Myeloid Disease Research Articles

Multi-parametric MRI for the evaluation of cranial nerves dysfunction in hematological malignancies

BackgroundIn hematological malignancies which include a heterogeneous group of neoplastic lymphoid or myeloid disease, cranial nerve dysfunction (CND) is not uncommon and can occur secondary to a wide range of potential etiologies. CND may be due to infiltration, infection, and therapeutic complications with broad spectrum of clinical manifestation.Aim of workMagnetic resonance imaging (MRI) is essential for evaluating cranial nerves. Our aim was to investigate multi-parametric MRI approach for the evaluation of cranial nerve dysfunction, to differentiate between possible etiologies and illustrate the potential diagnostic challenges in the context of hematological malignancies. We aimed to differentiate between cranial nerve infiltration and non-infiltrative causes, thereby avoiding unnecessary radiation or chemotherapy.MethodsOur retrospective study included 30 patients (13 females and 17 males) presented with CND into hematology–oncology clinic from February 2019 to March 2022. The patients have been categorized into three groups: infiltration, infection, and treatment-induced cranial neuropathy, according to the pathology results, clinic–laboratory findings, response to treatment or by exclusion. The MR imaging criteria included cranial nerve involvement, solitary versus multiple, unilateral versus bilateral, size of the nerve, signal intensity on T1, T2, FLAIR, and diffusion-weighted imaging, and pattern of enhancement. The imaging features correlated to each category.ResultsThe cohort included 15 patients with leukemia, 14 patients with lymphoma, and only one patient with juvenile xanthogranuloma. Bilateral cranial nerves involvement was observed in 46.7% (n = 14) with the optic nerve being the most frequently affected. The infiltration group was the most prevalent and represented 66.7% (n = 20). Eleven patients (55%) presented with isolated cranial nerve involvement while the remaining 45% had perineural spread along the course of the cranial nerve from a remote focal mass. Optic nerve was the most common involved cranial nerve 63% (n = 19), followed by trigeminal nerve 40% (n = 12). Diffusion restriction along with heterogeneous pattern of enhancement was evident in all cases of neoplastic infiltration.ConclusionImaging criteria from multiple MR sequences are helpful in the evaluation of CND in patients with hematological malignancies which would promptly guide patient management and minimize unnecessary and risky biopsies. Diffusion-weighted imaging (DWI) appeared to be a good imaging marker, as diffusion restriction was exclusively appreciated in the malignant infiltrative group of CND.

Prospective, Randomized, Comparative Study of Myeloablative Fludarabine/Busulfan and Fludarabine/Busulfan/Total Body Irradiation Conditioning in Myeloid Diseases.

Background/Objectives: Allogeneic hematopoietic stem cell transplantation (alloSCT) is a curative treatment for myeloid diseases, yet relapse remains the major cause of post-transplant mortality. To reduce the risk of recurrence, we evaluated the addition of 400 cGy total body irradiation (TBI) to conditioning with fludarabine-busulfan (Flu/Bu4). Methods: In this prospective study, 46 patients with myeloid diseases were randomized to Flu/Bu4 or Flu/Bu4/TBI conditioning group. The Flu/Bu4 conditioning regimen consisted of fludarabine 40 mg/m2 on days -6 to -3 followed by busulfan 130 mg/m2 on days -6 to -3. Flu/Bu4/TBI conditioning regimen added 400 cGy TBI on day -1 to the FluBu4 regimen. Results: Among 34 acute myeloid leukemia (AML) patients, relapse was numerically lower in those who received Flu/Bu4/TBI (25%) versus Flu/Bu4 (44.4%) at three years (HR = 0.58, 95% CI 0.19 to 1.81, p = 0.35). Flu/Bu4/TBI appeared to increase the risk of non-relapse mortality (NRM) vs. Flu/Bu4 in AML patients at three years (25.0% versus 11.1%; HR = 2.11, 95% CI 0.51 to 8.83, p = 0.65). Overall survival (OS) was similar in AML patients undergoing conditioning with Flu/Bu4 (72.2%) versus Flu/Bu4/TBI (62.5%) at one year (p = 0.4). Conclusions: In conclusion, the addition of 400 cGy TBI to Flu/Bu4 reduced the risk of relapse but did not improve OS as a consequence of higher regimen-related mortality. Clinicaltrials.gov identifier: NCT01366612.

