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18 pages, 2180 KiB

Open AccessArticle

DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome—Relevance as Complementary Prognostic Biomarkers

by Ana Cristina Gonçalves, Raquel Alves, Inês Baldeiras, Bárbara Marques, Bárbara Oliveiros, Amélia Pereira, José Manuel Nascimento Costa, Emília Cortesão, Luisa Mota Vieira and Ana Bela Sarmento Ribeiro

Cancers 2021, 13(13), 3138; https://doi.org/10.3390/cancers13133138 - 23 Jun 2021

Cited by 10 | Viewed by 2559

Abstract

Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and [...] Read more.

Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total antioxidant status (TAS) and higher levels of peroxides, nitric oxide, peroxides/TAS, and 8-hydroxy-2-deoxyguanosine compared with controls. These patients had higher 5-mC levels and lower 5-hmC/5-mC ratio and LINE-1 methylation and increased methylation frequency of at least one methylated gene. Peroxide levels and peroxide/TAS ratio were higher in patients with methylated genes than those without methylation and negatively correlated with LINE-1 methylation and positively with 5-mC levels. The 5-hmC/5-mC ratio was significantly associated with progression to acute leukemia and peroxide/TAS ratio with overall survival. This study points to a relationship between oxidative stress and DNA methylation, two common pathogenic mechanisms involved in MDS, and suggests the relevance of 5-hmC/5-mC and peroxide/TAS ratios as complementary prognostic biomarkers. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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21 pages, 3126 KiB

Open AccessArticle

Low Plasma Citrate Levels and Specific Transcriptional Signatures Associated with Quiescence of CD34⁺ Progenitors Predict Azacitidine Therapy Failure in MDS/AML Patients

by Pavla Koralkova, Monika Belickova, David Kundrat, Michaela Dostalova Merkerova, Zdenek Krejcik, Katarina Szikszai, Monika Kaisrlikova, Jitka Vesela, Pavla Vyhlidalova, Jan Stetka, Alzbeta Hlavackova, Jiri Suttnar, Patrik Flodr, Jan Stritesky, Anna Jonasova, Jaroslav Cermak and Vladimir Divoky

Cancers 2021, 13(9), 2161; https://doi.org/10.3390/cancers13092161 - 30 Apr 2021

Cited by 2 | Viewed by 3028

Abstract

To better understand the molecular basis of resistance to azacitidine (AZA) therapy in myelodysplastic syndromes (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), we performed RNA sequencing on pre-treatment CD34⁺ hematopoietic stem/progenitor cells (HSPCs) isolated from 25 MDS/AML-MRC patients of the [...] Read more.

To better understand the molecular basis of resistance to azacitidine (AZA) therapy in myelodysplastic syndromes (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), we performed RNA sequencing on pre-treatment CD34⁺ hematopoietic stem/progenitor cells (HSPCs) isolated from 25 MDS/AML-MRC patients of the discovery cohort (10 AZA responders (RD), six stable disease, nine progressive disease (PD) during AZA therapy) and from eight controls. Eleven MDS/AML-MRC samples were also available for analysis of selected metabolites, along with 17 additional samples from an independent validation cohort. Except for two patients, the others did not carry isocitrate dehydrogenase (IDH)1/2 mutations. Transcriptional landscapes of the patients’ HSPCs were comparable to those published previously, including decreased signatures of active cell cycling and DNA damage response in PD compared to RD and controls. In addition, PD-derived HSPCs revealed repressed markers of the tricarboxylic acid cycle, with IDH2 among the top 50 downregulated genes in PD compared to RD. Decreased citrate plasma levels, downregulated expression of the (ATP)-citrate lyase and other transcriptional/metabolic networks indicate metabolism-driven histone modifications in PD HSPCs. Observed histone deacetylation is consistent with transcription-nonpermissive chromatin configuration and quiescence of PD HSPCs. This study highlights the complexity of the molecular network underlying response/resistance to hypomethylating agents. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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17 pages, 2334 KiB

