The Stat3/5 Signaling Biosignature in Hematopoietic Stem/Progenitor Cells Predicts Response and Outcome in Myelodysplastic Syndrome Patients Treated with Azacitidine

Miltiades, Paraskevi; Lamprianidou, Eleftheria; Vassilakopoulos, Theodoros P.; Papageorgiou, Sotirios G.; Galanopoulos, Athanasios; Kontos, Christos K.; Adamopoulos, Panagiotis G.; Nakou, Evangelia; Vakalopoulou, Sofia; Garypidou, Vassilia; Papaioannou, Maria; Hatjiharissi, Evdoxia; Papadaki, Helen Α.; Spanoudakis, Emmanouil; Pappa, Vasiliki; Scorilas, Andreas; Tsatalas, Costas; Kotsianidis, Ιoannis

doi:10.1158/1078-0432.ccr-15-1288

Cited by 16 publications

(6 citation statements)

References 49 publications

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“…To date, a lot of genes are known to express alternative splice variants, some of which may have significant clinical value (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). The family of KLKs constitutes such a prominent example (28,29), as particular splice variants of the KLK1-KLK15 genes have been highlighted as putative biomarkers in human malignancies (30)(31)(32)(33)(34)(35).…”

Section: Biological and Clinical Significance Of Splice Variantsmentioning

confidence: 99%

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

Adamopoulos¹,

Theodoropoulou²,

Scorilas³

2018

Ann. Transl. Med.

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Next-generation sequencing (NGS) can provide researchers with high impact information regarding alternative splice variants or transcript identifications. However, the enormous amount of data acquired from NGS platforms make the analysis of alternative splicing events hard to accomplish. For this reason, we designed the "Alternative Splicing Detection Tool" (ASDT), an algorithm that is capable of identifying alternative splicing events, including novel ones from high-throughput NGS data. ASDT is available as a PERL script at http://aias.biol.uoa.gr/~mtheo and can be executed on any system with PERL installed. In addition to the detection of annotated and novel alternative splicing events from high-throughput NGS data, ASDT can also analyze the intronic regions of genes, thus enabling the detection of novel cryptic exons residing in annotated introns, extensions of previously annotated exons, or even intron retentions. Consequently, ASDT demonstrates many innovative and unique features that can efficiently contribute to alternative splicing analysis of NGS data.

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Section: Biological and Clinical Significance Of Splice Variantsmentioning

confidence: 99%

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

Adamopoulos¹,

Theodoropoulou²,

Scorilas³

2018

Ann. Transl. Med.

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“…The mechanisms of resistance to HMAs in the setting of MDS have been actively explored. Diverse molecular mechanisms contributing to HMA resistance have been proposed, including integrin α5-mediated hematopoietic progenitor cell quiescence [ 111 ], elevated CDA/DCK ratio [ 112 ], increased RNA:m5C and NSUN1-/BRD4-associated active chromatin [ 113 ], elevated BCL2L10 expression ( 114 ), disturbed STAT3/5 signaling [ 115 ] and high number of mutations in the DNA methylation pathway, notably in TET2 gene [ 116 – 119 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia

Yang

Zhang

et al. 2022

Exp Hematol Oncol

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Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell diseases arising from the bone marrow (BM), and approximately 30% of MDS eventually progress to AML, associated with increasingly aggressive neoplastic hematopoietic clones and poor survival. Dysregulated immune microenvironment has been recognized as a key pathogenic driver of MDS and AML, causing high rate of intramedullary apoptosis in lower-risk MDS to immunosuppression in higher-risk MDS and AML. Immune checkpoint molecules, including programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), play important roles in oncogenesis by maintaining an immunosuppressive tumor microenvironment. Recently, both molecules have been examined in MDS and AML. Abnormal inflammatory signaling, genetic and/or epigenetic alterations, interactions between cells, and treatment of patients all have been involved in dysregulating PD-1/PD-L1 signaling in these two diseases. Furthermore, with the PD-1/PD-L1 pathway activated in immune microenvironment, the milieu of BM shift to immunosuppressive, contributing to a clonal evolution of blasts. Nevertheless, numerous preclinical studies have suggested a potential response of patients to PD-1/PD-L1 blocker. Current clinical trials employing these drugs in MDS and AML have reported mixed clinical responses. In this paper, we focus on the recent preclinical advances of the PD-1/PD-L1 signaling in MDS and AML, and available and ongoing outcomes of PD-1/PD-L1 inhibitor in patients. We also discuss the novel PD-1/PD-L1 blocker-based immunotherapeutic strategies and challenges, including identifying reliable biomarkers, determining settings, and exploring optimal combination therapies.

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“…), permitting their easy quantification paving the way for the development of non-invasive assays in the era of personalized medicine (84,85). Moreover, proteins that are targeted by important miRNAs could also participate in such multiparametric panels of biomarkers (86)(87)(88)(89), along with clinical markers (90)(91)(92). tRFs tRFs constitute novel sncRNA molecules generated by specific cleavage of tRNA transcripts.…”

Section: Introductionmentioning

confidence: 99%

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

Diamantopoulos¹,

Tsiakanikas²,

Scorilas³

2018

Ann. Transl. Med.

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100

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Non-coding RNAs (ncRNAs) constitute a heterogeneous group of RNA molecules in terms of biogenesis, biological function as well as length and structure. These biological molecules have gained attention recently as a potentially crucial layer of tumor cell progression or regulation. ncRNAs are expressed in a broad spectrum of tumors, and they play an important role not only in maintaining but also in promoting cancer development and progression. Recent discoveries have revealed that ncRNAs may act as key signal transduction mediators in tumor signaling pathways by interacting with RNA or proteins. These results reinforce the hypothesis, that ncRNAs constitute therapeutic targets, and point out their clinical potential as stratification markers. The major purpose of this review is to mention the emergence of the importance of ncRNAs, as molecules which are correlated with cancer, and to discuss their clinical implicit as prognostic diagnostic indicators, biomarkers, and therapeutic targets.

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The Stat3/5 Signaling Biosignature in Hematopoietic Stem/Progenitor Cells Predicts Response and Outcome in Myelodysplastic Syndrome Patients Treated with Azacitidine

Cited by 16 publications

References 49 publications

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

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