Allogeneic Haematopoietic Stem Cell Transplantation Using Reduced-Intensity Fludarabine, Busulfan and Anti-T-Lymphocyte Globulin With Strategic Donor Lymphocyte Infusion in Older Patients With Myeloid Malignancy.

Fludarabine, busulfan, and anti-T-lymphocyte globulin (FLUBU3+ATLG) reduced-intensity conditioning is an established preparative regimen for allogeneic haematopoietic stem cell transplantation in older patients with myeloid malignancy. We examined its modern-day performance in 175 sequentially treated patients on our national programme. Overall survival was 72.4% at 2 years (95% CI 64.6%-78.6%) with a cumulative incidence of non-relapse mortality of 11%. The cumulative 2-year relapse incidence was 27% (95% CI 22.8%-37.6%) and was partially ameliorated by chronic graft-versus-host disease (HR 0.35, 95% CI 0.12-0.98, p = 0.02). Mixed donor chimerism was observed in 51.5% beyond day 90, but relapse was significantly reduced in these patients by adopting a pre-emptive donor lymphocyte infusion (DLI) strategy (HR 0.22, 95% CI 0.07-0.69, p = 0.005). The use of DLI as part of post-relapse salvage was also effective, with an improved median survival duration of 6 months in recipients (HR 0.43, 95% CI 0.18-0.98, p = 0.01). Outcomes in patients > 65 years and a limited cohort > 70 years are encouraging and compare favourably to published survival results using alternate reduced-intensity regimens. FLUBU3+ATLG, supported by modern supportive care and a pre-emptive DLI strategy, is well tolerated by older patients across a spectrum of myeloid disease with modest toxicity and favourable long-term outcomes.

An integrated DNA interactome and transcriptome profiling reveals a PU.1/enhancer RNA-mediated Feed-forward Regulatory Loop Regulating monocyte/macrophage development and innate immune functions.

High expression of the myeloid master ETS transcription factor PU.1 drives the development of monocyte/macrophage (Mono/MΦ), a crucial cellular component of the innate immune system. Disruptions in normal expression patterns of PU.1 are linked to a variety myeloid malignancy and immune diseases. It is evidenced that PU.1 binds to and modulates enhancers of several myeloid genes. While noncoding RNAs transcribed from noncoding genes at the enhancers are increasingly reported to be involved in enhancer regulation, the crosstalk between PU.1 and noncoding RNAs in enhancer-mediated myeloid gene regulation in Mono/MΦ differentiation and immune response has not been systematically investigated. In this study, we interrogated the PU.1-mediated transcriptome and cistrome with our comprehensive collection of putative and verified enhancers. Among a repertoire of noncoding genes present at PU.1-bound enhancers, we discovered that PU.1 acts as a potent transcription factor inducer of the noncoding RNA LOUP , which we previously identified as an RNA inducer of PU.1. The genomic region within the LOUP locus occupied by PU.1 is characterized by the epigenetic features of a myeloid-specific super-enhancer. Targeted disruption of the PU.1-binding motifs resulted in the downregulation of LOUP promoter activity. Depletion of LOUP reduced the expression of Mono/MΦ cell markers as well as the transcriptional program associated with Mono/MΦ differentiation Mono/MΦ innate defense mechanisms, including phagocytosis, antimicrobial activity, and chemoattractant cytokine production. LOUP induces Mono/MΦ phagocytic activities. Collectively, our findings indicate that PU.1 and enhancer RNA LOUP are biomolecular components of an unidentified feed-forward loop that promotes their mutual expression, contributing to Mono/MΦ differentiation and innate immune functions. The identification of the PU.1/ LOUP regulatory circuit provides valuable insights into the mechanisms underlying cell-type and gene-specific enhancer activity and Mono/MΦ biology, as well as significant implications for advancing our understanding of immune diseases and myeloid malignancies.

