Characteristics of Cohesin Mutation in Acute Myeloid Leukemia and Its Clinical Significance

Han, Caixia; Gao, Xuefeng; Li, Yonghui; Zhang, Juan; Yang, Erna; Zhang, Li; Yu, Li

doi:10.3389/fonc.2021.579881

Cited by 14 publications

(8 citation statements)

References 88 publications

(146 reference statements)

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“…Developmental syndromes, cancers, and cellular phenotypes that are caused by cohesin deficiency have been the subject of several comprehensive and very recent reviews [26,[52][53][54][55][56][57][58]; therefore, these topics will not be revisited here. The concepts that genes are regulated by cohesin, and that this function of cohesin contributes to human developmental disease and cancer, have emerged from several studies over the years (Fig.…”

Section: Introductionmentioning

confidence: 99%

Full circle: a brief history of cohesin and the regulation of gene expression

Horsfield

2022

The FEBS Journal

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The cohesin complex has a range of crucial functions in the cell. Cohesin is essential for mediating chromatid cohesion during mitosis, for repair of double‐strand DNA breaks, and for control of gene transcription. This last function has been the subject of intense research ever since the discovery of cohesin's role in the long‐range regulation of the cut gene in Drosophila. Subsequent research showed that the expression of some genes is exquisitely sensitive to cohesin depletion, while others remain relatively unperturbed. Sensitivity to cohesin depletion is also remarkably cell type‐ and/or condition‐specific. The relatively recent discovery that cohesin is integral to forming chromatin loops via loop extrusion should explain much of cohesin's gene regulatory properties, but surprisingly, loop extrusion has failed to identify a ‘one size fits all’ mechanism for how cohesin controls gene expression. This review will illustrate how early examples of cohesin‐dependent gene expression integrate with later work on cohesin's role in genome organization to explain mechanisms by which cohesin regulates gene expression.

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Section: Introductionmentioning

confidence: 99%

Full circle: a brief history of cohesin and the regulation of gene expression

Horsfield

2022

The FEBS Journal

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“…When TET2 -mutated AML patients where partitioned into TET2 vs IDH1/2-to-TET2 subgroups, the latter had a significantly better survival, corroborating our findings (Figure 3, Supplementary Table 2). The prognostic significance of RAD21 mutations in AML is controversial as some studies described them as independent factors for a longer OS, while others found no differences in survival [29]. According to ASCETIC, mutated RAD21 is associated with better outcome, shedding new light on the prognostic value of RAD21 mutations in AML.…”

Section: Myeloid Malignanciesmentioning

confidence: 99%

Evolutionary signatures of human cancers revealed via genomic analysis of over 35,000 patients

Fontana

Crespiatico

Crippa

et al. 2023

Preprint

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By leveraging the ever-increasing availability of cancer omics data and the continuous advances in cancer data science and machine learning, we have discovered the existence of cancer type-specific evolutionary signatures associated with different disease outcomes. These signatures represent "favored trajectories" of acquisition of driver mutations that are repeatedly detected in patients with similar prognosis. In this work, we present a novel framework named ASCETIC (Agony-baSed Cancer EvoluTion InferenCe) that extracts such signatures from NGS experiments generated by different technologies such as bulk and single-cell sequencing data. In our study, we applied ASCETIC to (i) single-cell sequencing data from 146 patients with distinct myeloid malignancies and bulk whole-exome sequencing data from 366 acute myeloid leukemia patients, (ii) multi-region sequencing data from 100 early-stage lung cancer patients from the TRACERx project, (iii) whole-exome/genome sequencing data from more than 10,000 Pan-Cancer Atlas samples, and (iv) targeted bulk sequencing data from more than 25,000 MSK-MET metastatic patients (both datasets including multiple cancer types). As a result, we extracted different cancer (sub)type-specific single-nucleotide variants evolutionary signatures associated with clusters of patients with statistically significant different prognoses. In addition, we conducted several validations using diverse and previously unexplored datasets to evaluate the reliability and applicability of the evolutionary signatures extracted by ASCETIC. Such analyses provided evidence of the robustness and generalizability of the identified evolutionary patterns.

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“…Therefore, cohesin mutations may lead to aneuploidy. Additionally, the cohesin complex is involved in modulating gene expression through genome organization by increasing DNA accessibility for transcription factors [ 275 , 276 ]. However, mutations in the cohesin complex do not cause aneuploidy in AML, suggesting that the control of the gene expression function by the cohesin complex is crucial for leukemogenesis [ 277 ].…”

Section: Mouse Models Of Cohesin Complex Genes In Myeloid Malignanciesmentioning

confidence: 99%

Mouse Models of Frequently Mutated Genes in Acute Myeloid Leukemia

Mohanty

Heuser

2021

Cancers

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Acute myeloid leukemia is a clinically and biologically heterogeneous blood cancer with variable prognosis and response to conventional therapies. Comprehensive sequencing enabled the discovery of recurrent mutations and chromosomal aberrations in AML. Mouse models are essential to study the biological function of these genes and to identify relevant drug targets. This comprehensive review describes the evidence currently available from mouse models for the leukemogenic function of mutations in seven functional gene groups: cell signaling genes, epigenetic modifier genes, nucleophosmin 1 (NPM1), transcription factors, tumor suppressors, spliceosome genes, and cohesin complex genes. Additionally, we provide a synergy map of frequently cooperating mutations in AML development and correlate prognosis of these mutations with leukemogenicity in mouse models to better understand the co-dependence of mutations in AML.

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Characteristics of Cohesin Mutation in Acute Myeloid Leukemia and Its Clinical Significance

Cited by 14 publications

References 88 publications

Full circle: a brief history of cohesin and the regulation of gene expression

Full circle: a brief history of cohesin and the regulation of gene expression

Evolutionary signatures of human cancers revealed via genomic analysis of over 35,000 patients

Mouse Models of Frequently Mutated Genes in Acute Myeloid Leukemia

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