Retrospective analysis of 36 fusion genes in 2479 Chinese patients of de novo acute lymphoblastic leukemia

Chen, Xue; Wang, Fang; Zhang, Yang; Wang, Mangju; Tian, Wenjun; Teng, Wen; Ma, Xiaoli; Guo, Lei; Fang, Jiancheng; Zhang, Ying; Zhu, Ping; Liu, Hongxing

doi:10.1016/j.leukres.2018.08.009

Cited by 22 publications

(21 citation statements)

References 24 publications

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“…Other genes with hypomethylation and corresponding higher expression in t(8;21) vs. other subtypes included: MGMT (methylguanine-DNA methyltransferase), a tumor suppressor gene that has been associated with risk of AML development [ 38 ]; MPL (myeloproliferative leukemia virus oncogene), which has been shown to be essential for survival and self-renewal of human preleukemic t(8;21) cells [ 39 ]. Wildtype MPL has been shown to be overexpressed in t(8;21) AML and promote leukemia development via PI3K/AKT axis activation [ 40 ]; KDM4B , a histone specific demethylase, has been implicated in regulating expression of genes required for maintenance of hematopoiesis [ 41 ]; TCF3 , a fusion partner of PBX1 and 4-HLF in ALL [ 42 , 43 , 44 , 45 ], however its importance in AML is not currently known; and ABR that codes for an Active BCR related is involved in deactivation of RAC1 (ras-related C3 botulinum toxin substrate 1) important for hematopoiesis and leukemia [ 46 ]; we observed hypomethylation and low expression of ABR in t(8;21) ( Figure 2 B). Recently, ABR has been shown to be an enhancer of C/EBPa , a key mediator of myeloid differentiation, associated with azacytidine-induced apoptosis and as a favorable prognostic factor in AML [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

Lamba

Cao

Raimondi

et al. 2020

Cancers

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Acute Myeloid Leukemia (AML) is characterized by recurrent genetic and cytogenetic lesions that are utilized for risk stratification and for making treatment decisions. In recent years, methylation dysregulation has been extensively studied and associated with risk groups and prognosis in adult AML, however, such studies in pediatric AML are limited. Moreover, the mutations in epigenetic genes such as DNMT3A, IDH1 or IDH2 are almost absent or rare in pediatric patients as compared to their abundance in adult AML. In the current study, we evaluated methylation patterns that occur with or independent of the well-defined cytogenetic features in pediatric AML patients enrolled on multi-site AML02 clinical trial (NCT00136084). Our results demonstrate that unlike adult AML, cytosine DNA methylation does not result in significant unique clusters in pediatric AML, however, DNA methylation signatures correlated significantly with the most common and recurrent cytogenetic features. Paired evaluation of DNA methylation and expression identified genes and pathways of biological relevance that hold promise for novel therapeutic strategies. Our results further demonstrate that epigenetic signatures occur complimentary to the well-established chromosomal/mutational landscape, implying that dysregulation of oncogenes or tumor suppressors might be leveraging both genetic and epigenetic mechanisms to impact biological pathways critical for leukemogenesis.

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Section: Resultsmentioning

confidence: 99%

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

Lamba

Cao

Raimondi

et al. 2020

Cancers

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“… 6 , 9 , 16 - 21 Another two studies also mentioned patients with the SET-CAN fusion gene but were not included because they lacked the detailed information. 22 , 23 Most of the reported T-ALL cases with the SET-CAN fusion gene occurred in young and middle-aged men. Flow cytometry analysis showed that patients not only had the differentiation antigen of T lymphocytes, but also expressed many myeloid antigens, suggesting that the tumor cells of these patients may be in the early stage of T lymphocyte development.…”

Section: Discussionmentioning

confidence: 99%

<p><em>SET-CAN</em> Fusion Gene in Acute Leukemia and Myeloid Neoplasms: Report of Three Cases and a Literature Review</p>

Zhang¹,

Zhang²,

Li³

et al. 2020

OTT

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Objective: To investigate the characteristics of hematological malignancies in patients with the SET-CAN fusion gene and provide a literature review. Methods: We retrospectively analyzed the clinical data of three cases of acute leukemia and myeloid neoplasms harboring the SET-CAN fusion gene who were treated at our hospital. Their clinical manifestations, pathological results and treatment strategies were investigated. Results: The three cases were diagnosed with T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia (AML) and myeloid sarcoma (MS), respectively. Karyotype analyses identified a normal result in all three patients. Subsequently, we confirmed del(9q34) utilizing FISH analysis. Mutation of the BRAF gene was detected in case 1, while mutations in PHF6 and BCOR were detected in case 2, which have not been officially reported in patients with SET-CAN fusions. Finally, relevant literature focusing on adult patients with hematological malignancies harboring the SET-CAN fusion gene were summarized. Conclusion: Adult patients with the SET-CAN fusion gene were rare among cases of hematological malignancies. There was a large degree of heterogeneity between different patients. Notably, some patients remained sensitive to chemotherapy. Overall prognosis may be related to the type of disease and other cytogenetic abnormalities. Systemic cytogenetic and molecular studies are needed to make accurate diagnoses. Additional cases need to be accumulated and summarized to better understand these diseases.

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“…In this study, 36 commonly reported FGs in hematological malignancies in a large cohort of Chinese acute leukemia patients were retrospectively analyzed. 6,7 It was found that 23 FGs were detected in 1292 (41.21%) of 3135 acute myeloid leukemia (AML) cases, and 17 FGs were detected in 712 (28.72%) of 2479 acute lymphoblastic leukemia (ALL) cases. The co-occurrence of two FGs was observed in only 0.22% of AML and 0.24% of ALL patients.…”

Section: Traditional Methods and Limitations Of Fgs Identificationmentioning

confidence: 99%

“…Today, screening multiple FGs simultaneously and then quantitatively monitoring the positive ones has become a routine clinical application. [6][7][8]…”

Section: Introductionmentioning

confidence: 99%

Advances in Fusion Gene Research and Fusion Gene Families in Hematological Malignancies

Chen

Wang

et al. 2019

Int J Med Rev

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Fusion genes (FGs) are major molecular biological abnormalities in hematological malignancies and have become well-established molecular markers for disease classification, risk stratification, and targeted therapies. The long tail phenomenon is observed in the distribution of FGs, which means that except for dozens of the most common FGs, the positive rates of the other FGs are all below 1%, even if they have been frequently reported in the literature. However, the total positive rate of these singly relatively rare FGs is actually not low due to their wide variety and numerous members. We therefore put forward the conception "fusion gene family, FG-FM" to describe fusions that share one common protagonist gene with different partner genes. Most of the FGs in hematological malignancies discovered to date can be classified into about 20 major families. Based on the characteristics of the currently reported FGs, it can be expected that although a great many FGs may be identified in the future, the total number of FG-FMs is rather limited. FGs in the same FG-FM often have similarities in pathogenicity, clinical features, and treatment outcomes. Classifying FGs according to FG-FMs will aid in understanding their pathogenicity and optimizing detection schemes.

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Retrospective analysis of 36 fusion genes in 2479 Chinese patients of de novo acute lymphoblastic leukemia

Cited by 22 publications

References 24 publications

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

<p><em>SET-CAN</em> Fusion Gene in Acute Leukemia and Myeloid Neoplasms: Report of Three Cases and a Literature Review</p>

Advances in Fusion Gene Research and Fusion Gene Families in Hematological Malignancies

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