Flow cytometry evaluation of acute myeloid leukemia minimal residual disease based on an understanding of the normal maturation patterns in the blast compartments.

Detection of minimal/measurable disease (MRD) in acute myeloid leukemia (AML) is critical for both clinical decision-making and prognostication, yet remains a challenge. Flow cytometry is a well-established method for MRD detection. Flow cytometric (FC) evaluation of MRD must consider a complex maturational pattern of normal hematopoietic development to separate normal from abnormal progenitors. Here, we offer an example of an interpretive approach based on a thorough understanding of stage- and lineage-specific hematopoietic maturation. We provide a comprehensive overview of blast maturation from early precursors (hematopoietic stem cells) to committed late-stage unilineage progenitors and commonly observed stage-specific abnormalities based on cases we have encountered in practice. We emphasize the importance of stage-specific comparisons for accurate MRD detection by flow cytometry. The AML blasts almost invariably show abnormal phenotypes, and the phenotypes may evolve upon therapy. The detected phenotypes are necessarily confined to the target antigens included in the panel. It is therefore critical to evaluate a range of antigens to establish a specific stage/state of lineage commitment and detect potential common abnormalities. Moreover, enough cells must be acquired to allow for the detection of MRD at desired levels. Significant technical and analytical validation is critical. Flow cytometry offers a powerful single-cell-based platform for MRD detection in AML, and the results have been proven critical for disease management. Leukemia-associated phenotype-informed difference from the normal approach presented in this review presents an analytical framework for sensitive and accurate MRD detection.

Health-Related Values Discussions with Patients Undergoing Allogeneic and Autologous Stem Cell Transplant: Feasibility and Acceptability of an Early Primary Palliative Care Intervention.

Health-Related Values Discussions with Patients Undergoing Allogeneic and Autologous Stem Cell Transplant: Feasibility and Acceptability of an Early Primary Palliative Care Intervention.

PATHOGENIC PRE-LEUKEMIC MUTATIONS: RARE IN CLONAL HEMATOPOIESIS BUT ENRICHED IN MYELOID DISEASES

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) refers to the expansion of peripheral blood cells derived from hematopoietic stem cells (HSCs) with at least one somatic driver mutation in healthy elderly individuals. CHIP is strongly linked to aging and confers an increased risk for blood cancers, non-hematological diseases (e.g. cardiovascular disease), and all-cause mortality. In blood cancers, CHIP mutations are associated with initiation of acute myeloid leukemia (AML) and other myeloid diseases and thus considered as pre-leukemic mutations. However, some pathogenic pre-leukemic mutations are rarely found in CHIP patients. We will talk about two of such mutations. The first one is the hot spot G646WfsX12 mutation in the epigenetic regulator ASXL1. This mutation occurs in ~18% of patients with myeloid diseases but almost never found in CHIP patients. Using a knockin animal model (Atm/+), we show that Atm/+ HSCs were only expanded in aged mice but not in young mice. We are investigating if the mutant HSC expansion is caused by reduced immunosurveillance of aged immune cells and/or aged pro-inflammatory stromal cells. The second one is oncogenic NRASG12D mutation, which serves as an initiation or progression mutation in chronic myelomonocytic leukemia. It is shown that one copy of NRASG12D mutation confers bi-modal regulation of HSCs in which it enhances self-renewal in one subset of HSCs but promotes proliferation and exhaustion in another subset of HSCs. We hypothesize that ASXL1G646WfsX12 and NRASG12D mutations belong to the pathogenic pre-leukemic mutations, which easily incorporate additional mutations in leukemogenesis rather than remain stable in CHIP.

In Vivo Induction of Leukemia-Specific Adaptive and Innate Immune Cells by Treatment of AML-Diseased Rats and Therapy-Refractory AML Patients with Blast Modulating Response Modifiers.

