Serine Requirement in Leukemic and Normal Blood Cells

Regan, James D.; Vodopick, H.; Takeda, Susumu; Lee, William H.; Faulcon, Frederick M.

doi:10.1126/science.163.3874.1452

Cited by 36 publications

(11 citation statements)

References 6 publications

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“…For CML, similar to our analysis, several studies have shown that levels of glutamate, serine, which is a precursor of cysteine, and alanine are increased by CML (153)(154)(155). Consistent with these NEAAs playing an important role in CML, restriction of serine (156,157) and its derivatives glycine (156), or cysteine (158,159) decreases CML proliferation, supporting that targeting these NEAA pathways may be a potential target for CML.…”

Section: Restriction Of Other Neaas Derived From Glutamate Decrease Myeloid Leukemia Proliferationsupporting

confidence: 88%

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

et al. 2021

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Amino acid (AA) metabolism plays an important role in many cellular processes including energy production, immune function, and purine and pyrimidine synthesis. Cancer cells therefore require increased AA uptake and undergo metabolic reprogramming to satisfy the energy demand associated with their rapid proliferation. Like many other cancers, myeloid leukemias are vulnerable to specific therapeutic strategies targeting metabolic dependencies. Herein, our review provides a comprehensive overview and TCGA data analysis of biosynthetic enzymes required for non-essential AA synthesis and their dysregulation in myeloid leukemias. Furthermore, we discuss the role of the general control nonderepressible 2 (GCN2) and-mammalian target of rapamycin (mTOR) pathways of AA sensing on metabolic vulnerability and drug resistance.

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Section: Restriction Of Other Neaas Derived From Glutamate Decrease Myeloid Leukemia Proliferationsupporting

confidence: 88%

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

et al. 2021

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“…Serine levels were increased significantly ( p adj 9.9 × 10 −5 ) in the pellets of leukemia cells, whereas the opposite ( p adj 2.5 × 10 −9 ) was observed in the corresponding supernatants. Since serine is an essential amino acid for leukemic cells , this might explain our findings of increased serine uptake and subsequent conversion to glycine.…”

Section: Resultsmentioning

confidence: 79%

Distinct metabolic differences between various human cancer and primary cells

et al. 2013

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Recent years have seen resurging interest in cancer cell metabolism and the role of secreted cancer metabolites in modulating the tumor stroma. Using a combination of nontargeted and targeted LC and GC-MS methods, the exometabolomes of three leukemia, two melanoma, three renal cell carcinoma, two colorectal adenocarcinoma, four hepatocellular carcinoma, three breast cancer, two bladder carcinoma, and one glioblastoma cell line, as well as five primary cultures of human melanocytes, hepatocytes, monocytes, CD4 and CD8 lymphocytes, that had been all cultivated under identical conditions, were investigated. Unsupervised affinity propagation clustering of the metabolic footprints yielded five distinct clusters that grouped the investigated cell cultures mainly according to the tissue of origin. A common expected feature of all neoplastic cells was high lactate production. Extracellular arginine and nicotinamide were major discriminants between normal and neoplastic hepatocytes. Further, significant differences in the assimilation of di- and tripeptides were observed. This finding appears to underscore the importance of peptides for meeting the increased bioenergetic and biosynthetic demands of many cancers.

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“…Of the amino acids regarded as nutrition ally nonessential, L-serine has been report ed to be required for optimal growth of rab bit fibroblasts [Hajj and Swim, 1956], hu man chronic granulocytic leukemia cells and normal human bone marrow cells [Regan et al, 1969]. Monkey kidney cells require gly cine [Eagle et al, 1958] and both glycine and L-serine are required for optimal growth of Novikoff hepatoma cells [McCoy et al, 1959] and Walker carcinosarcoma 256 cells [McCoy et al, 1956].…”

Section: Discussionmentioning

confidence: 99%

<i>L</i>-Alanine – an Essential Amino Acid for Growth of Lymphocytes <i>in vitro</i>

Nordlind¹,

Ernström²,

Mutt³

1979

Int Arch Allergy Immunol

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A factor in ultraftitrated (UM 10) extracts of calf thymus, liver and spleen stimulated the uptake of ³H-thymidine in DNA of cultured lymphocytes. The factor was purified by ion-exchange chromatography and gel chromatography and identified as alanine, which is lacking in the culture medium, RPMI 1640. An optimal amount of L-alanine increased the uptake of ³H-thymidine in DNA of lymphocytes from different species by about 100%. L-alanine should be regarded as a growth factor for lymphocytes in vitro and should be added to RPMI 1640, when this tissue culture medium is used for lymphocytes.

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Serine Requirement in Leukemic and Normal Blood Cells

Cited by 36 publications

References 6 publications

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

Distinct metabolic differences between various human cancer and primary cells

<i>L</i>-Alanine – an Essential Amino Acid for Growth of Lymphocytes <i>in vitro</i>

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