Treatment with 5-Azacytidine improves clinical outcome in high-risk MDS patients in the ‘real life’ setting: A single center observational study

Papageorgiou, Sotirios G.; Vasilatou, Diamantina; Kontos, Christos K.; Foukas, Periklis; Kefala, Maria; Ioannidou, E.; Bazani, Efthymia; Dimitriadis, George; Pappa, Vasiliki

doi:10.1179/1607845415y.0000000039

Cited by 14 publications

(14 citation statements)

References 18 publications

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“…Moreover, the expression of a splice variant could be combined with clinical markers; for instance, the expression of BCL2L12 splice variant 1 and BCL2 variant alpha in malignant B cells of patients with chronic lymphocytic leukemia could be combined with lymphocyte count and/or other clinical features to provide a better prognostic system than the currently used ones (48,52). Similarly, expression of important transcripts resulting from alternative splicing in blasts of patients with myelodysplastic syndromes could be used along with novel markers such as monosomal karyotype to predict prognosis (53), treatment decision-making (54), or patients' response to therapy (55,56), at is has recently been proposed. Distinct 3'-untranslated regions (3'-UTRs) of splice variants of a single protein-coding gene resulting from alternative splicing may have other implications, including different regulatory properties.…”

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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“…), 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.

105

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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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“…Patients with intermediate‐2 and high‐risk MDS have poor prognosis and increased risk of transformation to AML. 5‐AZA is 1 of the first‐line treatment options for this group of patients, and both clinical trials and real‐world data have demonstrated improved clinical outcome for patients responding to 5‐AZA . However, there is a group of patients who have SD as BR.…”

Section: Discussionmentioning

confidence: 99%

“…cal trials (AZA 001) and in the real-life setting. 5,6 According to the AZA 001 study, this impact on survival was observed in 5-AZA-treated patients despite the relatively low response rates of 29% (complete remission (CR) 17% and partial remission (PR) 12%). 7 The median number of cycles required to achieve initial response (IR) was 3, while 81% of patients needed up to 6 cycles and 90% of patients needed up to 9 cycles to reach their IR.…”

mentioning

confidence: 99%

The outcome of patients with high‐risk MDS achieving stable disease after treatment with 5‐azacytidine: A retrospective analysis of the Hellenic (Greek) MDS Study Group

Papageorgiou

Kontos

Kotsianidis

et al. 2018

Hematological Oncology

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The demethylating factor 5-azacytidine (5-AZA) improves survival in intermediate-2 and high-risk myelodysplastic syndrome (MDS) patients [according to the International Prognostic Score System (IPSS)] responding to treatment. However, the outcome of patients achieving stable disease (SD) is unclear. This retrospective study of the Hellenic MDS Study Group included 353 intermediate-2 or high IPSS risk patients treated with 5-AZA. Forty-four out of 86 (51.6%) patients achieving SD and continuing treatment with 5-AZA showed a lower risk of transformation of MDS to acute myeloid leukemia (AML) and increased overall survival (OS), compared to SD patients who discontinued the treatment (estimated median AML-free survival = 38 months, 95% CI = 10.7-65.3 vs 15 months, 95% CI = 10.4-19.6, P < .001; estimated median OS = 20 months, 95% CI = 5.5-34.5 vs 11 months, 95% CI = 5.8-16.2, P < .001). Moreover, SD patients continuing treatment with 5-AZA had no differences in AML-free survival compared to patients showing response to 5-AZA (estimated median AML-free survival = 38 months, 95% CI = 10.7-65.3 vs 31 months, 95% CI = 23.6-38.4, P = .45; estimated median OS 20 months, 95% CI = 5.5-34.5 vs 25 months, 95% CI = 21.3-28.7, P = .50). In conclusion, MDS patients achieving SD in the first 6 months of treatment with 5-AZA as best response should continue receiving 5-AZA as they may benefit from prolonged treatment.

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Treatment with 5-Azacytidine improves clinical outcome in high-risk MDS patients in the ‘real life’ setting: A single center observational study

Abstract: In conclusion, 5-AZA is an effective treatment for high-risk MDS. Improved OS and EFS were found mainly in patients who responded to the treatment while ΔWPSS seems to represent a promising future prognostic tool.

Cited by 14 publications

References 18 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

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

The outcome of patients with high‐risk MDS achieving stable disease after treatment with 5‐azacytidine: A retrospective analysis of the Hellenic (Greek) MDS Study Group

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