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Recent Advances in Myelodysplastic Syndromes: Diagnosis, Prognosis and Clinical Therapy
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Recent Advances in Myelodysplastic Syndromes: Diagnosis, Prognosis and Clinical Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (1 November 2023) | Viewed by 10704

Special Issue Editor

Dr. Thomas Schroeder

E-Mail Website
Guest Editor
Department of Hematology and Stem Cell Transplantation, University Hospital Essen, West German Cancer Center, 45147 Essen, Germany
Interests: myelodysplastic syndromes; cancer therapy

Special Issue Information

Dear Colleagues, 

Myelodysplastic syndromes (MDS) are a heterogenous group of clonal blood stem cell disorders, which mainly affect older patients and are characterized by hematopoietic insufficiency as well as an increased propensity for the development of secondary acute myeloid leukemia (sAML). While in early phases of the disease treatment approaches aim to improve ineffective hematopoiesis, the treatment goal in advanced phases is to prolong survival or even eradicate the disease by allogeneic stem cell transplantation (allo-SCT), with the latter representing the only curative option to date. For a long time, MDS have been considered to be hematopoietic-cell autonomous diseases originating from the accumulation of genetic and epigenetic alterations within the hematopoietic stem and progenitor cell (HSPC) population. Recently, it has become apparent that these myeloid disorders do not exclusively arise from HSPC but also involve the entire bone marrow microenvironment.  Although understanding the complexity of the underlying mechanisms driving the disease still represents a challenge, elucidation of these processes begins to translate into our clinical day life. In this special issue we highlight recent advances in our understanding of the MDS pathophysiology and how this is integrated into novel diagnostic and therapeutic approaches.

Dr. Thomas Schroeder
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • myelodysplatics syndromes
  • ineffective hematopoiesis
  • mutations
  • bone marrow microenvironment
  • allogeneic stem cell transplantation
  • diagnostic

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Published Papers (5 papers)

