[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.

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.

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.

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.

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.

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.

Increased ferroptosis of erythrocytes is associated with myelodysplastic syndromes.

Anemia is the most common symptom in patients with myelodysplastic syndromes (MDS). Programmed cell death of erythrocytes is one of the contributing factors to anemia. Ferroptosis is a newly identified form of iron-dependent cell death. The aim of this study is to investigate whether anemia in MDS patients is associated with ferroptosis of nucleated erythrocytes(NEs).We detected lipid peroxidation levels, Fe2+ contents, cell death rates, glutathione (GSH) and malondialdehyde (MDA) levels in bone marrow CD235a+ NEs of MDS patients. Expression levels of ferroptosis-related molecules (ACSL4, GPX4, and SLC7A11) were evaluated through qRT-PCR and Western Blotting. Correlation between these markers and clinical parameters were analyzed. To further substantiate that the mode of cell death with CD235a+ NEs of MDS patients was attributed to the ferroptosis pathway, we applied Fer-1 to inhibit ferroptosis. Cell viability was assessed using CCK8, and changes in ferroptosis-related indicators were simultaneously evaluated. We discover that the ferroptosis level of bone marrow NEs in MDS patients was increased, which is related to anemia and iron overload. Ferroptosis might be one of the causes of anemia in MDS patients.

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.

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].

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.

Deubiquitinases at the interplay between hematopoietic stem cell aging and myelodysplastic transformation.

Hematopoietic stem cells (HSC) maintain blood production throughout life. Nevertheless, HSC functionality deteriorates upon physiological aging leading to the increased prevalence of haematological diseases and hematopoietic malignancies in the elderly. Deubiquitinating enzymes (DUBs) by reverting protein ubiquitination ensure proper proteostasis, a key process in HSC maintenance and fitness.

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.

Current challenges in conditioning regimens for MDS transplantation.

Myelodysplastic syndrome (MDS) is a very heterogeneous clonal disorder. Patients with "higher-risk" MDS, defined by specific recurrent genetic abnormalities, have a poor prognosis because of a high risk of progression to secondary acute myeloid leukemia with low chemosensitivity. Allogeneic hematopoietic stem cell transplantation remains the only treatment that offers durable disease control because the donor immune system allows graft-versus-MDS effects. In terms of preparation steps before transplantation, targeting the malignant clone by increasing the conditioning regimen intensity is still a matter of intense debate. MDS is mainly diagnosed in older patients, and high toxicity related to common myeloablative conditioning regimens has been reported. Efforts to include new drugs in the conditioning regimen to achieve the best malignant clone control without increasing toxicity have been made over the past 20 years. We summarized these retrospective and prospective studies and evaluated the limitations of the available evidence to delineate the ideal conditioning regimen.

[Clinical Characteristics and Prognosis of Myelodysplastic Syndromes Patients with RUNX1 Gene Mutation].

OBJECTIVE: To investigate the clinical characteristics and survival analysis of myelodysplastic syndromes (MDS) with RUNX1 gene mutation. METHODS: Clinical data of 177 newly diagnosed MDS patients admitted to the Department of Hematology, the Second Affiliated Hospital of Air Force Military Medical University from October 1, 2015 to October 31, 2022 were retrospectively analyzed. Gene mutation detection was performed by second-generation sequencing technology, and clinical characteristics and prognosis of patients with RUNX1 gene mutation were analyzed. RESULTS: A total of 30 cases (16.95%) of RUNX1 gene mutations were detected, including 15 missense mutations (50.0%), 9 frameshift deletion mutations (30.0%), 4 splice site mutations (13.3%), 1 insertion mutation (3.3%), and 1 nonsense mutation (3.3%). Patients with RUNX1 mutations had a median age of 68.5 years at diagnosis (range: 62.25-78.50 years old). There were no significantly differences between RUNX1 mutations and wild type patients in age distribution, gender, peripheral blood white blood cell count, hemoglobin level, bone marrow and peripheral blood blasts ratio, IPSS-R cytogenetics, IPSS-R stage, etc. (P >0.05). However, there were statistically significant differences in platelet count and whether complicated karyotype. Compared with patients without RUNX1 gene mutation, patients with RUNX1 gene mutation had lower platelet count (P =0.018), and were less likely to have complicatedkaryotype at initial diagnosis (P =0.01). Cox proportional hazards model analysis showed that when other covariates remained unchanged, the higher the platelet count, the better the survival of patients (HR=0.995, 95%CI : 0.990-0.999, P =0.036); In the IPSS-M prognostic stratification, keeping other covariates unchanged, the risk of progression or death of myelodysplastic syndrome was significantly lower in the medium to high-risk and low-risk groups compared with the high-risk group (HR=0.149, 95%CI : 0.031-0.721, P =0.018; HR=0.026, 95%CI : 0.003-0.234, P =0.001). Survival analysis showed that MDS patients with RUNX1 gene mutation had worse overall survival time (P < 0.001). Patients with RUNX1 mutation had worse OS than non-mutation patients in the early WHO group. RUNX1 mutation and IPSS-M risk stratification mean OS and mean LFS were worse in low-risk patients than in non-mutated patients. CONCLUSION: RUNX1 gene mutation is an adverse prognostic factor in MDS patients, especially in the IPSS-M prognosis stratification group of low-risk, medium-low risk, medium-high risk and WHO classification of early patients.

