Novel Investigational Agents and Pathways That May Influence the Future Management of Acute Myeloid Leukemia

Premnath, Naveen; Madanat, Yazan F.

doi:10.3390/cancers15112958

Cited by 2 publications

(2 citation statements)

References 112 publications

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“…Several early-phase clinical trials are investigating the safety and efficacy of menin inhibitors in AML with KMT2Ar or NPM1mut AML. Very encouraging safety and efficacy data are currently available from studies of two menin inhibitors: SNDX-5613 (revumenib) and KO-539 (ziftomenib) [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Ongoing phase I/II clinical trials evaluating menin inhibitor therapy are listed in Table 1 .…”

Section: Menin Inhibitors: Ongoing Clinical Trials In Amlmentioning

confidence: 99%

“…The AUGMENT-101 trial ( NCT04065399 ) is a first-in-human phase (Ph) 1 study to determine the safety, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and pharmacokinetic (PK) profile of revumenib in patients with relapsed or refractory (R/R) acute leukemia [ 22 , 23 , 24 , 25 ]. Patients enrolled in this trial are heavily pretreated and have a very poor prognosis.…”

Section: Menin Inhibitors: Ongoing Clinical Trials In Amlmentioning

confidence: 99%

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A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia

Candoni,

Coppola

2024

Hematology Reports

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Menin inhibitors are new and promising agents currently in clinical development that target the HOX/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A-rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemias. The mechanism of action of this new class of agents is based on the disruption of the menin–KMT2A complex (consisting of chromatin remodeling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or with mutated NPM1. To date, this new class of drugs has been tested in phase I and II clinical trials, both alone and in combination with synergistic drugs showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this brief review, we summarize the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data on the treatment of acute myeloid leukemia with this promising new class of agents, particularly revumenib and ziftomenib.

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Section: Menin Inhibitors: Ongoing Clinical Trials In Amlmentioning

confidence: 99%

Section: Menin Inhibitors: Ongoing Clinical Trials In Amlmentioning

confidence: 99%

A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia

Candoni,

Coppola

2024

Hematology Reports

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Landscape of internal N7-methylguanosine of long non-coding RNA modifications in resistant acute myeloid leukemia

Han,

Liu,

Zhou

et al. 2023

BMC Genomics

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Background Growing evidence indicates that RNA methylation plays a fundamental role in epigenetic regulation, which is associated with the tumorigenesis and drug resistance. Among them, acute myeloid leukemia (AML), as the top acute leukemia for adults, is a deadly disease threatening human health. Although N7-methylguanosine (m7G) has been identified as an important regulatory modification, its distribution has still remained elusive. Methods The present study aimed to explore the long non-coding RNA (lncRNA) functional profile of m7G in AML and drug-resistant AML cells. The transcriptome-wide m7G methylation of lncRNA was analyzed in AML and drug-resistant AML cells. RNA MeRIP-seq was performed to identify m7G peaks on lncRNA and differences in m7G distribution between AML and drug-resistant AML cells. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to predict the possible roles and m7G-associated pathway. Results Using m7G peak sequencing, it was found that a sequence motif was necessary for m7G methylation in drug-resistant AML lncRNA. Unsupervised hierarchical cluster analysis confirmed that lncRNA m7G methylation occurred more frequently in drug-resistant AML cells than in AML cells. RNA sequencing demonstrated that more genes were upregulated by methylation in drug-resistant AML cells, while methylation downregulated more genes in AML cells. The GO and KEGG pathway enrichment analyses revealed that genes having a significant correlation with m7G sites in lncRNA were involved in drug-resistant AML signaling pathways. Conclusion Significant differences in the levels and patterns of m7G methylation between drug-resistant AML cells and AML cells were revealed. Furthermore, the cellular functions potentially influenced by m7G in drug-resistant AML cells were predicted, providing evidence implicating m7G-mediated lncRNA epigenetic regulation in the progression of drug resistance in AML. These findings highlight the involvement of m7G in the development of drug resistance in AML.

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Novel Investigational Agents and Pathways That May Influence the Future Management of Acute Myeloid Leukemia

Cited by 2 publications

References 112 publications

A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia

A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia

Landscape of internal N7-methylguanosine of long non-coding RNA modifications in resistant acute myeloid leukemia

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