Targeted therapies for myelodysplastic Syndromes/Neoplasms (MDS): current landscape and future directions.

INTRODUCTION: Myelodysplastic syndromes/neoplasms (MDS) are a heterogeneous group of hematologic malignancies that are stratified into high-risk (HR-MDS) and low-risk (LR-MDS) categories. Until recently LR-MDS has been typically managed by supportive measures and erythropoiesis-stimulating agents (ESAs); whereas, management of HR-MDS, typically included hypomethylating agents and allogeneic hematopoietic stem cell transplant. However, the limited rates and duration of response observed with these interventions prompted the search for targeted therapies to improve the outcomes among patients with MDS. AREAS COVERED: Here we review the current landscape of targeted therapies in MDS. These include pyruvate kinase and hypoxia-inducible factor (HIF) activators; TGF-beta, telomerase, BCL2 and isocitrate dehydrogenase (IDH) inhibitors; as well as novel approaches targeting inflammation, pyroptosis, immune evasion and RNA splicing machinery. EXPERT OPINION: This review highlights the progress and challenges in MDS treatment. Despite some promising results, many therapies remain in early development or have faced setbacks, emphasizing the need for a more comprehensive understanding of the disease's pathobiology. Continued research into targeted therapies, homogenous clinical trial designs, as well as increased incorporation of molecular prognostic tools and artificial intelligence into trial design are essential for developing effective treatments for MDS and improving patient outcomes.

Ferroptosis: a new mechanism of traditional Chinese medicine for treating hematologic malignancies.

Ferroptosis is a recently identified form of cell death characterized by lipid peroxidation and elevated iron levels. It is closely associated with hematologic malignancies, including leukemia, multiple myeloma (MM), and myelodysplastic syndromes (MDS). Research indicates that ferroptosis could represent a novel therapeutic target for these hematologic malignancies. Furthermore, traditional Chinese medicine (TCM) has been shown to modulate hematologic malignancies through the ferroptosis pathway. This paper aims to elucidate the mechanisms underlying ferroptosis and summarize the current research advancements regarding ferroptosis in hematologic malignancies, as well as the role of traditional Chinese medicine in the prevention and treatment of ferroptosis, with the goal of enhancing treatment efficacy.

Measurable residual disease assessment prior to allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndromes: a 20-year monocentric study.

Patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who undergo allogeneic hematopoietic stem-cell transplantation (alloHSCT) can have divergent survival outcomes while all in morphological complete remission (CR). Techniques of measurable residual disease (MRD) have allowed us to refine their prognosis in two categories: MRD-positive and MRD-negative patients. We conducted a monocentric retrospective study (01/2000-12/2020) to assess the prognosis of pretransplant MRD status measured by multiparametric flow cytometry (MFC) and molecular biology assessed by PCR. 192 patients were included. The median follow-up period was 77 months. Among patients undergoing alloHSCT in CR, overall survival (median-OS: 130.6 vs. 16.0 months, P < 0.001), disease-free survival (median-DFS: 109.6 vs. 7.1 months, P < 0.001) and cumulative incidence of relapse (12-month CIR: 7.3% vs. 33.7%, P < 0.0001) were significantly different between MRD-negative and MRD-positive patients. Patients with discordant intermethod results had intermediate DFS. MRD-negative patients according to molecular PCR-based techniques, WT1 overexpression and MFC had longer median-DFS, compared to MRD-positive patients (P = 0.001, P < 0.001, P < 0.001, respectively). Looking into subgroups, MRD-positive patients among the ELN2017 adverse-category (P < 0.0001), myeloablative and reduced-intensity conditioning regimens (P < 0.0001, P = 0.005), < 60-year patients (P < 0.001) and AML patients (P < 0.001) were associated with lower DFS. This difference was not found in ≥ 60-year patients (P = 0.27) and MDS patients (P = 0.70). MRD-positive patients within the favorable/intermediate ELN2017 category trended toward lower DFS (P = 0.05). We confirmed that MRD status prior to alloHSCT is a strong prognostic factor for OS, DFS and CIR. Combining MFC and molecular-PCR techniques to assess MRD seems primordial as inter-method discordance can be consequential.

The immunobiology of myelodysplastic neoplasms: a mini-review.

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing clinical outcomes and survival for patients with MDS.

[Aberrant mitochondrial dynamics in myeloid neoplasms].

