MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences

L’Abbate, Alberto; Tolomeo, Doron; Cifola, Ingrid; Severgnini, Marco; Turchiano, Antonella; Augello, Bartolomeo; Squeo, Gabriella Maria; D’Addabbo, Pietro; Traversa, Debora; Daniele, Giulia; Lonoce, Angelo; Pafundi, Mariella; Carella, Massimo; Palumbo, Orazio; Dolnik, Anna; Muehlematter, Dominique; Schoumans, Jacqueline; Roy, Nadine Van; Bellis, Gianluca De; Martinelli, Giovanni; Merla, Giuseppe; Bullinger, Lars; Haferlach, Claudia; Storlazzi, Clelia Tiziana

doi:10.1038/s41375-018-0033-0

Cited by 76 publications

(58 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Their findings suggested that hsa_circ_0004277 could be a potential diagnostic biomarker in detecting early relapse. Another circRNA, circPVT1, was overexpressed in AML harboring oncogene MYC amplification [147], and this association could hint that circPVT1 might impact the survival of AML patients.…”

Section: Aberrant Circrna Expression Levels In Acute Myeloid Leukemiamentioning

confidence: 99%

“…Overexpression in AML-amp Unknown [147] Abbreviations: amp amplicons involving chromosome band 8q24, BM bone marrow, PB peripheral blood, CN-AML cytogenetically normal AML, THP-1/ADM cell doxorubicin (ADM)-resistant THP-1 AML cell al. identified that lncRNA MEG3 could be activated by WT1 and TET2 and it acted as a cofactor of WT1, enhancing leukemogenesis [172].…”

Section: Mir-496mentioning

confidence: 99%

See 1 more Smart Citation

Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia

et al. 2019

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a malignant tumor of the immature myeloid hematopoietic cells in the bone marrow (BM). It is a highly heterogeneous disease, with rising morbidity and mortality in older patients. Although researches over the past decades have improved our understanding of AML, its pathogenesis has not yet been fully elucidated. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are three noncoding RNA (ncRNA) molecules that regulate DNA transcription and translation. With the development of RNA-Seq technology, more and more ncRNAs that are closely related to AML leukemogenesis have been discovered. Numerous studies have found that these ncRNAs play an important role in leukemia cell proliferation, differentiation, and apoptosis. Some may potentially be used as prognostic biomarkers. In this systematic review, we briefly described the characteristics and molecular functions of three groups of ncRNAs, including lncRNAs, miRNAs, and circRNAs, and discussed their relationships with AML in detail.

show abstract

Section: Aberrant Circrna Expression Levels In Acute Myeloid Leukemiamentioning

confidence: 99%

Section: Mir-496mentioning

confidence: 99%

Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia

et al. 2019

View full text Add to dashboard Cite

show abstract

“…For example, SOX2OT (62), LINC00312 (63), TCL6 and PVT1, are are promoter methylated in one of the three subtypes. The lncRNA, PVT1 was reported for its MYC activity(64,65) and as oncogenic lncRNA with multiple roles in cell growth, dysfunction, and differentiation in AML(66). Both lncRNAs, LINC00312 and TCL6 have been extensively investigated on expression levels but not on the epigenetic level.…”

