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

被引:7
|
作者
Chanias, Ioannis [1 ,2 ]
Stojkov, Kristina [1 ,2 ,3 ]
Stehle, Gregor Th. [4 ]
Daskalakis, Michael [1 ,2 ,3 ]
Simeunovic, Helena [1 ,2 ]
Njue, Linet Muthoni [1 ,2 ]
Schnegg-Kaufmann, Annatina S. [1 ,2 ,3 ]
Porret, Naomi A. [1 ,2 ]
Allam, Ramanjaneyulu [1 ,2 ,3 ]
Rao, Tata Nageswara [1 ,2 ,3 ]
Benz, Rudolf [5 ]
Ruefer, Axel [6 ,7 ]
Schmidt, Adrian [8 ]
Adler, Marcel [9 ]
Rovo, Alicia [1 ,2 ]
Balabanov, Stefan [10 ]
Stuessi, Georg [11 ]
Bacher, Ulrike [1 ]
Bonadies, Nicolas [1 ,2 ,3 ]
机构
[1] Univ Bern, Univ Hosp Bern, Dept Hematol, Inselspital, CH-3010 Bern, Switzerland
[2] Univ Bern, Univ Hosp Bern, Cent Hematol Lab, Inselspital, CH-3010 Bern, Switzerland
[3] Univ Bern, Dept BioMed Res DBMR, CH-3010 Bern, Switzerland
[4] Univ Hosp Basel, Clin Hematol, CH-4031 Basel, Switzerland
[5] Hosp Thurgau AG, Dept Hematol & Oncol, CH-8596 Muensterlingen, Switzerland
[6] Cantonal Hosp Lucerne, Dept Hematol, CH-6004 Luzern, Switzerland
[7] Cantonal Hosp Lucerne, Cent Hematol Lab, CH-6004 Luzern, Switzerland
[8] City Hosp Waid & Triemli, Clin Med Oncol & Hematol, Dept Internal Med, CH-8063 Zurich, Switzerland
[9] Hosp Thun, Ctr Med Oncol & Hematol, CH-3600 Thun, Switzerland
[10] Univ Zurich, Univ Hosp Zurich, Dept Med Oncol & Hematol, CH-8091 Zurich, Switzerland
[11] Oncol Inst Southern Switzerland, Clin Hematol, CH-6500 Bellinzona, Switzerland
关键词
myelodysplastic syndromes; postgenomic era; precision medicine; targeted therapies; future perspectives; TRANSFUSION-DEPENDENT PATIENTS; STEM-CELL TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; SOMATIC MUTATIONS IDENTIFY; CONVENTIONAL CARE REGIMENS; PROGNOSTIC SCORING SYSTEM; RANDOMIZED PHASE-III; LOW-DOSE DECITABINE; QUALITY-OF-LIFE;
D O I
10.3390/cancers13133296
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary 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.
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页数:33
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