There is a high medical need to develop new strategies for the treatment of patients with acute myeloid leukemia (AML) refractory to conventional therapy. In vitro, the combinations of the blast-modulatory response modifiers GM-CSF + Prostaglandin E1, (summarized as Kit M) have been shown to convert myeloid leukemic blasts into antigen-presenting dendritic cells of leukemic origin (DCleu) that were able to (re-)activate the innate and adaptive immune system, direct it specifically against leukemic blasts, and induce memory cells. This study aimed to investigate the immune modulatory capacity and antileukemic efficacy of Kit M in vivo. Brown Norway rats suffering from AML were treated with Kit M (twofold application). Blasts and immune cells were monitored in peripheral blood (PB) and spleen. Upon the observation of promising immune modulatory effects in the treated animals, two patients with AML refractory to multiple lines of therapy were offered treatment with Kit M on an individualized basis. Safety, as well as immunological and clinical effects, were monitored. Samples obtained from a third patient in similar clinical conditions not receiving Kit M were used as controls for immune monitoring tests. Animal experiments: Drugs were well tolerated by the treated animals. After 9 days of treatment, DCleu and memory-like T cells increased in the peripheral blood, whereas regulatory T cells, especially blasts, decreased in treated as compared to untreated control animals. Clinical courses: No severe side effects were observed. In patient 1482, PB blasts remained under the detection threshold during 27 days of treatment, thrombocytes were normalized, and (leukemia specific) immune effector cells of the adaptive and innate immune system increased up to 800-fold compared to the start of treatment. Patient 1601 responded with a 12% reduction in blasts in PB immediately after Kit M treatment. Several subtypes of (leukemia-specific) immune effector cells in PB increased up to four-fold during the 19 days of treatment. In contrast, immune-reactive cells decreased under mild chemotherapy in the PB of control patient 1511 with comparably refractory AML. Within the limitation of low numbers in both animal experiments and clinical applications, our data suggest that Kit M treatment of AML-diseased rats and patients is feasible and may induce leukemia-specific immune reactions and clinical improvement. A larger series and a prospective clinical trial will be required to confirm our observations. Beyond optimized doses and schedules of the applied compounds, the combination with other antileukemic strategies or the application of Kit M in less proliferative stages of the myeloid diseases need to be discussed. If effects are confirmed, the concept may add to the armamentarium of treatments for highly aggressive blood cancer.

Nontransplant treatment approaches for myeloid neoplasm with mutated TP53.

TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remain a challenging spectrum of clonal myeloid disease with poor prognosis. Recent studies have shown that in AML, MDS, and MDS/AML with biallelic TP53 loss, the TP53-mutated clone becomes dominant. These are highly aggressive diseases that are resistant to most chemotherapies. The latest 2022 International Consensus Classification categorizes these diseases under "myeloid disease with mutated TP53." All treatment approaches have not improved survival rates for this disease. Many newer therapies are on the horizon, including chimeric antigen receptor T/NK-cell therapies, mutated p53 reactivators, Fc fusion protein, and monoclonal antibodies targeting various myeloid antigens. This review summarizes the current approaches for myeloid disease with TP53 mutation and provides an overview of emerging nontransplant approaches.

Transplant options and outcomes for TP53 myeloid disease.

TP53-mutated myeloid disease is a constellation of abnormalities seen in both de novo and therapy-related acute myeloid leukemia and myelodysplastic syndrome. Historically, this group of disorders has had a poor prognosis. Newer treatment combinations allow patients to be treated with less toxicity. If response to induction therapy is achieved, fit and willing patients should be considered for allogeneic hematopoietic cell transplantation (HCT). The addition of allogeneic HCT to the treatment approach has modestly improved outcomes compared to chemotherapy alone, more so for those patients with disease control. Tailoring the conditioning regimen and maintenance therapy may improve outcomes in TP53 myeloid patients. In addition to chemotherapy, disease-modulating and immunological treatments continue to be studied to further improve outcomes.

