients with elevated serum levels of LDH.
conclusionMCT1 mRNA and protein expression distinguish MM cells derived from patients with elevated serum LDH levels from those without elevated serum LDH levels. However, only dual inhibition of MCT1 and MCT4 can disrupt lactate transport in multiple myeloma (MM) cells, with preferential cytotoxicity in MM cells from patients with high serum LDH levels.
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