Open AccessArticle

Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach

by Pamela Acha, Laura Palomo, Francisco Fuster-Tormo, Blanca Xicoy, Mar Mallo, Ana Manzanares, Javier Grau, Silvia Marcé, Isabel Granada, Marta Rodríguez-Luaces, María Diez-Campelo, Lurdes Zamora and Francesc Solé

Cancers 2021, 13(4), 841; https://doi.org/10.3390/cancers13040841 - 17 Feb 2021

Cited by 7 | Viewed by 4040

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, the most well characterized subtype is MDS with isolated chromosome 5q deletion (MDS del(5q)), which is the only one defined by a cytogenetic abnormality that makes these patients candidates to be [...] Read more.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, the most well characterized subtype is MDS with isolated chromosome 5q deletion (MDS del(5q)), which is the only one defined by a cytogenetic abnormality that makes these patients candidates to be treated with lenalidomide. During the last decade, single cell (SC) analysis has emerged as a powerful tool to decipher clonal architecture and to further understand cancer and other diseases at higher resolution level compared to bulk sequencing techniques. In this study, a SC approach was used to analyze intratumoral heterogeneity in four patients with MDS del(5q). Single CD34+CD117+CD45+CD19- bone marrow hematopoietic stem progenitor cells were isolated using the C1 system (Fluidigm) from diagnosis or before receiving any treatment and from available follow-up samples. Selected somatic alterations were further analyzed in SC by high-throughput qPCR (Biomark HD, Fluidigm) using specific TaqMan assays. A median of 175 cells per sample were analyzed. Inferred clonal architectures were relatively simple and either linear or branching. Similar to previous studies based on bulk sequencing to infer clonal architecture, we were able to observe that an ancestral event in one patient can appear as a secondary hit in another one, thus reflecting the high intratumoral heterogeneity in MDS del(5q) and the importance of patient-specific molecular characterization. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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21 pages, 3950 KiB

Open AccessArticle

Asian Population Is More Prone to Develop High-Risk Myelodysplastic Syndrome, Concordantly with Their Propensity to Exhibit High-Risk Cytogenetic Aberrations

by Yan Jiang, Jean-Richard Eveillard, Marie-Anne Couturier, Benoit Soubise, Jian-Min Chen, Sujun Gao, Audrey Basinko, Frédéric Morel, Nathalie Douet-Guilbert and Marie-Bérengère Troadec

Cancers 2021, 13(3), 481; https://doi.org/10.3390/cancers13030481 - 27 Jan 2021

Cited by 21 | Viewed by 3248

Abstract

This study explores the hypothesis that genetic differences related to an ethnic factor may underlie differences in phenotypic expression of myelodysplastic syndrome (MDS). First, to identify clear ethnic differences, we systematically compared the epidemiology, and the clinical, biological and genetic characteristics of MDS [...] Read more.

This study explores the hypothesis that genetic differences related to an ethnic factor may underlie differences in phenotypic expression of myelodysplastic syndrome (MDS). First, to identify clear ethnic differences, we systematically compared the epidemiology, and the clinical, biological and genetic characteristics of MDS between Asian and Western countries over the last 20 years. Asian MDS cases show a 2- to 4-fold lower incidence and a 10-year younger age of onset compared to the Western cases. A higher proportion of Western MDS patients fall into the very low- and low-risk categories while the intermediate, high and very high-risk groups are more represented in Asian MDS patients according to the Revised International Prognostic Scoring System. Next, we investigated whether differences in prognostic risk scores could find their origin in differential cytogenetic profiles. We found that 5q deletion (del(5q)) aberrations and mutations in TET2, SF3B1, SRSF2 and IDH1/2 are more frequently reported in Western MDS patients while trisomy 8, del(20q), U2AF1 and ETV6 mutations are more frequent in Asian MDS patients. Treatment approaches differ between Western and Asian countries owing to the above discrepancies, but the overall survival rate within each prognostic group is similar for Western and Asian MDS patients. Altogether, our study highlights greater risk MDS in Asians supported by their cytogenetic profile. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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21 pages, 3297 KiB

