Amino acid metabolism of myeloma cells in culture

Roberts, R.S.; Hsu, H.W.; Lin, Kuei-Tang; Yang, Tao

doi:10.1242/jcs.21.3.609

Cited by 32 publications

(2 citation statements)

References 7 publications

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“…Generally, MM cells are characterized by an increased metabolism of glucose, glutamine, fatty acids, and nucleotides, principally mediated by the activation of specific oncogenes [44]. In addition, in vitro, the MM cells growth is strictly bounded by the depletion of glutamine, suggesting that glutamminolysis has a key role in the complex metabolism of these cells [45,46]. At the same time, it has been demonstrated that MM patients show significantly lower serum glutamine if compared to healthy controls [47], and recent data point out that the altered glutamine metabolism activated by glutamminolysis [48][49][50] seems to be a metabolic consequence of recurrent chromosomal aberrations observed in MM.…”

Section: Glutamminolysis and Hyperammonemiamentioning

confidence: 99%

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations

Carlisi

Mancuso

Presti

et al. 2022

Cancers

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The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in the 8% of multiple myeloma patients, and it may be caused by artero-venous shunts, enhanced angiogenesis, glutamminolysis, hyperammonemia and hemorheological alterations with increase in plasma viscosity. The high output heart failure in multiple myeloma is associated with significant morbidity and mortality, emphasizing the need for a multidisciplinary approach.

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Section: Glutamminolysis and Hyperammonemiamentioning

confidence: 99%

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations

Carlisi

Mancuso

Presti

et al. 2022

Cancers

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show abstract

“…It has also been reported that human myeloma cell lines (HMCLs) are highly sensitive to Gln depletion and MM cells are also addictive to Gln ( 17 ). There are studied reported that MM cells are highly reliant on glutamine metabolism ( 18 , 19 ). It was found that continued cell survival in the absence of glutamine maintained the expression of myeloid leukemia factor 1, but importantly induced the expression of pro-apoptotic BIM expression ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

The potential of glutamine metabolism-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in multiple myeloma patients

Zhong¹,

Xu²,

Liu³

2022

Ann Transl Med

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Background: Glutamine (Gln) metabolism has been confirmed as an important fuel in cancer metabolism.This study aimed to uncover potential links of Gln with long non-coding RNAs (lncRNAs) and the prognostic value of Gln-associated lncRNAs in multiple myeloma (MM) patients. Methods: The RNA-seq expression profile and corresponding clinical data of gastric cancer obtained from Gene Expression Omnibus (GEO) database. Unsupervised consensus clustering was used to cluster MM samples based on Gln-associated lncRNAs. The overall survival (OS), biological pathways, and immune microenvironment were compared in different subtypes. Differential analysis was utilized to identify differentially expressed lncRNAs (DElncRNAs) in different subtypes. A risk model was constructed based on DElncRNAs by using Cox regression, least absolute shrinkage and selection operator (LASSO), and the stepAIC algorithm. Results: We screened 50 Gln-associated lncRNAs and identified 3 molecular subtypes (clust1, clust2, and clust3) based on lncRNA expression profiles. Clust3 subtype showed the worst prognosis and highest enrichment of Gln metabolism pathway. Angiogenesis, epithelial-mesenchymal transition (EMT), and cell cycle-related pathways were relatively activated in clust3. Then, we identified 11 prognostic DElncRNAs for constructing the risk model. The MM samples were divided into high-and low-risk groups with distinct prognosis according to the risk score. The risk score was significantly associated with cell cycle and infiltration of many immune cells. Conclusions: This study characterized the role of Gln-associated lncRNAs in Gln metabolism contributing for tumor-related pathways and immune microenvironment in MM patients. The 11 lncRNAs in the risk model may serve as potential targets for exploring the mechanism of Gln metabolism or serve as potential biomarkers for MM prognosis.

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Cell susceptibility to apoptosis by glutamine deprivation and rescue: Survival and apoptotic death in cultured lymphoma-leukemia cell lines

et al. 1996

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Human leukemia/lymphoma cells maintained in culture medium without provision of fresh nutrients lose viability and die by a process resembling apoptosis within a few days. Upon incubation in an FCS-supplemented RPMI 1640 medium containing 2 mM L-glutamine CEM, Namalwa, HL-60 and U937 cells, seeded at initial densities of 0.2 to 1 x 10(6) cells/ml, ceased growing within 3-5 days and progressively entered an apoptotic pathway, as assessed by nucleosomal DNA fragmentation and morphology. Both the major energy-source nutrients in the medium, glucose and glutamine, became rapidly exhausted during the incubation. Further studies were performed using CEM cells. Incubation in glutamine-free or glucose-free medium renewed every 24 h showed that glutamine deprivation is associated with cell death by apoptosis independent of energetic failure, whereas glucose deprivation is followed by rapid loss of mitochondrial function with sharp drop of intracellular ATP and cell death by necrosis. A 12-24 h incubation in glutamine-depleted medium was required to direct the cells toward the apoptotic pathway. Growth arrest followed by apoptotic death was detected in CEM cells when medium glutamine concentration remained below 0.3-0.4 mM for at least 24 h, but a reinstatement of medium glutamine to 2 mM within this period rescued the cells from growth arrest and death.

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Amino acid metabolism of myeloma cells in culture

Cited by 32 publications

References 7 publications

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations

The potential of glutamine metabolism-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in multiple myeloma patients

Cell susceptibility to apoptosis by glutamine deprivation and rescue: Survival and apoptotic death in cultured lymphoma-leukemia cell lines

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