Effect of &lt;i&gt;L&lt;/i&gt;-Asparaginase Combined with Vincristine and Prednisolone on Acute Myeloblastic Leukemia (M0) Associated with Non-Hodgkin Lymphoma

Horikoshi, Akira; Takei, Kazuhiro; Iriyama, Noriyoshi; Uenogawa, Kumi; Ishizuka, Hikaru; Shiraiwa, Hidetaka; Hosokawa, Yoshifumi; Sawada, Shigemasa; Kitoh, Toshiyuki

doi:10.1159/000243725

Cited by 5 publications

(3 citation statements)

References 45 publications

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“…A more complete attempt to categorize AML subgroups on the basis of ASNase sensitivity indicated that M1 and M0 were the most sensitive, while M3 and M7 were poorly sensitive and M4-M5 were confirmed to have a moderate sensitivity (35). Although no correlation was made between ASNase sensitivity and ASNS protein expression in that paper, a good response to therapy associated with low ASNS mRNA expression was later reported, at least for M0 (36). More recently, since chromosome 7 monosomy (-7) is frequently detected in adverse-risk AML and therapy-related myeloid neoplasms in children, the hypothesis that this aberration correlates with sensitivity to ASNase was investigated (37).…”

Section: Low Expression Of Asns As a Marker Of Sensitivity To Asnase mentioning

confidence: 95%

Asparagine Synthetase in Cancer: Beyond Acute Lymphoblastic Leukemia

et al. 2020

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Asparagine Synthetase (ASNS) catalyzes the synthesis of the non-essential amino acid asparagine (Asn) from aspartate (Asp) and glutamine (Gln). ASNS expression is highly regulated at the transcriptional level, being induced by both the Amino Acid Response (AAR) and the Unfolded Protein Response (UPR) pathways. Lack of ASNS protein expression is a hallmark of Acute Lymphoblastic Leukemia (ALL) blasts, which, therefore, are auxotrophic for Asn. This peculiarity is the rationale for the use of bacterial L-Asparaginase (ASNase) for ALL therapy, the first example of anti-cancer treatment targeting a tumor-specific metabolic feature. Other hematological and solid cancers express low levels of ASNS and, therefore, should also be Asn auxotrophs and ASNase sensitive. Conversely, in the last few years, several reports indicate that in some cancer types ASNS is overexpressed, promoting cell proliferation, chemoresistance, and a metastatic behavior. However, enhanced ASNS activity may constitute a metabolic vulnerability in selected cancer models, suggesting a variable and tumor-specific role of the enzyme in cancer. Recent evidence indicates that, beyond its canonical role in protein synthesis, Asn may have additional regulatory functions. These observations prompt a re-appreciation of ASNS activity in the biology of normal and cancer tissues, with particular attention to the fueling of Asn exchange between cancer cells and the tumor microenvironment.

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Section: Low Expression Of Asns As a Marker Of Sensitivity To Asnase mentioning

confidence: 95%

Asparagine Synthetase in Cancer: Beyond Acute Lymphoblastic Leukemia

et al. 2020

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“…Generally, asparaginase may be beneficial for malignancies expressing low or no ASNS activity (68,70,73,74), and several studies have investigated the use of asparaginase in non-hematologic malignancies, such as pancreatic, ovarian, and breast cancers (75)(76)(77)(78)(79). Furthermore, there is substantial clinical evidence that including asparaginase during the treatment of AML results in better treatment outcomes (80)(81)(82)(83)(84)(85)(86)(87). While few studies in CML patients are available to assess the clinical efficacy of asparaginase (88)(89)(90)(91), preclinical studies indicate that asparaginase may also be beneficial for CML treatment (92,93).…”

Section: There Is Strong Clinical Evidence Supporting Vulnerabilities To Aspartate-derived Neaas In Leukemiasmentioning

confidence: 99%

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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“…Vincristine (VCR) is a widely used chemotherapeutic agent for the treatment of acute leukemia and solid tumors, but not acute myeloid leukaemia (132). It has been hypothesized that resistance of myeloblasts to VCR is related to MPO and production of HOCl.…”

Section: Taurinementioning

confidence: 99%

Sulphur-containing non enzymatic antioxidants therapeutic tools against cancer

Matés¹

2012

Front Biosci

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The prevention of oxidation is an essential process in all cells, as decreased antioxidant protection may lead to cytotoxicity, mutagenicity and carcinogenicity. The mechanisms by which oxidative stress contributes to carcinogenesis include modulation of gene expression and induction of genetic modifications. Cellular methylation and antioxidant metabolism are linked by the transsulfuration pathway, which converts the methionine cycle intermediate, homocysteine, to cysteine, the limiting reagent in glutathione synthesis. Taurine can protect cells from oxidant-induced injury scavenging strong oxidant and cytotoxic agents, and lipoic acid can regenerate glutathione. N-acetylcysteine has anticancer properties such as counteractions against mutagens and prevention of tumor progression. The oxidizing agents react with the thiol group of these non enzymatic antioxidants determining cellular redox potential, and modulating several biological events, since different redox-sensitive molecules are involved in many cell responses such as proliferation, growth arrest, and death. The high metabolic activity characteristic of cancer cells often upregulates oxidative stress protection mechanisms. In fact, glutathione depletion is an early hallmark observed in apoptosis and it has been demonstrated as a common feature of cancer.

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Effect of <i>L</i>-Asparaginase Combined with Vincristine and Prednisolone on Acute Myeloblastic Leukemia (M0) Associated with Non-Hodgkin Lymphoma

Cited by 5 publications

References 45 publications

Asparagine Synthetase in Cancer: Beyond Acute Lymphoblastic Leukemia

Asparagine Synthetase in Cancer: Beyond Acute Lymphoblastic Leukemia

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

Sulphur-containing non enzymatic antioxidants therapeutic tools against cancer

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