Higher relapse and worse overall survival in recipients with CTLA-4 AA genotype of rs231775 following single-unit cord blood transplantation in adults

We retrospectively investigated the impact of CTLA-4 polymorphism on outcomes for adult patients who received single-unit cord blood transplantation (CBT) at our institution. CTLA-4 genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs231775. This study included 143 recipient–donor pairs. The multivariate analysis showed that recipient rs231775 AA was associated with worse overall survival (OS) (hazard ratio [HR], 2.92; p = 0.008) and a higher relapse rate (HR, 4.79; p = 0.002), but donor rs231775 was not. The rs231775 polymorphism in recipients and donors did not affect non-relapse mortality, hematopoietic recovery, or acute and chronic graft-versus-host disease. The beneficial effects of rs231775 GG+GA recipients on OS and relapse were notable in subgroups of patients with high-risk disease status and those with myeloid diseases. The polymorphism of CTLA-4 rs231775in recipients might be associated with the clinical outcomes of single-unit CBT.

Diagnosis of TP53-mutated myeloid disease by the ICC and WHO fifth edition classifications

Diagnosis of TP53-mutated myeloid disease by the ICC and WHO fifth edition classifications

Spatial Transcriptomic Profiling of Bone Marrow Vascular Niches Unveils an Endothelial Stress Signature in Myeloproliferative Neoplasms

Spatial Transcriptomic Profiling of Bone Marrow Vascular Niches Unveils an Endothelial Stress Signature in Myeloproliferative Neoplasms

Integrating bulk and single-cell transcriptomics to elucidate the role and potential mechanisms of autophagy in aging tissue.

Autophagy is frequently observed in tissues during the aging process, yet the tissues most strongly correlated with autophagy during aging and the underlying regulatory mechanisms remain inadequately understood. The purpose of this study is to identify the tissues with the highest correlation between autophagy and aging, and to explore the functions and mechanisms of autophagy in the aging tissue microenvironment. Integrated bulk RNA-seq from over 7000 normal tissue samples, single-cell sequencing data from blood samples of different ages, more than 2000 acute myeloid leukemia (AML) bulk RNA-seq, and multiple sets of AML single-cell data. The datasets were analysed using various bioinformatic approaches. Blood tissue exhibited the highest positive correlation between autophagy and aging among healthy tissues. Single-cell resolution analysis revealed that in aged blood, classical monocytes (C. monocytes) are most closely associated with elevated autophagy levels. Increased autophagy in these monocytes correlated with a higher proportion of C. monocytes, with hypoxia identified as a crucial contributing factor. In AML, a representative myeloid blood disease, enhanced autophagy was accompanied by an increased proportionof C. monocytes. High autophagy levels in monocytes are associated with pro-inflammatory gene upregulation and Reactive Oxygen Species (ROS) accumulation, contributing to tissue aging. This study revealed that autophagy is most strongly correlated with aging in blood tissue. Enhanced autophagy levels in C. monocytes demonstrate a positive correlation with increased secretion of pro-inflammatory factors and elevated production of ROS, which may contribute to a more rapid aging process. This discovery underscores the critical role of autophagy in blood aging and suggests potential therapeutic targets to mitigate aging-related health issues.

Therapeutic strategies targeting aberrant RNA splicing in myeloid malignancies.

In recent years, large-scale sequencing efforts have identified targetable driver mutations in haematopoietic stem cells. These efforts have led to the development and approval of nine novel agents for relapsed or refractory acute myelogenous leukaemia (R/R AML). However, despite an expansion in targeted therapies, achieving a durable remission in AML and high-risk myelodysplastic syndrome (HR-MDS) remains a significant challenge, and there is an urgent need for new effective treatments. Modulation of aberrant RNA splicing has emerged as a novel therapeutic approach in myeloid diseases. Aberrant splicing drives dysregulated gene expression that promotes tumourigenesis through increased proliferation and metastatic potential, immune evasion, decreased apoptosis, and chemotherapy resistance. Mutations in spliceosomal components have been identified in numerous cancer subtypes, with mutations in RNA binding proteins SF3B1, SRSF2, U2AF1, and ZRSR2 occurring frequently in AML and in up to 60% of patients with MDS, as well as in chronic myelomonocytic leukaemia and in 10% of patients with chronic lymphocytic leukaemia. In this review, we explore therapeutic strategies targeting aberrant splicing and the potential of these approaches to drive clinical responses.