Age-related clonal hematopoiesis and myeloid malignancies arise from hematopoietic stem cells and progenitors with genetic abnormalities. Advances in next-generation sequencing technology have led to the identification of a wide variety of genetic alterations involved in disease onset. However, it remains unclear how diverse genetic alterations, lacking disease specificity, lead to the development of myeloid malignancies and the progression of clonal hematopoiesis. Mitochondrial abnormalities and their roles in various pathological conditions such as aging, inflammation, neurological diseases, cardiac diseases, and cancer have recently been revealed, and have garnered attention as new therapeutic targets. This review focuses on regulation of mitochondrial dynamics and outlines the role of mitochondria in myeloid malignancies and clonal hematopoiesis.

Identification of novel myelodysplastic syndromes prognostic subgroups by integration of inflammation, cell-type composition, and immune signatures in the bone marrow.

Mutational profiles of myelodysplastic syndromes (MDS) have established that a relatively small number of genetic aberrations, including SF3B1 and SRSF2 spliceosome mutations, lead to specific phenotypes and prognostic subgrouping. We performed a multi-omics factor analysis (MOFA) on two published MDS cohorts of bone marrow mononuclear cells (BMMNCs) and CD34 + cells with three data modalities (clinical, genotype, and transcriptomics). Seven different views, including immune profile, inflammation/aging, retrotransposon (RTE) expression, and cell-type composition, were derived from these modalities to identify the latent factors with significant impact on MDS prognosis. SF3B1 was the only mutation among 13 mutations in the BMMNC cohort, indicating a significant association with high inflammation. This trend was also observed to a lesser extent in the CD34 + cohort. Interestingly, the MOFA factor representing the inflammation shows a good prognosis for MDS patients with high inflammation. In contrast, SRSF2 mutant cases show a granulocyte-monocyte progenitor (GMP) pattern and high levels of senescence, immunosenescence, and malignant myeloid cells, consistent with their poor prognosis. Furthermore, MOFA identified RTE expression as a risk factor for MDS. This work elucidates the efficacy of our integrative approach to assess the MDS risk that goes beyond all the scoring systems described thus far for MDS.

Distinct mutation features and its clinical significance in myelodysplastic syndromes with normal karyotype.

Myelodysplastic syndromes (MDS) is a highly heterogeneous myeloid neoplastic disease, which needs personalized evaluation and therapy. To analyze the features and significance of gene mutations for MDS patients with normal karyotype (NK) at diagnosis, targeted sequencing was conducted on 616 MDS patients with NK, alongside 457 MDS cases with abnormal karyotype (AK). The results showed that the incidence of somatic mutation reached 70.3% and 83.8% in the NK and AK group, respectively. Initial mutation including ASXL1, DNMT3A and TET2 were common in NK group, which is the same as AK group. Some karyotype-associated gene mutations, such as TP53 and U2AF1, were relatively rare in NK group. Moreover, 34 out of 91 samples who progressed to acute myeloid leukemia (AML) underwent repeat sequencing during follow-up. 25 cases were checked out with newly emerged mutations. The AML-associated genetic alterations mainly involved with active signaling and transcription factors. In patients with NK, serial targeted sequencing was employed for minimal residual disease (MRD) monitoring, indicating the efficacy and relapse of the patients. In summary, MDS with NK showed distinct mutation features from those with AK. High-frequency gene mutations together with the mutational evolution suggested the diagnostic and monitoring significance of next generation sequencing for NK-MDS.

A Mysterious Rash Following Cardiothoracic Surgery: A Not So Sweet Ending.

A male in his 70s, with a recent history of aortic valve replacement, mitral valve repair, and permanent pacemaker implantation (PPM), developed a fever, raised inflammatory markers, and a disseminated rash. Despite being attributed a diagnosis of an unspecified connective tissue disorder and erythema nodosum at his local hospital, his symptoms continued to deteriorate. A subsequent urgent admission was arranged to his original cardiothoracic centre for the exclusion of infective endocarditis (IE). Although this was subsequently ruled out by echocardiography and microbiological evaluation, a diagnosis of Sweet syndrome (SS) was made following a punch biopsy of a skin lesion. This was later attributed to myelodysplastic syndrome following a bone marrow biopsy. In this report, we firstly describe our diagnostic algorithm for reaching this diagnosis and the characteristic skin lesions associated with this condition. We furthermore review the history of SS, its known associations, and treatment options.

[Long-term hypomethylating agents in patients with myelodysplastic syndromes: a multi-center retrospective study].

