Metabolomic profiling identifies pathways associated with minimal residual disease in childhood acute lymphoblastic leukaemia

Schraw, Jeremy M.; Junco, Jacob J.; Brown, Austin L.; Scheurer, Michael E.; Rabin, Karen R.; Lupo, Philip J.

doi:10.1016/j.ebiom.2019.09.033

Cited by 23 publications

(28 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many diseases have changes in central carbon metabolism, including cancer, diabetes, and heart disease (Walsby-Tickle et al, 2020 ). Schraw et al ( 2019 ) showed that changes in central carbon metabolism and amino acid metabolism were related to minimal residual disease (MRD) positivity and that metabonomics has potential utility in the risk prediction and targeted treatment of pediatric acute lymphoblastic leukemia (ALL). In HNSCC, cisplatin-induced oxidative stress triggers rapid changes in carbon flux in central carbon metabolism, which can provide potentially useful information for predicting treatment response (Yu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

et al. 2021

View full text Add to dashboard Cite

Background: Glycolysis is critical in the occurrence and development of tumors. Owing to the biological and clinical heterogeneity of patients with BRCA, the traditional predictive classification system is far from satisfactory. Survival and prognosis biomarkers related to glycolysis have broad application prospects for assessing the risk of patients and guiding their individualized treatment.Methods: The mRNA expression profiles and clinical information of patients with BRCA were obtained from TCGA database, and glycolysis-related genes were obtained by GSEA. Patients with BRCA were randomly divided into the training cohort and testing cohort. Univariate and multivariate Cox analyses were used to establish and validate a new mRNA signature for predicting the prognosis of patients with BRCA.Results: We established a four-gene breast cancer prediction signature that included PGK1, SDHC, PFKL, and NUP43. The patients with BRCA in the training cohort and testing cohort were divided into high-risk and low-risk groups based on the signature. The AUC values were 0.74 (training cohort), 0.806 (testing cohort) and 0.769 (entire cohort), thereby showing that the prediction performance of the signature is acceptable. Additionally, Cox regression analysis revealed that four-gene signature could independently predict the prognosis of BRCA patients without being affected by clinical factors.Conclusion: We constructed a four-gene signature to predict the prognosis of patients with BRCA. This signature will aid in the early diagnosis and personalized treatment of breast cancer, but the specific associated biological mechanism requires further study.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Such approaches depend on the knowledge of potential therapeutic targets in relapsed AML cells. [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles

Aasebø

Berven

Hovland

et al. 2020

Cancers

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of the patients who receive the most intensive treatment develop chemoresistant leukemia relapse. Although the leukemogenic events leading to relapse seem to differ between patients (i.e., regrowth from a clone detected at first diagnosis, progression from the original leukemic or preleukemic stem cells), a common characteristic of relapsed AML is increased chemoresistance. The aim of the present study was to investigate at the proteomic level whether leukemic cells from relapsed patients present overlapping molecular mechanisms that contribute to this chemoresistance. We used liquid chromatography–tandem mass spectrometry (LC–MS/MS) to compare the proteomic and phosphoproteomic profiles of AML cells derived from seven patients at the time of first diagnosis and at first relapse. At the time of first relapse, AML cells were characterized by increased levels of proteins important for various mitochondrial functions, such as mitochondrial ribosomal subunit proteins (MRPL21, MRPS37) and proteins for RNA processing (DHX37, RNA helicase; RPP40, ribonuclease P component), DNA repair (ERCC3, DNA repair factor IIH helicase; GTF2F1, general transcription factor), and cyclin-dependent kinase (CDK) activity. The levels of several cytoskeletal proteins (MYH14/MYL6/MYL12A, myosin chains; VCL, vinculin) as well as of proteins involved in vesicular trafficking/secretion and cell adhesion (ITGAX, integrin alpha-X; CD36, platelet glycoprotein 4; SLC2A3, solute carrier family 2) were decreased in relapsed cells. Our study introduces new targetable proteins that might direct therapeutic strategies to decrease chemoresistance in relapsed AML.

show abstract

“…cALL cells exhibit alterations in glycolysis, TCA cycle, and pentose pathways as demonstrated by a recent study analyzing 155 patient samples using mass spectrometry metabolomics 88 . Schraw et al.…”

Section: Cell Metabolism In Callmentioning

confidence: 99%

“…found that these metabolite changes were enriched in end‐induction MRD‐positive patients. Inhibition of a rate‐limiting NAD+ generating enzyme in glycolysis, three nicotinamide phosphoribosyltransferase, reduces cell viability in B‐ and T‐ALL cell lines, patient samples, and PDXs highlighting metabolic vulnerabilities for therapeutic targeting in cALL 88 …”

Section: Cell Metabolism In Callmentioning

confidence: 99%

Metabolic reprogramming in childhood acute lymphoblastic leukemia

Sbirkov

Burnusuzov

Sarafian

2020

Pediatric Blood & Cancer

View full text Add to dashboard Cite

The first observations of altered metabolism in malignant cells were made nearly 100 years ago and therapeutic strategies targeting cell metabolism have been in clinical use for several decades. In this review, we summarize our current understanding of cell metabolism dysregulation in childhood acute lymphoblastic leukemia (cALL). Reprogramming of cellular bioenergetic processes can be expected in the three distinct stages of cALL: at diagnosis, during standard chemotherapy, and in cases of relapse. Upregulation of glycolysis, dependency on anaplerotic energy sources, and activation of the electron transport chain have all been observed in cALL.While the current treatment strategies are tackling some of these aberrations, cALL cells are likely to be able to rewire their metabolism in order to escape therapy, which may contribute to a refractory disease and relapse. Finally, here we focus on novel therapeutic approaches emerging from our evolving understanding of the alterations of different metabolic networks in lymphoblasts. K E Y W O R D SBioenergetics, cALL, cell metabolism, therapy

show abstract

Metabolomic profiling identifies pathways associated with minimal residual disease in childhood acute lymphoblastic leukaemia

Cited by 23 publications

References 34 publications

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles

Metabolic reprogramming in childhood acute lymphoblastic leukemia

Contact Info

Product

Resources

About