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.

Next generation sequencing reveals the mutation landscape of Chinese MDS patients and the association between mutations and AML transformations.

BACKGROUND/OBJECTIVE: Approximately 30% of patients with MDS eventually develop to acute myeloid leukemia (AML). Our study aimed to investigate the mutation landscape of Chinese MDS patients and identify the mutated genes which are closely implicated in the transformation of MDS to AML. METHODS: In total, 412 sequencing data collected from 313 patients were used for analysis. Mutation frequencies between different groups were compared by Fisher's exact. A predictive model for risk of transformation/death of newly diagnosed patients was constructed by logistic regression. RESULTS: The most frequently mutated genes in newly diagnosed patients were TP53, TET2, RUNX1, PIGA, and BCOR and mutations of RUNX1, TP53, BCORL1, TET2, and BCOR genes were more common in the treated MDS patients. Besides, we found that the mutation frequencies of IDH2, TET2, and EZH2 were significantly higher in MDS patients aged over 60 years. Moreover, two mutation sites, KRASG12A and TP53H140N were detected only at transformation in one patient, while not detected at diagnosis. In addition, the mutation frequencies of EZH2 V704F and TET2 I1873N were stable from diagnosis to transformation in two patients. Finally, we constructed a predictive model for risk of transformation/death of newly diagnosed patients combing detected data of 10 genes and the number of to leukocyte, with a sensitivity of 63.3% and a specificity of 84.6% in distinguishing individuals with and without risk of transformation/death. CONCLUSION: In summary, our study found several mutations associated with the transformation from MDS to AML, and constructed a predictive model for risk of transformation/death of MDS patients.

[Thiotert Induces Myelodysplastic Syndromes Cells Apoptosis by Activating Oxidative Stress].

OBJECTIVE: To explore whether thiotert treatment can inhibit proliferation and induce apoptosis in myelodysplastic syndromes (MDS) cells. METHODS: CCK-8 assay was used for determining the cytotoxicity of thiotert to MDS cell line SKM-1 and the reversal effect of GSH, NAC, and Z-VAD-FMK on thiotert-induced inhibition of cell viability. EdU assay was deployed to detect the cell proliferation ability. Intracellular reactive oxygen species (ROS) was measured by flow cytometry after DCFH-DA staining. The expression of DNA damage- and apoptosis-related proteins was detected by Western blot. RESULTS: Thiotert treatment significantly suppressed the cell viability and proliferation ability in SKM-1 cells. A large amount of ROS generation and markedly elevated C-PARP, C-Caspase 3, and γ-H2AX were observed after thiotert administration, while BCL-2 was significantly decreased. In addition, GSH, NAC, and Z-VAD-FMK were able to mitigate the cytotoxicity of thiotert on SKM-1 cells. CONCLUSION: Thiotert can promote MDS cell apoptosis by mediating ROS production and pro-apoptotic proteins expression.

Micro-transplantation in an elderly patient with very high risk MDS:A case report and literature review.

Introduction: The prognosis of patients with myelodysplastic syndromes (MDS) (very high risk) is poor.HLA-mismatched allogeneic T-cell infusion which is called micro-transplantation can not only shorten the time of bone marrow suppression, but also improve the treatment response of patients. Case presentation: A 74-year-old woman presented with fatigue and showed pancytopenia on routine blood count. She was diagnosed with MDS (very high risk) after bone marrow examination,then she received 4 cycles of micro-transplantation. The progression-free survival was 22 months and overall survival was 33 months. Discussion: The patient showed good tolerance to micro-transplantation with manageable toxicities and short myelosuppression time.

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.