Open AccessArticle

LncRNA Profiling Reveals That the Deregulation of H19, WT1-AS, TCL6, and LEF1-AS1 Is Associated with Higher-Risk Myelodysplastic Syndrome

by Katarina Szikszai, Zdenek Krejcik, Jiri Klema, Nikoleta Loudova, Andrea Hrustincova, Monika Belickova, Monika Hruba, Jitka Vesela, Viktor Stranecky, David Kundrat, Pavla Pecherkova, Jaroslav Cermak, Anna Jonasova and Michaela Dostalova Merkerova

Cancers 2020, 12(10), 2726; https://doi.org/10.3390/cancers12102726 - 23 Sep 2020

Cited by 18 | Viewed by 3069

Abstract

Background: myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder with an incompletely known pathogenesis. Long noncoding RNAs (lncRNAs) play multiple roles in hematopoiesis and represent a new class of biomarkers and therapeutic targets, but information on their roles in MDS is limited. [...] Read more.

Background: myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder with an incompletely known pathogenesis. Long noncoding RNAs (lncRNAs) play multiple roles in hematopoiesis and represent a new class of biomarkers and therapeutic targets, but information on their roles in MDS is limited. Aims: here, we aimed to characterize lncRNAs deregulated in MDS that may function in disease pathogenesis. In particular, we focused on the identification of lncRNAs that could serve as novel potential biomarkers of adverse outcomes in MDS. Methods: we performed microarray expression profiling of lncRNAs and protein-coding genes (PCGs) in the CD34+ bone marrow cells of MDS patients. Expression profiles were analyzed in relation to different aspects of the disease (i.e., diagnosis, disease subtypes, cytogenetic and mutational aberrations, and risk of progression). LncRNA-PCG networks were constructed to link deregulated lncRNAs with regulatory mechanisms associated with MDS. Results: we found several lncRNAs strongly associated with disease pathogenesis (e.g., H19, WT1-AS, TCL6, LEF1-AS1, EPB41L4A-AS1, PVT1, GAS5, and ZFAS1). Of these, downregulation of LEF1-AS1 and TCL6 and upregulation of H19 and WT1-AS were associated with adverse outcomes in MDS patients. Multivariate analysis revealed that the predominant variables predictive of survival are blast count, H19 level, and TP53 mutation. Coexpression network data suggested that prognosis-related lncRNAs are predominantly related to cell adhesion and differentiation processes (H19 and WT1-AS) and mechanisms such as chromatin modification, cytokine response, and cell proliferation and death (LEF1-AS1 and TCL6). In addition, we observed that transcriptional regulation in the H19/IGF2 region is disrupted in higher-risk MDS, and discordant expression in this locus is associated with worse outcomes. Conclusions: we identified specific lncRNAs contributing to MDS pathogenesis and proposed cellular processes associated with these transcripts. Of the lncRNAs associated with patient prognosis, the level of H19 transcript might serve as a robust marker comparable to the clinical variables currently used for patient stratification. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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Review

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20 pages, 1790 KiB

Open AccessReview

Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes

by Syed A. Mian and Dominique Bonnet

Cancers 2021, 13(16), 4116; https://doi.org/10.3390/cancers13164116 - 16 Aug 2021

Cited by 13 | Viewed by 4825

Abstract

Myelodysplastic syndrome (MDS) are clonal haematopoietic stem cell (HSC) disorders driven by a complex combination(s) of changes within the genome that result in heterogeneity in both clinical phenotype and disease outcomes. MDS is among the most common of the haematological cancers and its [...] Read more.

Myelodysplastic syndrome (MDS) are clonal haematopoietic stem cell (HSC) disorders driven by a complex combination(s) of changes within the genome that result in heterogeneity in both clinical phenotype and disease outcomes. MDS is among the most common of the haematological cancers and its incidence markedly increases with age. Currently available treatments have limited success, with <5% of patients undergoing allogeneic HSC transplantation, a procedure that offers the only possible cure. Critical contributions of the bone marrow microenvironment to the MDS have recently been investigated. Although the better understanding of the underlying biology, particularly genetics of haematopoietic stem cells, has led to better disease and risk classification; however, the role that the bone marrow microenvironment plays in the development of MDS remains largely unclear. This review provides a comprehensive overview of the latest developments in understanding the aetiology of MDS, particularly focussing on understanding how HSCs and the surrounding immune/non-immune bone marrow niche interacts together. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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12 pages, 1215 KiB