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Research

14 pages, 6258 KiB  
Article
Development of MDS in Pediatric Patients with GATA2 Deficiency: Increased Histone Trimethylation and Deregulated Apoptosis as Potential Drivers of Transformation
by Franziska Schreiber, Guido Piontek, Yuki Schneider-Kimoto, Stephan Schwarz-Furlan, Rita De Vito, Franco Locatelli, Carole Gengler, Ayami Yoshimi, Andreas Jung, Frederick Klauschen, Charlotte M. Niemeyer, Miriam Erlacher and Martina Rudelius
Cancers 2023, 15(23), 5594; https://doi.org/10.3390/cancers15235594 - 26 Nov 2023
Cited by 2 | Viewed by 1606
Abstract
GATA2 deficiency is a heterogeneous, multisystem disorder associated with a high risk of developing myelodysplastic syndrome (MDS) and the progression to acute myeloid leukemia. The mechanisms underlying malignant transformation in GATA2 deficiency remain poorly understood, necessitating predictive markers to assess an individual’s risk [...] Read more.
GATA2 deficiency is a heterogeneous, multisystem disorder associated with a high risk of developing myelodysplastic syndrome (MDS) and the progression to acute myeloid leukemia. The mechanisms underlying malignant transformation in GATA2 deficiency remain poorly understood, necessitating predictive markers to assess an individual’s risk of progression and guide therapeutic decisions. In this study, we performed a systematic analysis of bone marrow biopsies from 57 pediatric MDS patients. Focusing on hematopoiesis and the hematopoietic niche, including its microenvironment, we used multiplex immunofluorescence combined with multispectral imaging, gene expression profiling, and multiplex RNA in situ hybridization. Patients with a GATA2 deficiency exhibited a dysregulated GATA2 transcriptional network. Disease progression (GATA2-EB, n = 6) was associated with increased GATA2 mRNA levels, restored expression of the GATA2 target EZH2, and increased H3K27me3. GATA2-EB was further characterized by the high expression of the anti-apoptotic protein BCL2, a feature absent in children with a GATA2 deficiency and refractory cytopenia of childhood (GATA2-RCC, n = 24) or other pediatric MDS subgroups (RCC, n = 17; MDS-EB, n = 10). The multispectral imaging analysis of additional BCL2 family members revealed significantly elevated Mediators of Apoptosis Combinatorial (MAC) scores in GATA2-EB patients. Taken together, our findings highlight the potential drivers of disease progression in GATA2 deficiency, particularly increased histone trimethylation and dysregulated apoptosis. Furthermore, upregulated BCL2 and EZH2 and increased MAC scores provide a strong rationale for the use of venetoclax and azacitidine in therapeutic regimens for GATA2-EB. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndromes: Diagnosis, Prognosis and Clinical Therapy)
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14 pages, 2991 KiB  
Article
A Personalized Risk Model for Azacitidine Outcome in Myelodysplastic Syndrome and Other Myeloid Neoplasms Identified by Machine Learning Model Utilizing Real-World Data
by Kirsty Sharplin, William Proudman, Rakchha Chhetri, Elizabeth Ngoc Hoa Tran, Jamie Choong, Monika Kutyna, Philip Selby, Aidan Sapio, Oisin Friel, Shreyas Khanna, Deepak Singhal, Michelle Damin, David Ross, David Yeung, Daniel Thomas, Chung H. Kok and Devendra Hiwase
Cancers 2023, 15(16), 4019; https://doi.org/10.3390/cancers15164019 - 8 Aug 2023
Cited by 1 | Viewed by 1527
Abstract
Azacitidine is an approved therapy for higher-risk myelodysplastic syndrome (MDS). However, only 30–40% patients respond to azacitidine, and the responses may take up to six cycles to become evident. Delayed responses and the myelosuppressive effects of azacitidine make it challenging to predict which [...] Read more.
Azacitidine is an approved therapy for higher-risk myelodysplastic syndrome (MDS). However, only 30–40% patients respond to azacitidine, and the responses may take up to six cycles to become evident. Delayed responses and the myelosuppressive effects of azacitidine make it challenging to predict which patients will benefit. This is further compounded by a lack of uniform prognostic tools to identify patients at risk of early treatment failure. Hence, we performed a retrospective analysis of 273 consecutive azacytidine-treated patients. The median overall survival was 16.25 months with only 9% alive at 5 years. By using pre-treatment variables incorporated into a random forest machine learning model, we successfully identified those patients unlikely to benefit from azacytidine upfront (7.99 vs. 22.8 months, p < 0.0001). This model also identified those who required significantly more hospitalizations and transfusion support. Notably, it accurately predicted survival outcomes, outperforming the existing prognostic scoring system. By integrating somatic mutations, we further refined the model and identified three distinct risk groups with significant differences in survival (5.6 vs. 10.5 vs. 43.5 months, p < 0.0001). These real-world findings emphasize the urgent need for personalized prediction tools tailored to hypomethylating agents, reducing unnecessary complications and resource utilization in MDS treatment. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndromes: Diagnosis, Prognosis and Clinical Therapy)
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13 pages, 2854 KiB  
Article
Usefulness of New Neutrophil-Related Hematologic Parameters in Patients with Myelodysplastic Syndrome
by Iwona Kwiecień, Elżbieta Rutkowska, Krzysztof Gawroński, Katarzyna Kulik, Alicja Dudzik, Agata Zakrzewska, Agata Raniszewska, Waldemar Sawicki and Piotr Rzepecki
Cancers 2023, 15(9), 2488; https://doi.org/10.3390/cancers15092488 - 26 Apr 2023
Cited by 5 | Viewed by 1959
Abstract
