EVI1 protein interaction dynamics: Targetable for therapeutic intervention?

Paredes, Roberto; Doleschall, Nora; Connors, Kathleen; Geary, Bethany; Meyer, Stefan

doi:10.1016/j.exphem.2021.12.398

Cited by 3 publications

(2 citation statements)

References 82 publications

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“…65 The MECOM (MDSÀEVI1(Ecotropic Viral Integration Site 1 gene) complex) locus, located at chromosomal band 3q26, encodes several proteins, including EVI1. MECOM rearrangements lead to overexpression of EVI1, a nuclear transcription factor involved in AML development, 66,67 that is characteristically associated with a very poor prognosis. Other rare recurrent chromosomal translocations in AML are shown in Table S2.…”

Section: Aml With Recurrent Genetic Abnormalitiesmentioning

confidence: 99%

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

Falini

Martelli

2023

American J Hematol

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Several editions of the World Health Organization (WHO) classifications of lympho‐hemopoietic neoplasms in 2001, 2008, and 2016 served as the international standard for diagnosis. Since the 4th WHO edition, here referred as WHO‐HAEM4, significant clinico‐pathological, immunophenotypic, and molecular advances have been made in the field of myeloid neoplasms, which have contributed to refine diagnostic criteria, to upgrade entities previously defined as provisional and to identify new entities. This process has resulted in two recent classification proposals of myeloid neoplasms: the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO‐HAEM5). In this paper, we review and compare the two classifications in terms of diagnostic criteria and entity definition, with a focus on adult myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML). The goal is to provide a tool to facilitate the work of pathologists, hematologists and researchers involved in the diagnosis and treatment of these hematological malignancies.

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Section: Aml With Recurrent Genetic Abnormalitiesmentioning

confidence: 99%

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

Falini

Martelli

2023

American J Hematol

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“…The function of EVI1 is critically modulated by posttranslational modifications including phosphorylation, sumoylation, ubiquitylation, and monomethylation ( 195 ). Constitutive expression of EVI1 through bone marrow transplantation in mice recapitulates phenotypes resembling MDS.…”

Section: Biological Mechanisms Of Bmf And/or Hm Predisposition Tfsmentioning

confidence: 99%

Transcription factor genetics and biology in predisposition to bone marrow failure and hematological malignancy

Zerella,

Homan,

Arts

et al. 2023

Front. Oncol.

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Transcription factors (TFs) play a critical role as key mediators of a multitude of developmental pathways, with highly regulated and tightly organized networks crucial for determining both the timing and pattern of tissue development. TFs can act as master regulators of both primitive and definitive hematopoiesis, tightly controlling the behavior of hematopoietic stem and progenitor cells (HSPCs). These networks control the functional regulation of HSPCs including self-renewal, proliferation, and differentiation dynamics, which are essential to normal hematopoiesis. Defining the key players and dynamics of these hematopoietic transcriptional networks is essential to understanding both normal hematopoiesis and how genetic aberrations in TFs and their networks can predispose to hematopoietic disease including bone marrow failure (BMF) and hematological malignancy (HM). Despite their multifaceted and complex involvement in hematological development, advances in genetic screening along with elegant multi-omics and model system studies are shedding light on how hematopoietic TFs interact and network to achieve normal cell fates and their role in disease etiology. This review focuses on TFs which predispose to BMF and HM, identifies potential novel candidate predisposing TF genes, and examines putative biological mechanisms leading to these phenotypes. A better understanding of the genetics and molecular biology of hematopoietic TFs, as well as identifying novel genes and genetic variants predisposing to BMF and HM, will accelerate the development of preventative strategies, improve clinical management and counseling, and help define targeted treatments for these diseases.

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Clinical Significance of Dynamic Monitoring of EVI1 Gene Expression in Pediatric Acute Myeloid Leukemia

Zhang,

Li,

Wang

et al. 2024

Preprint

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Objective To investigate the clinical significance of dynamic monitoring ecotropic virus integration site-1 (EVI1) expression in childhood acute myeloid leukemia (AML). Methods A retrospective analysis was conducted on 113 pediatric AML patients of Wuhan Children's Hospital from 2014 to 2022. The correlation between EVI1 expression levels and clinical indicators including clinical characteristics, first complete remission (CR1), relapse, and overall survival (OS) was analyzed. Receiver operating characteristic (ROC) curve analysis was carried out to comprehend the influence of EVI1 expression on relapse. Results A total of 78 AML children with EVI1 expression at initial diagnosis were eligible, divided into EVI1-positive (EVI1high) and EVI1-negative (EVI1low) groups. FAB classification (P = 0.047) and abnormal karyotype (P = 0.009) showed significant differences between the two groups. The proportion of EVI1 high in individuals with complex and/or monomeric karyotypes was significantly higher than in other cases (P = 0.032). When completing the first induction therapy, the EVI1high group showed a significantly lower CR1 rate than the EVI1low group (P = 0.015). Among 51 cases with EVI1 expression dynamically monitored, those with EVI1 overexpression more than twice had significantly shorter OS (P < 0.05). Among 19 non-HSCT patients undergoing three EVI1 assessments during induction therapy, those with EVI1 overexpression over once had higher relapse rates (P = 0.045). In addition, EVI1 expression level ≥ 83.38% significantly predicted relapse (AUC = 0.833). Conclusion Aberrantly high expression of EVI1 in pediatric AML was associated with poor prognosis. Continuous and dynamic monitoring of EVI1 expression promotes prognostic evaluation. We add some insights into the impact of EVI1 on the AML patients’ OS and survival.

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EVI1 protein interaction dynamics: Targetable for therapeutic intervention?

Cited by 3 publications

References 82 publications

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

Transcription factor genetics and biology in predisposition to bone marrow failure and hematological malignancy

Clinical Significance of Dynamic Monitoring of EVI1 Gene Expression in Pediatric Acute Myeloid Leukemia

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