Clinical and molecular consequences of fusion genes in myeloid malignancies

Matsukawa, Toshihiro; Aplan, Peter D.

doi:10.1002/stem.3263

Cited by 13 publications

(10 citation statements)

References 92 publications

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“…Cloning translocation breakpoints have given important insights into the pathogenesis of this disorder. Mutations in transcription factor genes involved in normal hematopoietic production are among the chromosomal aberrations seen in acute myeloid leukemia [ 4 ]. Mutations affecting transcription factors and key cell genes result in uncontrolled proliferation and compromised differentiation [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds

et al. 2021

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Leukemia is a group of hematological neoplastic disorders linked to high mortality rates worldwide, but increasing resistance has led to the therapeutic failure of conventional chemotherapy. This study aimed to evaluate in vitro the antileukemic activity and potential mechanism of action of a polyphenolic extract obtained from the seeds of Coriandrum sativum L. (CSP). A methylthiazoletetrazolium assay was performed to assess the CSP cytotoxicity on chronic (K562) and acute (HL60) myeloid leukemia cell lines and on normal Vero cell line. CSP toxicity was also evaluated in vivo using the OECD 423 acute toxicity model on Swiss albino mice. The results demonstrated a remarkable antitumoral activity against K562 and HL60 cell lines (IC50 = 16.86 µM and 11.75 µM, respectively) although no cytotoxicity was observed for the Vero cells or mice. A silico study was performed on the following receptors that are highly implicated in the development of leukemia: ABL kinase, ABL1, BCL2, and FLT3. The molecular docking demonstrated a high affinity interaction between the principal CSP components and the receptors. Our findings demonstrated that CSP extract has remarkable antileukemic activity, which is mainly mediated by the flavonoids, catechins, and rutin, all of which showed the highest binding affinity for the targeted receptors. This study revealed a promising active compound alternative research-oriented biopharmacists to explore.

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Section: Introductionmentioning

confidence: 99%

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds

et al. 2021

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“…Effects unique to SVs are gene fusions, gene deletions, gene duplications, and genome rearrangements. Gene fusions are cases where a SV causes parts of two genes to end up back-to-back, resulting in the formation of a hybrid gene which may alter considerably fundamental cellular processes, such as proliferation, self-renewal, and differentiation of the cell, which properties are playing key roles in cancer [19]. The deletion or duplication of genes or their regulatory elements can have a large impact on the production of RNA and, in turn, that of the final protein products.…”

Section: Structural Variantsmentioning

confidence: 99%

Accurate Prediction of Protein Sequences for Proteogenomics Data Integration

Hagemeijer

Guryev

Horvatovich

2021

Methods in Molecular Biology

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This book chapter discusses proteogenomics data integration and provides an overview into the different omics layer involved in defining the proteome of a living organism. Various aspects of genome variability affecting either the sequence or abundance level of proteins are discussed in this book chapter, such as the effect of single-nucleotide variants or larger genomic structural variants on the proteome. Next, various sequencing technologies are introduced and discussed from a proteogenomics data integration perspective such as those providing short-and long-read sequencing and listing their respective advantages and shortcomings for accurate protein variant prediction using genomic/transcriptomics sequencing data. Finally, the various bioinformatics tools used to process and analyze DNA/RNA sequencing data are discussed with the ultimate goal of obtaining accurately predicted sample-specific protein sequences that can be used as a drop-in replacement in existing approaches for peptide and protein identification using popular database search engines such as MSFragger, SearchGUI/PeptideShaker.

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“…And the majority of AML events are correlative with abnormal chromosomal translocations, which generates the oncogenic fusion genes. Mounting studies have demonstrated the central roles of fusion genes in initiating the leukemogenesis (4)(5)(6). And the successful strategies are paralleled by the decrease or degradation of chimeric proteins (7,8).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…AML is frequently associated with chromatin rearrangement, including translocation and inversion, which generate oncogenic fusion proteins, among of which four most common chimeric proteins should be paid more attention, including AML1-ETO, PML-RARα, CBFβ-MYH11, and MLL-MLLT3 ( 4 , 6 , 32 – 34 ). Here we attempt to summarize the mutual interactions between HDACs and oncogenic fusion proteins involved in AML, providing a reference for the precise application of HDAC inhibitors and novel drug exploration against AML.…”

Section: Introductionmentioning

confidence: 99%

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Roles of Histone Deacetylases in Acute Myeloid Leukemia With Fusion Proteins

Zhang

Gao

2021

Front. Oncol.

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Accurate orchestration of gene expression is critical for the process of normal hematopoiesis, and dysregulation is closely associated with leukemogenesis. Epigenetic aberration is one of the major causes contributing to acute myeloid leukemia (AML), where chromosomal rearrangements are frequently found. Increasing evidences have shown the pivotal roles of histone deacetylases (HDACs) in chromatin remodeling, which are involved in stemness maintenance, cell fate determination, proliferation and differentiation, via mastering the transcriptional switch of key genes. In abnormal, these functions can be bloomed to elicit carcinogenesis. Presently, HDAC family members are appealing targets for drug exploration, many of which have been deployed to the AML treatment. As the majority of AML events are associated with chromosomal translocation resulting in oncogenic fusion proteins, it is valuable to comprehensively understand the mutual interactions between HDACs and oncogenic proteins. Therefore, we reviewed the process of leukemogenesis and roles of HDAC members acting in this progress, providing an insight for the target anchoring, investigation of hyperacetylated-agents, and how the current knowledge could be applied in AML treatment.

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Clinical and molecular consequences of fusion genes in myeloid malignancies

Cited by 13 publications

References 92 publications

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds

Accurate Prediction of Protein Sequences for Proteogenomics Data Integration

Roles of Histone Deacetylases in Acute Myeloid Leukemia With Fusion Proteins

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