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.

Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial

Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial

Breaking Boundaries: Immunotherapy for Myeloid Malignancies.

Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment options available to patients. Immunotherapy in myeloid malignancies, however, faces numerous challenges due to the dynamic nature of the disease, immune dysregulation, and the development of immune evasion mechanisms. This review outlines the progress made in the field of immunotherapy for myeloid malignancies, addresses its challenges, and provides insights into future directions in the field.

Tixagevimab/Cilgavimab for COVID-19 Pre-Exposure Prophylaxis in Hematologic Patients-A Tailored Approach Based on SARS-CoV-2 Vaccine Response.

Patients with hematologic malignancies still face a significant risk of severe coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-neutralizing monoclonal antibody combination tixagevimab/cilgavimab (TIX/CGB) could be administered to immunocompromised patients for pre-exposure prophylaxis (PrEP) before the emergence of TIX/CGB-resistant COVID-19 Omicron variants. TIX/CGB application could be carried out regardless of the host's immune response to previous active SARS-CoV-2 vaccinations or infections. Because the efficacy of COVID-19 PrEP remains unclear, especially in SARS-CoV-2-seropositive patients, German national guidelines recommended TIX/CGB PrEP only for SARS-CoV-2-seronegative patients in addition to an intensified active vaccination schedule. Having followed these guidelines, we now report the characteristics and outcomes of 54 recipients of TIX/CGB PrEP in SARS-CoV-2-seronegative patients with hematological disease from a German tertiary medical center and compare them to 125 seropositive patients who did not receive any PrEP. While the number of patients with B-cell lymphomas was significantly higher in the seronegative cohort (33 (61%) vs. 18 (14%) cases, p < 0.01), patients with myeloid diseases were significantly more frequent in the seropositive cohort (51 (41%) vs. 5 (9%) cases, p < 0.01). Strikingly, patients who had undergone allogeneic hematopoietic stem cell transplantation were significantly more likely (forty-nine (39%) vs. six (11%) cases, p < 0.01) to be SARS-CoV-2 seropositive. We observed that prophylactic application of TIX/CGB PrEP to a highly vulnerable group of SARS-CoV-2-seronegative patients resulted in a similar number of COVID-19 breakthrough infections compared to the untreated seropositive control group (16 (32%) vs. 39 (36%), p = 0.62) and comparable COVID-19-related outcomes like hospitalization and oxygen requirement throughout an extended follow-up period of 12 months. In conclusion, our results support the tailored approach of administering TIX/CGB PrEP only to SARS-CoV-2-seronegative patients during the COVID-19 pandemic and might provide a rationale for similar strategies during future outbreaks/diseases, especially in times of initial limited availability and/or financial constraints.

The immunoregulatory role of monocytes and thrombomodulin in myelodysplastic neoplasms.

Myelodysplastic neoplasms (MDS) are clonal disorders of the myeloid lineage leading to peripheral blood cytopenias. Dysregulation of innate immunity is hypothesized to be a potent driver of MDS. A recent study revealed increased thrombomodulin (TM) expression on classical monocytes in MDS, which was associated with prolonged survival. TM is a receptor with immunoregulatory capacities, however, its exact role in MDS development remains to be elucidated. In this review we focus on normal monocyte biology and report on the involvement of monocytes in myeloid disease entities with a special focus on MDS. Furthermore, we delve into the current knowledge on TM and its function in monocytes in health and disease and explore the role of TM-expressing monocytes as driver, supporter or epiphenomenon in the MDS bone marrow environment.