New therapeutic approaches in myelodysplastic syndromes: Hypomethylating agents and lenalidomide

Loiseau, Clémence; Ali, Ashfaq; Itzykson, Raphaël

doi:10.1016/j.exphem.2015.05.014

Cited by 7 publications

(4 citation statements)

References 157 publications

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“…Among the lncRNAs with significantly altered levels between RESPs and nRESPs (details included in Table V), four lincRNAs were found from the 21p11.2 chromosomal locus (CH507-513H4. [3][4][5][6] and several other lncRNAs from different categories (lincRNAs, antisense RNAs, rRNAs, miRNA precursors, etc. ), the majority of which are completely unannotated (their details are included in Table VI).…”

Section: Resultsmentioning

confidence: 99%

Noncoding RNAs and Their Response Predictive Value in Azacitidine-treated Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-related Changes

Merkerová

Kléma

Kundrat

et al. 2022

Cancer Genomics Proteomics

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Background/Aim: Prediction of response to azacitidine (AZA) treatment is an important challenge in hematooncology. In addition to protein coding genes (PCGs), AZA efficiency is influenced by various noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular RNAs (circRNAs), and transposable elements (TEs). Materials and Methods: RNA sequencing was performed in patients with myelodysplastic syndromes or acute myeloid leukemia before AZA treatment to assess contribution of ncRNAs to AZA mechanisms and propose novel disease prediction biomarkers. Results: Our analyses showed that lncRNAs had the strongest predictive potential. The combined set of the best predictors included 14 lncRNAs, and only four PCGs, one circRNA, and no TEs. Epigenetic regulation and recombinational repair were suggested as crucial for AZA response, and network modeling defined three deregulated lncRNAs ) associated with these processes. Conclusion: The expression of various ncRNAs can influence the effect of AZA and new ncRNA-based predictive biomarkers can be defined.Myelodysplastic syndromes (MDS) are a heterogenous group of clonal malignancies characterized by ineffective hematopoiesis resulting in peripheral cytopenia and hypercellular bone marrow dysplasia. MDS patients have an increased tendency to transform to acute myeloid leukemia (AML). When the disease progresses to leukemia, prognosis is clearly unfavorable, with an estimated survival of less than one year (1). The prognosis of MDS patients is assessed based on the Revised International Prognostic Scoring System (IPSS-R) and depends on the number and severity of cytopenia, percentage of bone marrow (BM) blasts and cytogenetics (2).Azacitidine (AZA) is a hypomethylating agent (HMA) that is currently used as a standard care for patients with higher-risk MDS or AML with 20-30% BM blasts when not eligible for intensive chemotherapy and allogeneic transplantation. AZA is a cytidine analogue that, at low doses, inhibits DNA methyltransferases, resulting in DNA hypomethylation. At high doses, AZA is directly cytotoxic to abnormal BM hematopoietic cells because of its incorporation into DNA and RNA (3). Although AZA is extensively used, 30-40% of patients fail to respond or relapse after treatment (4). The International Working Group (IWG) proposed standardized response criteria for evaluating clinically significant responses in MDS (5). Stratification of patients who will benefit from those who will not respond to AZA is essential. In addition to the high costs associated with the treatment, an important issue lies in prolonged exposure to AZA as current recommendations are for a minimum of 6 months of treatment before deeming it a failure. Therefore, proper prediction biomarkers that could potentially prevent prolonged unnecessary adverse effects in AZA-nonresponsive patients are needed. 205This article is freely accessible online.

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Section: Resultsmentioning

confidence: 99%

Noncoding RNAs and Their Response Predictive Value in Azacitidine-treated Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-related Changes

Merkerová

Kléma

Kundrat

et al. 2022

Cancer Genomics Proteomics

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“…Two hypomethylating agents (azacitidine and decitabine) inhibit DNA methyltransferases 3A and 3B and reverse the aberrant methylation involved in MDS progression to AML. The development of novel therapeutic strategies in MDS is dependent on recent advances in the molecular pathogenesis of MDS [6,16,[28][29][30][31][32][33][34][35][36][37][38][39]. Various combination therapies in MDS are also intensively studied [27,40,41].…”

Section: Ota Fuchsmentioning

confidence: 99%

Introductory Chapter: Myelodysplastic Syndromes

Fuchs¹

2016

Myelodysplastic Syndromes

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“…Most patients treated with a hypomethylating agent do not achieve an objective response. Combinatorial treatment with AZA and Revlimid demonstrated synergistic effects in MDS owing to targeting of different pathways [31,32].…”

Section: Introductionmentioning

confidence: 99%

Novel combinations to improve hematopoiesis in myelodysplastic syndrome

et al. 2020

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Myelodysplastic syndrome (MDS) represents a heterogeneous group of clonal hematopoietic disorders, which is characterized by cytopenias in the peripheral blood and bone marrow dysplasia due to ineffective hematopoiesis. Patients with MDS have an increased risk of transformation to acute myeloid leukemia (AML). Although the molecular basis of MDS is heterogeneous, several studies demonstrated the significant contribution of the dysregulated immune system in accelerating MDS progression. The immunosuppressive tumor microenvironment is shown to induce tolerance of MDS blasts, which may result in a further accumulation of genetic aberrations and lead to the disease progression. Increasing evidence shows an expansion of myeloid-derived suppressor cells (MDSCs), a population of inflammation-associated immature cells, in patients with MDS. Interestingly, the increased MDSC populations are shown to be correlated with a risk of disease progression in MDS. In addition, MDS is highly prevalent in aged individuals with non-hematology co-morbidities who are fragile for chemotherapy. Increasing research effort is devoting to identify novel agents to specific targeting of the MDSC population for MDS treatment.

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New therapeutic approaches in myelodysplastic syndromes: Hypomethylating agents and lenalidomide

Cited by 7 publications

References 157 publications

Noncoding RNAs and Their Response Predictive Value in Azacitidine-treated Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-related Changes

Noncoding RNAs and Their Response Predictive Value in Azacitidine-treated Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-related Changes

Introductory Chapter: Myelodysplastic Syndromes

Novel combinations to improve hematopoiesis in myelodysplastic syndrome

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