Objective: To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) . Methods: A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results: Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype (P=0.02, OR=0.39, 95%CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation (P=0.02, OR=0.22, 95%CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95%CI 21.14-30.19) months. HMA response (P=0.036, HR=0.47, 95%CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype (P=0.024, HR=2.14, 95%CI 1.10-4.15) , leukemia transformation (P<0.001, HR=2.839, 95%CI 1.64-4.92) , and TP53 mutation (P=0.012, HR=2.19, 95%CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion: Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Real-World Study of the Burden of Myelodysplastic Syndromes in Patients and Their Caregivers in Europe and the United States.

INTRODUCTION: Myelodysplastic syndromes (MDS) are characterized by bone marrow failure, peripheral blood cytopenias and a high risk of progression to acute myeloid leukemia (AML), which is associated with a poor prognosis and low survival rates. This study combined surveys with patient chart reviews to document real-world clinical practice and burden of MDS, including perspectives of physicians, patients and caregivers and underlying discrepancies. METHODS: Physicians in major European countries and the US provided information on 1445 patients, stratified into lower- (LR) and higher-risk (HR) MDS. Patients had the opportunity to complete questionnaires describing the impact of MDS. Caregivers had the option to report on the burden of caring for a patient with MDS. RESULTS: While supportive treatment was common, mainly with erythropoietins (52%), anti-AML agents were more frequently used in HR than in LR patients (70% vs 20%), while HR patients generally received more transfusions (48% vs 36%). Symptoms with the largest discordance between patient vs physician reporting were excessive bruising (30% vs 14%), GI side effects (19% vs 6%) and feeling tired or fatigued (68% vs 56%). A bigger impact of fatigue was reported on the European Organization for the Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for HR vs LR patients (43.2 vs 36.5 on a scale from 0 to 100). There was discordance between caregivers vs physicians on reporting of weekly caregiver hours (45.4 vs 29.2) with a Zarit Burden Interview score (ZBI, score 0-88) of 25.4. CONCLUSIONS: Patients reported a higher frequency than their physicians of top symptoms, with MDS-related disruptions in daily life for both patients and caregivers. There is a need for new therapeutic strategies, along with shared understanding and decision making among patients, caregivers and physicians, to optimize disease management and improve quality of life in people living with MDS.

Case report: Development of clonal hematologic disorders from inherited bone marrow failure.

Introduction: Inherited bone marrow failure (IBMF) syndromes are caused by mutations forming pathologic germline variants resulting in the production of defective hematopoietic stem cells (HSC) and in congenital failure in the production of one or more blood lineages. An acquisition of subsequent somatic mutations is determining further course of the disease. Nevertheless, a certain number of patients with IBMF may escape correct diagnosis in childhood, especially those with mild cytopenia and minimal clinical features without non-hematologic symptoms. These patients usually present in the third decade of life with unexplained cytopenia or myelodysplastic syndrome (MDS). Methods and results: We report 2 patients with IBMF who were correctly diagnosed between 20 and 40 years of age when they were referred with progressive MDS with adverse prognostic factors that affected their outcome. Discussion: IBMF syndromes should be excluded in all patients below 40 years of age with unexplained cytopenia. Early hematopoietic stem cell transplantation (HSCT) is the treatment of choice in these patients.

RNA methylation sequencing shows different gene expression signatures for response to azacytidine therapy in high-grade myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are myeloid malignancies with heterogeneous genotypes and phenotypes, characterized by ineffective haematopoiesis and a high risk of progression towards acute myeloid leukaemia (AML). Prognosis for patients treated with hypomethylating agents (HMAs), as is azacytidine, the main drug used as frontline therapy for MDS is mostly based on cytogenetics and next generation sequencing (NGS) of the initial myeloid clone. Although the critical influence of the epigenetic landscape upon cancer cells survival and development as well on tumour environment establishment is currently recognized and approached within current clinical practice in MDS, the heterogenous response of the patients to epigenetic therapy is suggesting a more complex mechanism of action, as is the case of RNA methylation. In this sense, the newly emerging field of epitranscriptomics could provide a more comprehensive perspective upon the modulation of gene expression in malignancies, as is the proof-of-concept of MDS. We initially did RNA methylation sequencing on MDS patients (n = 6) treated with azacytidine and compared responders with non-responders. Afterwards, the genes identified were assessed in vitro and afterwards validated on a larger cohort of MDS patients treated with azacytidine (n = 58). Our data show that a more accurate prognosis could be based on analysing the methylome and thus we used methylation sequencing to differentially split high-grade MDS patients with identical demographical and cytogenetic features, between azacytidine responders and non-responders.

