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Review

Myelodysplastic Syndromes in the Postgenomic Era and Future Perspectives for Precision Medicine

1
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
2
Department for BioMedical Research (DBMR), University of Bern, 3010 Bern, Switzerland
3
Clinic of Hematology, University Hospital Basel, 4031 Basel, Switzerland
4
Department of Hematology and Oncology, Hospital Thurgau AG, 8596 Muensterlingen, Switzerland
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Department of Hematology and Central Hematology Laboratory, Cantonal Hospital Lucerne, 6004 Lucerne, Switzerland
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Department of Internal Medicine, Clinic of Medical Oncology and Hematology, City Hospital Waid and Triemli, 8063 Zurich, Switzerland
7
Center for Medical Oncology and Hematology, Hospital Thun, 3600 Thun, Switzerland
8
Department of Medical Oncology and Hematology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland
9
Clinic of Hematology, Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Adriano Venditti
Cancers 2021, 13(13), 3296; https://doi.org/10.3390/cancers13133296
Received: 14 May 2021 / Revised: 18 June 2021 / Accepted: 21 June 2021 / Published: 30 June 2021
(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)
With demographic ageing, improved cancer survivorship and increased diagnostic sensitivity, incident cases of patients with Myelodysplastic Syndromes (MDS) are continuously rising, leading to a relevant impact on health care resources. Disease heterogeneity and various comorbidities are challenges for the management of the generally elderly patients. Therefore, experienced physicians and multidisciplinary teams should be involved in the establishment of the correct diagnosis, risk-assessment and personalized treatment plan. Next-generation sequencing allows for early detection of clonal hematopoiesis and monitoring of clonal evolution, but also poses new challenges for its appropriate use. At present, allogeneic hematopoietic stem cell transplantation remains the only curative treatment option for a minority of fit MDS patients. All others receive palliative treatment and will eventually progress, having an unmet need for novel therapies. Targeting compounds are in prospect for precision medicine, however, abrogation of clonal evolution to acute myeloid leukemia remains actually out of reach.
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders caused by sequential accumulation of somatic driver mutations in hematopoietic stem and progenitor cells (HSPCs). MDS is characterized by ineffective hematopoiesis with cytopenia, dysplasia, inflammation, and a variable risk of transformation into secondary acute myeloid leukemia. The advent of next-generation sequencing has revolutionized our understanding of the genetic basis of the disease. Nevertheless, the biology of clonal evolution remains poorly understood, and the stochastic genetic drift with sequential accumulation of genetic hits in HSPCs is individual, highly dynamic and hardly predictable. These continuously moving genetic targets pose substantial challenges for the implementation of precision medicine, which aims to maximize efficacy with minimal toxicity of treatments. In the current postgenomic era, allogeneic hematopoietic stem cell transplantation remains the only curative option for younger and fit MDS patients. For all unfit patients, regeneration of HSPCs stays out of reach and all available therapies remain palliative, which will eventually lead to refractoriness and progression. In this review, we summarize the recent advances in our understanding of MDS pathophysiology and its impact on diagnosis, risk-assessment and disease monitoring. Moreover, we present ongoing clinical trials with targeting compounds and highlight future perspectives for precision medicine. View Full-Text
Keywords: myelodysplastic syndromes; postgenomic era; precision medicine; targeted therapies; future perspectives myelodysplastic syndromes; postgenomic era; precision medicine; targeted therapies; future perspectives
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MDPI and ACS Style

Chanias, I.; Stojkov, K.; Stehle, G.T.; Daskalakis, M.; Simeunovic, H.; Njue, L.M.; Schnegg-Kaufmann, A.S.; Porret, N.A.; Allam, R.; Rao, T.N.; Benz, R.; Ruefer, A.; Schmidt, A.; Adler, M.; Rovo, A.; Balabanov, S.; Stuessi, G.; Bacher, U.; Bonadies, N., on behalf of the Swiss MDS Study Group. Myelodysplastic Syndromes in the Postgenomic Era and Future Perspectives for Precision Medicine. Cancers 2021, 13, 3296. https://doi.org/10.3390/cancers13133296

AMA Style

Chanias I, Stojkov K, Stehle GT, Daskalakis M, Simeunovic H, Njue LM, Schnegg-Kaufmann AS, Porret NA, Allam R, Rao TN, Benz R, Ruefer A, Schmidt A, Adler M, Rovo A, Balabanov S, Stuessi G, Bacher U, Bonadies N on behalf of the Swiss MDS Study Group. Myelodysplastic Syndromes in the Postgenomic Era and Future Perspectives for Precision Medicine. Cancers. 2021; 13(13):3296. https://doi.org/10.3390/cancers13133296

Chicago/Turabian Style

Chanias, Ioannis, Kristina Stojkov, Gregor Th. Stehle, Michael Daskalakis, Helena Simeunovic, Linet Muthoni Njue, Annatina S. Schnegg-Kaufmann, Naomi A. Porret, Ramanjaneyulu Allam, Tata Nageswara Rao, Rudolf Benz, Axel Ruefer, Adrian Schmidt, Marcel Adler, Alicia Rovo, Stefan Balabanov, Georg Stuessi, Ulrike Bacher, and Nicolas Bonadies on behalf of the Swiss MDS Study Group. 2021. "Myelodysplastic Syndromes in the Postgenomic Era and Future Perspectives for Precision Medicine" Cancers 13, no. 13: 3296. https://doi.org/10.3390/cancers13133296

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