mentioning

confidence: 99%

Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia

James

Schroêder

Neumann

et al. 2018

Preprint

View full text Add to dashboard Cite

Recent studies implicated that long noncoding RNAs (lncRNAs) may play a role in the progression and development of acute lymphoblastic leukemia, however, this role is not yet clear. In order to unravel the role of lncRNAs associated with Bcell precursor Acute Lymphoblastic Leukemia (BCPALL) subtypes, we performed transcriptome sequencing and DNA methylation array across 82 BCPALL samples from three molecular subtypes (DUX4, Phlike, and Near Haploid or High Hyperdiploidy). Unsupervised clustering of BCPALL samples on the basis of their lncRNAs on transcriptome and DNA methylation profiles revealed robust clusters separating three molecular subtypes. Using extensive computational analysis, we developed a comprehensive catalog of 1235 aberrantly dysregulated BCPALL subtypespecific lncRNAs with altered expression and methylation patterns from three subtypes of BCPALL. By analyzing the coexpression of subtypespecific lncRNAs and proteincoding genes, we inferred key molecular processes in BCPALL subtypes. A strong correlation was identified between the DUX4 specific lncRNAs and activation of TGF and Hippo signaling pathways. Similarly, Phlike specific lncRNAs were β correlated with genes involved in activation of PI3KAKT, mTOR, and JAKSTAT signaling pathways. Interestingly, the relapsespecific differentially expressed lncRNAs correlated with the activation of metabolic and signaling pathways. Finally, we showed a set of epigenetically altered lncRNAs facilitating the expression of tumor genes located at their cis location. Overall, our study provides a comprehensive set of novel subtype and relapse specific lncRNAs in BCPALL. Our findings suggest a wide range of molecular pathways are associated with lncRNAs in BCPALL subtypes and provide a foundation for functional investigations that could lead to new therapeutic approaches. The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/365429 doi: bioRxiv preprint first posted online Jul. 9, 2018; Author SummaryAcute lymphoblastic leukemia is a heterogeneous blood cancer, with multiple molecular subtypes, and with high relapse rate. We are far from the complete understanding of the rationale behind these subtypes and high relapse rate. Long noncoding (lncRNAs) has emerged as a novel class of RNA due to its diverse mechanism in cancer development and progression. LncRNAs does not code for proteins and represent around 70% of human transcripts. Recently, there are a number of studies used lncRNAs expression profile in the classification of various cancers subtypes and displayed their correlation with genomic, epigenetic, pathological and clinical features in diverse cancers. Therefore, lncRNAs can account for heterogeneity and has independent prognostic value in various cancer subtypes.However, lncRNAs defining the molecular subtypes of BCPALL are not portrayed yet. Here, we describe a set of relapse and subtypespecific lncRNAs from three major BCPALL subtypes and define their potential functions and epigenetic regulation. Our data uncover ...

show abstract

“…In AML, glioblastoma and prostate cancer, overexpression of c-Myc or LSD1 has already been reported. 32, [38][39][40][41] However, there is no report on whether both are overexpressed together. Therefore, we examined the relationship between LSD1 expression and c-Myc expression in various human tumors [31][32][33][34] in The Cancer Genome Atlas (TCG A) database using cBioPortal.…”

Section: Resultsmentioning

confidence: 99%

Lysine-Specific Demethylase 1 (LSD1/KDM1A) Is a Novel Target Gene of c-Myc

Nagasaka

Tsuzuki

Ozeki

et al. 2019

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Lysine-specific demethylase 1 (LSD1/KDM1A) is a histone demethylase and specifically catalyzes the demethylation of mono-and di-methylated histone H3 lysine 4 (H3K4). The LSD1-mediated demethylation of H3K4 promotes the assembly of the c-Myc-induced transcription initiation complex. Although LSD1 and c-Myc are both strongly expressed in human cancers, the mechanisms by which their activities are coordinated remain unclear. We herein demonstrated that LSD1 is a direct target gene of c-Myc. The knockdown of c-Myc decreased the expression of LSD1 in several cancer cell lines. We identified two non-canonical Eboxes in the proximal promoter region of the LSD1 gene. A chromatin immunoprecipitation assay showed that c-Myc bound to these E-boxes in the LSD1 promoter. Importantly, LSD1 mRNA expression correlated with c-Myc expression in human acute myeloid leukemia (AML), glioblastoma, stomach adenocarcinoma, and prostate adenocarcinoma. The present results suggest that LSD1 is induced by c-Myc and forms a positive feedback mechanism in transcription reactions by c-Myc.

show abstract

MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences

Cited by 76 publications

References 58 publications

Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia

Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia

Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia

Lysine-Specific Demethylase 1 (LSD1/KDM1A) Is a Novel Target Gene of c-Myc

Contact Info

Product

Resources

About