How we diagnose Myelodysplastic syndromes.

The Myelodysplastic syndromes (MDS) are a heterogenous group of clonal bone marrow (BM) stem cell myeloid neoplasms, characterized by ineffective hematopoiesis that results in dysplasia in hematopoietic cells and peripheral cytopenias, especially anemia, and a propensity to leukemic transformation. The suspicion of MDS is raised by a typical but not specific clinical picture and routine laboratory findings, but the gold standard for MDS diagnosis is still BM examination with the presence of uni-or multi-lineage dysplasia and increased blast percentage, together with exclusion of other reasons. Cytogenetics is also an essential part of the diagnostic and prognostic processes. Flow cytometry and full genetic characterization are helpful but not mandatory for MDS diagnosis. This review summarizes the current steps of diagnostic approach for a patient suspected of having MDS. We also express our hopes that within the near future, non-invasive technologies, especially digital and peripheral blood genetics, will mature and be introduced into practice.

Mesenchymal Stem Cells in Myelodysplastic Syndromes and Leukaemia.

Mesenchymal stem cells (MSCs) are one of the main residents in the bone marrow (BM) and have an essential role in the regulation of haematopoietic stem cell (HSC) differentiation and proliferation. Myelodysplastic syndromes (MDSs) are a group of myeloid disorders impacting haematopoietic stem and progenitor cells (HSCPs) that are characterised by BM failure, ineffective haematopoiesis, cytopenia, and a high risk of transformation through the expansion of MDS clones together with additional genetic defects. It has been indicated that MSCs play anti-tumorigenic roles such as in cell cycle arrest and pro-tumorigenic roles including the induction of metastasis in MDS and leukaemia. Growing evidence has shown that MSCs have impaired functions in MDS, such as decreased proliferation capacity, differentiation ability, haematopoiesis support, and immunomodulation function and increased inflammatory alterations within the BM through some intracellular pathways such as Notch and Wnt and extracellular modulators abnormally secreted by MSCs, including increased expression of inflammatory factors and decreased expression of haematopoietic factors, contributing to the development and progression of MDSs. Therefore, MSCs can be targeted for the treatment of MDSs and leukaemia. However, it remains unclear what drives MSCs to behave abnormally. In this review, dysregulations in MSCs and their contributions to myeloid haematological malignancies will be discussed.

Treatment characteristics and outcomes in lower-risk, non-del(5q) myelodysplastic syndromes: findings from a medical record review in the USA, Canada and Europe.

Aim: To assess treatment patterns and outcomes in patients with non-del(5q) lower-risk myelodysplastic syndromes. Methods: Patient medical records were reviewed in the USA, Canada (CAN), UK and the EU. Results: Analysis included 119 patients in the USA/CAN (median age, 61.5 years) and 245 patients in the UK/EU (median age, 67.3 years). Most patients received erythropoiesis-stimulating agents (ESAs) as first-line (1L) therapy (USA/CAN: 89.0%; UK/EU: 90.2%). A substantial proportion of 1L erythropoiesis-stimulating agent-treated patients were transfusion dependent before 1L (USA/CAN: 37.1%; UK/EU: 51.2%); a small percentage of these patients achieved transfusion independence during 1L therapy (USA/CAN: 2.8%; UK/EU: 14.4%). Conclusion: These findings highlight an unmet need for more effective treatments among patients with non-del(5q) lower-risk myelodysplastic syndromes.

[Box: see text].

WHO/ICC Classification for Myelodysplastic Neoplasms/Syndromes Performs Better for Subtype Cytomorphological Diagnosis?

The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (ICC) and the 5th edition of the WHO classification (WHO 2022) have refined the diagnosis of myelodysplastic syndromes (MDS). Both classifications segregate MDS subtypes based on molecular or cytogenetic findings but rely on the subjective assessment of blast cell percentage and dysplasia in hematopoietic cell lineages. This study aimed to evaluate interobserver concordance among 13 cytomorphologists from eight hospitals in assessing blast percentages and dysplastic features in 44 MDS patients. The study found fair interobserver agreement for the PB blast percentage and moderate agreement for the BM blast percentage, with the best concordance in cases with <5% BM blasts and >10% BM blasts. Monocyte count agreement was fair, and dysplasia assessment showed moderate concordance for megakaryocytic lineage but lower concordance for erythroid and granulocytic lineages. Overall, interobserver concordance for MDS subtypes was moderate across all classifications, with slightly better results for WHO 2022. These findings highlight the ongoing need for morphological evaluation in MDS diagnosis despite advances in genetic and molecular techniques. The study supports the blast percentage ranges established by the ICC but suggests refining BM blast cutoffs. Given the moderate interobserver concordance, a unified classification approach for MDS is recommended.