Open AccessReview

Genetics of Myelodysplastic Syndromes

by Caner Saygin and Lucy A. Godley

Cancers 2021, 13(14), 3380; https://doi.org/10.3390/cancers13143380 - 6 Jul 2021

Cited by 10 | Viewed by 6651

Abstract

Myelodysplastic syndrome (MDS) describes a heterogeneous group of bone marrow diseases, now understood to reflect numerous germline and somatic drivers, characterized by recurrent cytogenetic abnormalities and gene mutations. Precursor conditions including clonal hematopoiesis of indeterminate potential and clonal cytopenia of undetermined significance confer [...] Read more.

Myelodysplastic syndrome (MDS) describes a heterogeneous group of bone marrow diseases, now understood to reflect numerous germline and somatic drivers, characterized by recurrent cytogenetic abnormalities and gene mutations. Precursor conditions including clonal hematopoiesis of indeterminate potential and clonal cytopenia of undetermined significance confer risk for MDS as well as other hematopoietic malignancies and cardiovascular complications. The future is likely to bring an understanding of those individuals who are at the highest risk of progression to MDS and preventive strategies to prevent malignant transformation. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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33 pages, 18661 KiB

Open AccessReview

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

by Ioannis Chanias, 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

Cancers 2021, 13(13), 3296; https://doi.org/10.3390/cancers13133296 - 30 Jun 2021

Cited by 5 | Viewed by 4684

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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19 pages, 6571 KiB

Open AccessReview

Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease

by Camilla Bertuzzo Veiga, Erin M. Lawrence, Andrew J. Murphy, Marco J. Herold and Dragana Dragoljevic

Cancers 2021, 13(8), 1968; https://doi.org/10.3390/cancers13081968 - 19 Apr 2021

Cited by 9 | Viewed by 5109

Abstract

The development of myelodysplasia syndromes (MDS) is multiphasic and can be driven by a plethora of genetic mutations and/or abnormalities. MDS is characterized by a hematopoietic differentiation block, evidenced by increased immature hematopoietic cells, termed blast cells and decreased mature circulating leukocytes in [...] Read more.

The development of myelodysplasia syndromes (MDS) is multiphasic and can be driven by a plethora of genetic mutations and/or abnormalities. MDS is characterized by a hematopoietic differentiation block, evidenced by increased immature hematopoietic cells, termed blast cells and decreased mature circulating leukocytes in at least one lineage (i.e., cytopenia). Clonal hematopoiesis of indeterminate potential (CHIP) is a recently described phenomenon preceding MDS development that is driven by somatic mutations in hemopoietic stem cells (HSCs). These mutant HSCs have a competitive advantage over healthy cells, resulting in an expansion of these clonal mutated leukocytes. In this review, we discuss the multiphasic development of MDS, the common mutations found in both MDS and CHIP, how a loss-of-function in these CHIP-related genes can alter HSC function and leukocyte development and the potential disease outcomes that can occur with dysfunctional HSCs. In particular, we discuss the novel connections between MDS development and cardiovascular disease. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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21 pages, 1333 KiB

Open AccessFeature PaperReview

Molecular Targeted Therapy in Myelodysplastic Syndromes: New Options for Tailored Treatments

by Simona Pagliuca, Carmelo Gurnari and Valeria Visconte

Cancers 2021, 13(4), 784; https://doi.org/10.3390/cancers13040784 - 13 Feb 2021

Cited by 15 | Viewed by 4334

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, progressive cytopenias and increased risk of transformation to acute myeloid leukemia. The improved understanding of the underlying biology and genetics of MDS has led to better disease and [...] Read more.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, progressive cytopenias and increased risk of transformation to acute myeloid leukemia. The improved understanding of the underlying biology and genetics of MDS has led to better disease and risk classification, paving the way for novel therapeutic opportunities. Indeed, we now have a vast pipeline of targeted agents under pre-clinical and clinical development, potentially able to modify the natural history of the diverse disease spectrum of MDS. Here, we review the latest therapeutic approaches (investigational and approved agents) for MDS treatment. A deep insight will be given to molecularly targeted therapies by reviewing new agents for individualized precision medicine. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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21 pages, 959 KiB

