Novel therapies for AML: a round-up for clinicians

Swaminathan, Mahesh; Wang, Eunice S.

doi:10.1080/17512433.2020.1850255

Cited by 27 publications

(21 citation statements)

References 58 publications

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“…While using Decitabine, this study also used inhibitors of other mechanisms. Azacitidine (5-Azacytidine, 5-AzaC, Ladakamycin, AZA, 5-Aza, CC-486) is a nucleoside analog of cytidine, which inhibits DNA methylation by binding to DNA methyltransferase in competition with cytidine (75)(76)(77)(78). Our results show that Azacitidine can also down-regulate the promoter methylation rate of miR-338-5p, but the activity of Decitabine is better than that of Azacitidine (that is, the inhibitory activity of Decitabine is higher than that of Azacitidine at the same concentration).…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

et al. 2021

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The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.

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Section: Discussionmentioning

confidence: 99%

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

et al. 2021

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“…Gemtuzumab ozogamicin (GO) is the only antibody-drug conjugate approved by both the Food and Drug Administration (in 2020) and European Medicines Agency in newly diagnosed and refractory CD33-positive AML for patients aged 1 month or older. A combination of anti-CD33 IG4 and calicheamicin as the cytotoxic agent GO has been shown to improve event-free survival, though not the overall survival, when used with the standard chemotherapy [59]. In the ALFA-0701 trial, assessing the safety and efficacy of GO, patients aged 50-70 years old with de novo AML were given Gemtuzumab ozogamicin in addition to the standard induction chemotherapy; the control group consisted of patients given only the standard chemotherapy.…”

Section: Immunotherapy 231 Drug-antibody Conjugatesmentioning

confidence: 99%

Molecular-Targeted Therapy of Pediatric Acute Myeloid Leukemia

et al. 2022

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Acute myeloid leukemia (AML) accounts for approximately 15–20% of all childhood leukemia cases. The overall survival of children with acute myeloid leukemia does not exceed 82%, and the 5-year event-free survival rates range from 46% to 69%. Such suboptimal outcomes are the result of numerous mutations and epigenetic changes occurring in this disease that adversely affect the susceptibility to treatment and relapse rate. We describe various molecular-targeted therapies that have been developed in recent years to meet these challenges and were or are currently being studied in clinical trials. First introduced in adult AML, novel forms of treatment are slowly beginning to change the therapeutic approach to pediatric AML. Despite promising results of clinical trials investigating new drugs, further clinical studies involving greater numbers of pediatric patients are still needed to improve the outcomes in childhood AML.

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“…The clinical role of antibody-based therapy currently approved for AML treatment is limited to antibody-drug conjugates (ADCs), wherein an innate immune response is elicited towards a myeloid-specific antigen, such as CD33-binding gemtuzumab ozogamicin [ 5 , 48 , 49 ]. However, several antibody-based therapies aimed at inducing a cell-mediated cytotoxic response against leukemic cells are being investigated for AML therapy.…”

Section: T Cell Immunotherapymentioning

confidence: 99%

“…Despite numerous studies aimed at harnessing the power of the natural immunologic antileukemic response, there has been no significant advancement made in the standard treatment regimen in over 50 years [ 3 ]. Current treatment consists of a high-intensity induction phase wherein cytotoxic chemotherapy, commonly the “7+3 regimen” of cytarabine plus anthracycline, or other target-specific agents are administered based on disease profile as well as patient risk and comorbidities [ 3 , 4 , 5 ]. Complete remission (CR) may be attained in approximately 70–80% of patients < 60 years of age or in 50% of patients 60 or older [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of T Cell Immunotherapy in Acute Myeloid Leukemia

Hao

Sholy

Wang

et al. 2021

Cells

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Acute myeloid leukemia (AML) is a heterogeneous disease associated with various alterations in T cell phenotype and function leading to an abnormal cell population, ultimately leading to immune exhaustion. However, restoration of T cell function allows for the execution of cytotoxic mechanisms against leukemic cells in AML patients. Therefore, long-term disease control, which requires multiple therapeutic approaches, includes those aimed at the re-establishment of cytotoxic T cell activity. AML treatments that harness the power of T lymphocytes against tumor cells have rapidly evolved over the last 3 to 5 years through various stages of preclinical and clinical development. These include tissue-infiltrated lymphocytes (TILs), bispecific antibodies, immune checkpoint inhibitors (ICIs), chimeric antigen receptor T (CAR-T) cell therapy, and tumor-specific T cell receptor gene-transduced T (TCR-T) cells. In this review, these T cell-based immunotherapies and the potential of TILs as a novel antileukemic therapy will be discussed.

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Novel therapies for AML: a round-up for clinicians

Cited by 27 publications

References 58 publications

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

Molecular-Targeted Therapy of Pediatric Acute Myeloid Leukemia

The Role of T Cell Immunotherapy in Acute Myeloid Leukemia

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