Screening of Myelodysplastic Syndromes Using Research Parameters of Complete Blood Count: Automated Detection of Dysplasia.

Myelodysplastic syndromes (MDS) present with polymorphic and non-specific diagnostic features Research parametersfrom hematology analyzers may be useful to discriminate MDS-related cytopenia.Parameters such as Neu X (related to the cytoplasmic complexity) and Neu Y (related to nucleic acid content) show promise to detect dysplasia of MDS and aid to recognize MDS from cytopenias of other etiologies.

Patients' perspectives on oral decitabine/cedazuridine for the treatment of myelodysplastic syndromes/neoplasms.

Background: Hypomethylating agents (HMAs) are guideline-recommended treatment for higher-risk myelodysplastic syndromes/neoplasms (MDS). However, a prior survey of patients with MDS reported challenges with intravenous (IV) and subcutaneous (SC) HMA therapies, including pain related to treatment administration and interference with daily activities; most patients also indicated a preference to switch to an oral therapy if one were available. Objectives: This study evaluated the perspectives of US patients with MDS receiving oral decitabine/cedazuridine (DEC-C), an alternative to IV/SC HMAs. Methods: An online survey was conducted among adult patients with MDS in the United States (10 November 2022 to 5 December 2022) who had filled a prescription for oral DEC-C between 2021 and 2022. Results: A total of 150 patients completed the survey; 61% were aged ⩾60 years and 63% were male. Of these, 123 (82%) were still receiving oral DEC-C, and 27 (18%) had stopped oral DEC-C treatment. Half (50%) of patients had received oral DEC-C for ⩾6 months. The majority reported that treatment was convenient (83%) and that they were satisfied with treatment (86%). Most patients also reported very little/no interference with regular daily activities (82%), social activities (78%), and productivity (78%). When queried about negative impacts on quality of life (QOL), treatment side effects were the most commonly reported (30% of respondents). Among patients who had previously received IV/SC HMAs (n = 91), most agreed that oral DEC-C interfered less with daily life (91%) and had experienced improvement in QOL (85%) compared with previous treatment; 91% reported that oral DEC-C reduced the number of times they needed to travel to a healthcare facility. Conclusion: Survey results suggest very little/no impact on regular daily activities and improved QOL with oral DEC-C relative to IV/SC HMAs, highlighting the potential for oral DEC-C to reduce the treatment burden associated with parenteral HMA therapy.

Kidney involvement in myelodysplastic syndromes.

Introduction: The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. Methods: We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9 g/g, and median serum creatinine was 3.2 mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. Conclusion: The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.

MicroRNA dysregulation in myelodysplastic syndromes: implications for diagnosis, prognosis, and therapeutic response.

Myelodysplastic syndromes (MDS) are a group of malignant clonal hematological disorders with heterogeneous clinical course and risk of transformation to acute myeloid leukemia. Genetic and epigenetic dysregulation, including alterations in microRNA (miRNA) expression, plays a pivotal role in MDS pathogenesis influencing disease development and progression. MiRNAs, known for their regulatory roles in gene expression, have emerged as promising biomarkers in various malignant diseases. This review aims to explore the diagnostic and prognostic roles of miRNAs in MDS. We discuss research efforts aimed at understanding the clinical utility of miRNAs in MDS management. MiRNA dysregulation is linked to specific chromosomal abnormalities in MDS, providing insights into the molecular landscape of the disease. Circulating miRNAs in plasma offer a less invasive avenue for diagnostic and prognostic assessment, with distinct miRNA profiles identified in MDS patients. Additionally, we discuss investigations concerning the role of miRNAs as markers for treatment response to hypomethylating and immunomodulating agents, which could lead to improved treatment decision-making and monitoring. Despite significant progress, further research in larger patient cohorts is needed to fully elucidate the role of miRNAs in MDS pathogenesis and refine personalized approaches to patient care.