Open AccessReview

Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

by Bruno Fattizzo, Fabio Serpenti, Wilma Barcellini and Chiara Caprioli

Cancers 2021, 13(1), 132; https://doi.org/10.3390/cancers13010132 - 3 Jan 2021

Cited by 25 | Viewed by 8974

Abstract

Myelodysplasias with hypocellular bone marrow (hMDS) represent about 10–15% of MDS and are defined by reduced bone marrow cellularity (i.e., <25% or an inappropriately reduced cellularity for their age in young patients). Their diagnosis is still an object of debate and has not [...] Read more.

Myelodysplasias with hypocellular bone marrow (hMDS) represent about 10–15% of MDS and are defined by reduced bone marrow cellularity (i.e., <25% or an inappropriately reduced cellularity for their age in young patients). Their diagnosis is still an object of debate and has not been clearly established in the recent WHO classification. Clinical and morphological overlaps with both normo/hypercellular MDS and aplastic anemia include cytopenias, the presence of marrow hypocellularity and dysplasia, and cytogenetic and molecular alterations. Activation of the immune system against the hematopoietic precursors, typical of aplastic anemia, is reckoned even in hMDS and may account for the response to immunosuppressive treatment. Finally, the hMDS outcome seems more favorable than that of normo/hypercellular MDS patients. In this review, we analyze the available literature on hMDS, focusing on clinical, immunological, and molecular features. We show that hMDS pathogenesis and clinical presentation are peculiar, albeit in-between aplastic anemia (AA) and normo/hypercellular MDS. Two different hMDS phenotypes may be encountered: one featured by inflammation and immune activation, with increased cytotoxic T cells, increased T and B regulatory cells, and better response to immunosuppression; and the other, resembling MDS, where T and B regulatory/suppressor cells prevail, leading to genetic clonal selection and an increased risk of leukemic evolution. The identification of the prevailing hMDS phenotype might assist treatment choice, inform prognosis, and suggest personalized monitoring. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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12 pages, 688 KiB

Open AccessReview

GATA2 Related Conditions and Predisposition to Pediatric Myelodysplastic Syndromes

by Antonella Bruzzese, Davide Leardini, Riccardo Masetti, Luisa Strocchio, Katia Girardi, Mattia Algeri, Giada Del Baldo, Franco Locatelli and Angela Mastronuzzi

Cancers 2020, 12(10), 2962; https://doi.org/10.3390/cancers12102962 - 13 Oct 2020

Cited by 18 | Viewed by 6316

Abstract

Myelodysplastic syndromes (MDS) are hematopoietic disorders rare in childhood, often occurring in patients with inherited bone marrow failure syndromes or germinal predisposition syndromes. Among the latter, one of the most frequent involves the gene GATA binding protein 2 (GATA2), coding for [...] Read more.

Myelodysplastic syndromes (MDS) are hematopoietic disorders rare in childhood, often occurring in patients with inherited bone marrow failure syndromes or germinal predisposition syndromes. Among the latter, one of the most frequent involves the gene GATA binding protein 2 (GATA2), coding for a transcriptional regulator of hematopoiesis. The genetic lesion as well as the clinical phenotype are extremely variable; many patients present hematological malignancies, especially MDS with the possibility to evolve into acute myeloid leukemia. Variable immune dysfunction, especially resulting in B- and NK-cell lymphopenia, lead to severe infections, including generalized warts and mycobacterial infection. Defects of alveolar macrophages lead to pulmonary alveolar proteinosis through inadequate clearance of surfactant proteins. Currently, there are no clear guidelines for the monitoring and treatment of patients with GATA2 mutations. In patients with MDS, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT) that restores normal hematopoiesis preventing the progression to acute myeloid leukemia and clears long-standing infections. However, to date, the donor type, conditioning regimen, and the optimal time to proceed to HSCT, as well as the level of chimerism needed to reverse the phenotype, remain unclear highlighting the need for consensus guidelines. Full article

(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndrome)

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