INDUSTRY

Workshop organised by Beckman Coulter

Wednesday 20 August,17:45 – 18:30, Hall L1+L2

Speakers:          

Prof. Dr. Shahram Kordasti, King’s College London, UK

Dr. Michael Kapinsky, Beckman Coulter Life Sciences, Germany

Description

While the IPSS-M represents a significant step forward in integrating molecular data into MDS risk stratification, it lacks immunological granularity—limiting its utility in guiding inflammation-targeted and immunomodulatory therapies. Recent work from our group and others highlights that immune dysregulation in MDS is neither uniform nor secondary, but often integral to disease biology.

Inflammation in MDS is shaped by the mutational background of the malignant clone. For instance, SF3B1-mutant MDS exhibits distinct immunophenotypic features—such as HLA-DRlow monocytes and reduced mature NK cells—not seen in SF3B1 wild-type cases. These alterations are functionally relevant: canakinumab’s limited efficacy in SF3B1-mutant MDS appears to stem from impaired monocyte-CD8+ T cell interactions, highlighting the context-specific impact of anti-inflammatory strategies.

Similarly, P53 dysfunction is associated with heightened interferon signalling and suppression of antigen presentation pathways in classical and non-classical monocytes. Single-cell multi-omic studies reveal a profoundly altered immune landscape in these patients, including an accumulation of dysfunctional regulatory T cells (Tregs).

These findings reinforce the need for mutationally stratified immune intervention, rather than broad inflammation-directed approaches.

Parallel to this is the growing recognition of immune-mediated bone marrow failure (iBMF) as an under-recognised and poorly defined subset within the MDS spectrum. Often hypercellular and lower-risk, iBMF cases blur the line between MDS and aplastic anaemia (AA), with T cell-driven suppression of haematopoiesis and sensitivity to immunosuppressive therapy. Yet, current classifications do not adequately distinguish these patients, nor predict who will benefit from immunosuppressive treatment. Incorporating immune signatures—such as Treg frequency, monocyte phenotype, and inflammatory transcriptomic profiles—may help identify and personalise care for this subgroup.

The i4MDS initiative proposes a conceptual and practical framework to integrate immune profiles into prognostic models like IPSS-M. Using longitudinal data from deeply phenotyped cohorts, including patients stratified by WHO 2022 and IPSS-M, we are developing an immune classification overlay that refines current risk groups and identifies actionable immune subtypes. Early analyses suggest that adding immune context enhances prediction of AML evolution and therapeutic response, particularly for agents targeting inflammation or immune checkpoints. The ultimate goal is to move beyond molecular risk stratification alone and towards a multi-dimensional model that incorporates the genomic and immunological landscape as a determinant of both prognosis and response to treatment.