Myelodysplastic syndromes (MDS) are common malignant disorders with a poor prognosis. It is necessary to search for new rapid diagnostic methods to detect MDS patients with cytogenetic changes. The aim of the study was to assess new hematological neutrophil- and monocyte- related parameters [...] Read more.
Myelodysplastic syndromes (MDS) are common malignant disorders with a poor prognosis. It is necessary to search for new rapid diagnostic methods to detect MDS patients with cytogenetic changes. The aim of the study was to assess new hematological neutrophil- and monocyte- related parameters I then bone marrow of MDS patient with and without cytogenetic changes. A total of 45 patients with MDS, including 17 patients with cytogenetic changes, were examined. The study was conducted using the Sysmex XN-Series hematological analyzer. New neutrophil and monocyte parameters, such as immature granulocytes (IG), neutrophil reactivity intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), neutrophil size (NE-FSC) and neutrophil/monocyte data relating to granularity, activity and volume (NE-WX/MO-WX, NE-WY/MO-WY, NE-WZ/MO-WZ, MO-X, MO-Y, MO-Z) were evaluated. We observed higher median proportions of NE-WX, NE-WY, NE-WZ, and IG counts in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The NE-FSC parameter was lower in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The combination of new neutrophil parameters was found to be a new successful approach in distinguishing MDS patients with cytogenetic changes from patients without cytogenetic changes. It appears that there may be unique neutrophil parameter signatures associated with an underlying mutation. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndromes: Diagnosis, Prognosis and Clinical Therapy)
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11 pages, 1273 KiB  
Article
Clinical and Cytogenetic Characterization of Early and Late Relapses in Patients Allografted for Myeloid Neoplasms with a Myelodysplastic Component
by Victoria Platte, Anika Bergmann, Barbara Hildebrandt, Dagmar Wieczorek, Esther Schuler, Ulrich Germing, Jennifer Kaivers, Rainer Haas, Guido Kobbe, Thomas Schroeder and Christina Rautenberg
Cancers 2022, 14(24), 6244; https://doi.org/10.3390/cancers14246244 - 18 Dec 2022
Cited by 2 | Viewed by 1594
Abstract
An improved understanding of relapse kinetics is required to optimize detection and treatment strategies for the post-transplant relapse of myeloid neoplasms. Therefore, we retrospectively analyzed data from 91 patients allografted for MDS (n = 54), AML-MRC (n = 29) and chronic [...] Read more.
An improved understanding of relapse kinetics is required to optimize detection and treatment strategies for the post-transplant relapse of myeloid neoplasms. Therefore, we retrospectively analyzed data from 91 patients allografted for MDS (n = 54), AML-MRC (n = 29) and chronic myelomonocytic leukemia (CMML, n = 8), who relapsed after transplant. Patients with early (<12 months, n = 56) and late relapse (>12 months, n = 35) were compared regarding patient-, disease- and transplant-related factors, including karyotype analyses at diagnosis and relapse. After a median follow-up of 17.4 months after relapse, late relapses showed improved outcomes compared with early relapses (2-yr OS 67% vs. 32%, p = 0.0048). Comparing frequency of distinct patient-, disease- and transplant-related factors among early and late relapses, complex karyotype (p = 0.0004) and unfavorable disease risk at diagnosis (p = 0.0008) as well as clonal evolution at relapse (p = 0.03) were more common in early than in late relapses. Furthermore, patients receiving transplant without prior cytoreduction or in complete remission were more frequently present in the group of late relapses. These data suggest that cytogenetics rather than disease burden at diagnosis and transplant-related factors determine the timepoint of post-transplant relapse and that upfront transplantation may be favored in order to delay relapse. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndromes: Diagnosis, Prognosis and Clinical Therapy)
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11 pages, 608 KiB  
Article
Assessing the Prognosis of Patients with Myelodysplastic Syndromes (MDS)
by Annika Kasprzak, Kathrin Nachtkamp, Norbert Gattermann and Ulrich Germing
Cancers 2022, 14(8), 1941; https://doi.org/10.3390/cancers14081941 - 12 Apr 2022
Cited by 9 | Viewed by 3169
Abstract
Prognostic stratification in patients with myelodysplastic syndrome (MDS) relies on a number of key factors. Combining such patient-related and disease-related prognostic parameters into useful assessment tools remains a challenge. The most widely used scoring systems include the international prognostic scoring system (IPSS), the [...] Read more.
Prognostic stratification in patients with myelodysplastic syndrome (MDS) relies on a number of key factors. Combining such patient-related and disease-related prognostic parameters into useful assessment tools remains a challenge. The most widely used scoring systems include the international prognostic scoring system (IPSS), the revised IPSS (IPSS-R), the World Health Organization (WHO) Prognostic Scoring System (WPSS), and the new molecular IPSS (IPSS-M). Similar to the IPSS-R and the IPSS-M, the chronic myelomonocytic leukemia (CMML) prognostic scoring system (CPSS) and the CPSS molecular (CPSS-mol) are powerful and reliable prognostic tools that help to assess the individual prognosis of patients with CMML. The well-established prognostic assessment of MDS and CMML may be further augmented by additional disease-related parameters, such as somatic mutations, or patient-related factors, such as comorbidities. In this article, we briefly describe useful prognostic scoring systems for myelodysplastic syndromes and identify some open questions that require further investigation. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndromes: Diagnosis, Prognosis and Clinical Therapy)
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