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Gonsalves WI, Jang JS, Jessen E, et al. In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells. Cancer Metab. 2020;8(1):29doi: 10.1186/s40170-020-00235-4.
Gonsalves, W. I., Jang, J. S., Jessen, E., Hitosugi, T., Evans, L. A., Jevremovic, D., Pettersson, X. M., Bush, A. G., Gransee, J., Anderson, E. I., Kumar, S. K., & Nair, K. S. (2020). In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells. Cancer & metabolism, 8(1), 29. https://doi.org/10.1186/s40170-020-00235-4
Gonsalves, Wilson I, et al. "In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells." Cancer & metabolism vol. 8,1 (2020): 29. doi: https://doi.org/10.1186/s40170-020-00235-4
Gonsalves WI, Jang JS, Jessen E, Hitosugi T, Evans LA, Jevremovic D, Pettersson XM, Bush AG, Gransee J, Anderson EI, Kumar SK, Nair KS. In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells. Cancer Metab. 2020 Dec 11;8(1):29. doi: 10.1186/s40170-020-00235-4. PMID: 33308307; PMCID: PMC7731537.
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Cancer Metab. 2020 Dec 11;8(1):29. doi: 10.1186/s40170-020-00235-4.

In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells.

Cancer & metabolism

Wilson I Gonsalves, Jin Sung Jang, Erik Jessen, Taro Hitosugi, Laura A Evans, Dragan Jevremovic, Xuan-Mai Pettersson, Alexander Graham Bush, Jaimee Gransee, Emilie I Anderson, Shaji K Kumar, K Sreekumaran Nair

Affiliations

  1. Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. [email protected].
  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  3. Department of Health Service Research, Mayo Clinic, Rochester, MN, USA.
  4. Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  5. Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
  6. Mayo Clinic Metabolomics Core, Mayo Clinic, Rochester, MN, USA.
  7. Division of Endocrinology, Mayo Clinic, Rochester, MN, USA.

PMID: 33308307 PMCID: PMC7731537 DOI: 10.1186/s40170-020-00235-4

Abstract

BACKGROUND: Overexpression of c-Myc is required for the progression of pre-malignant plasma cells in monoclonal gammopathy of undetermined significance (MGUS) to malignant plasma cells in multiple myeloma (MM). c-Myc also increases glutamine anaplerosis into the tricarboxylic acid (TCA) cycle within cancer cells. Whether increased glutamine anaplerosis is associated with the progression of pre-malignant to malignant plasma cells is unknown.

METHODS: Human volunteers (N = 7) and patients with MGUS (N = 11) and MM (N = 12) were prospectively recruited to undergo an intravenous infusion of

RESULTS: Despite notable heterogeneity, stable isotope-resolved metabolomics (SIRM) revealed that the mean

CONCLUSION: Measurement of the in vivo activity of glutamine anaplerosis into the TCA cycle provides novel insight into the metabolic changes associated with the transformation of pre-malignant plasma cells in MGUS to malignant plasma cells in MM.

TRIAL REGISTRATION: NCT03384108 and NCT03119883.

Keywords: Glutamine; Myeloma; Plasma cell malignancies; Stable isotope metabolomics

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