Activation of Distinct Inflammatory Pathways in LR-MDS Is Determined By Genetics

Schneider, Moritz; Rolfs, Clara; Trumpp, Matthias; Winter, Susann; Fischer, Luise; Richter, Mandy; Menger, Victoria; Nenoff, Kolja; Grieb, Nora; Kubasch, Anne Sophie; Metzeler, Klaus H.; Sockel, Katja; Thiede, Christian; Hofbauer, Lorenz C.; Roth, Andreas; Bruederle, Andreas; Woo, Janghee; Cross, Michael; Platzbecker, Uwe

doi:10.1182/blood-2022-163246

Cited by 5 publications

(5 citation statements)

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“…S2). These results are consistent with the reported lower proportion of lymphocytes in BM [8], mild myeloid dysplasia [9], and our previous finding of significantly lower IL1B mRNA in BM monocytes from SF3B1 mut LR-MDS [10]. As IL-1β protein levels in paired BM plasma samples were often below the detection limit, we could not determine whether lower mRNA levels correspond to lower cytokine levels.…”

supporting

confidence: 87%

“…9 Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy. 10 Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany. 11 National Center for Tumor Diseases (NCT); German Cancer Research Center (DKFZ); Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.…”

mentioning

confidence: 99%

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Mutations in the splicing factor SF3B1 are linked to frequent emergence of HLA-DRlow/neg monocytes in lower-risk myelodysplastic neoplasms

Winter,

Schneider,

Oelschlaegel

et al. 2024

Leukemia

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confidence: 87%

mentioning

confidence: 99%

Mutations in the splicing factor SF3B1 are linked to frequent emergence of HLA-DRlow/neg monocytes in lower-risk myelodysplastic neoplasms

Winter,

Schneider,

Oelschlaegel

et al. 2024

Leukemia

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“…Canakinumab, an interleukin 1 beta (IL-1β) inhibitor, has been explored in patients with LR-MDS. An ex vivo study revealed that the IL-1β-neutralizing antibody canakinumab markedly enhanced the colony-forming activity of HSPCs when cocultured with BM monocytes from SF3B1-mutated LR-MDS [255]. Results from phase II clinical trials confirmed that canakinumab is safe and effectively targets IL-1β signaling, and yielded durable response in LR-MDS patients with single somatic driver mutation in TET2 or DNMT3A [256,257].…”

Section: Treatment Options For Lr-mds Patientsmentioning

confidence: 95%

Role of reactive oxygen species in myelodysplastic syndromes

Jing,

Zhou,

Zhang

et al. 2024

Cell Mol Biol Lett

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Reactive oxygen species (ROS) serve as typical metabolic byproducts of aerobic life and play a pivotal role in redox reactions and signal transduction pathways. Contingent upon their concentration, ROS production not only initiates or stimulates tumorigenesis but also causes oxidative stress (OS) and triggers cellular apoptosis. Mounting literature supports the view that ROS are closely interwoven with the pathogenesis of a cluster of diseases, particularly those involving cell proliferation and differentiation, such as myelodysplastic syndromes (MDS) and chronic/acute myeloid leukemia (CML/AML). OS caused by excessive ROS at physiological levels is likely to affect the functions of hematopoietic stem cells, such as cell growth and self-renewal, which may contribute to defective hematopoiesis. We review herein the eminent role of ROS in the hematological niche and their profound influence on the progress of MDS. We also highlight that targeting ROS is a practical and reliable tactic for MDS therapy. Graphical Abstract

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“…Low‐risk (LR) MDS are characterized by a “proinflammatory state” with a higher prevalence of effector cells (e.g., Th17 and CTL) 8,23 whereas high‐risk (HR) MDS are dominated by an “immunosuppressive state” with increased regulatory T cells (Tregs) 7 . We highlight the complex modifications in cell repertoire that occur during MDS progression (Figure 2 and Table 1).…”

Section: Immune Cell Dysregulations In Myelodysplastic Neoplasmsmentioning

confidence: 95%

Immune‐monitoring of myelodysplastic neoplasms: Recommendations from the i4MDS consortium

Tentori,

Zhao,

Tinterri

et al. 2024

HemaSphere

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Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing “immune classes” among MDS patients is the absence of validated accepted immune panels suitable for routine application in clinical laboratories. In response, we formed International Integrative Innovative Immunology for MDS (i4MDS), a consortium of multidisciplinary experts, and created the following recommendations for standardized methodologies to monitor immune responses in MDS. A central goal of i4MDS is the development of an immune score that could be incorporated into current clinical risk stratification models. This position paper first consolidates current knowledge on MDS immunology. Subsequently, in collaboration with clinical and laboratory specialists, we introduce flow cytometry panels and cytokine assays, meticulously devised for clinical laboratories, aiming to monitor the immune status of MDS patients, evaluating both immune fitness and identifying potential immune “risk factors.” By amalgamating this immunological characterization data and molecular data, we aim to enhance patient stratification, identify predictive markers for treatment responsiveness, and accelerate the development of systems immunology tools and innovative immunotherapies.

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Activation of Distinct Inflammatory Pathways in LR-MDS Is Determined By Genetics

Cited by 5 publications

References 0 publications

Mutations in the splicing factor SF3B1 are linked to frequent emergence of HLA-DRlow/neg monocytes in lower-risk myelodysplastic neoplasms

Mutations in the splicing factor SF3B1 are linked to frequent emergence of HLA-DRlow/neg monocytes in lower-risk myelodysplastic neoplasms

Role of reactive oxygen species in myelodysplastic syndromes

Immune‐monitoring of myelodysplastic neoplasms: Recommendations from the i4MDS consortium

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