Interplay Between Immune and Metabolic Programs in Myelodysplastic Syndromes

Interplay Between Immune and Metabolic Programs in Myelodysplastic Syndromes: Involvement in Leukemia Transformation and Therapeutic Targeting

Myelodysplastic syndromes (MDS) are a pre-leukemic condition with an extremely poor prognosis despite current treatments that justify new therapeutic approaches. Various studies have described the potential involvement of both immune compartment and cellular metabolism in the pathophysiology of MDS. The aim of this study is to determine the specific immune and metabolic profiles of the different classes of MDS and to identify predictive markers of progression/survival/response to therapy.

Myelodysplastic syndromes (MDS) are a pre-leukemic condition with an extremely poor prognosis despite current treatments. It is the most frequent haematological disorder after the age of 65. Different approaches targeting the immune compartment have been developed but preliminary results seem to show variable response rates to these therapeutic highlighting the heterogeneity of MDS and the need to identify detailed immune profiles that are predictive of disease progression and can help in treatment choices. It therefore seems essential to complement the knowledge of immune profiles with an understanding of the metabolic profiles of MDS patients, as well as the links between these profiles and changes associated with progression and/or treatment resistance, in order to consider new therapeutic pathways.

Fresh samples from patients with MDS will be used to perform flow cytometry mapping of immune populations, T-cell and blast cell metabolism. Subsequently, a study of energy metabolism will be conducted using an extracellular flow analyzer and a sensitivity test for certain molecules targeting metabolic pathways. If possible, samples will be taken at different times during the course of treatment, according to the therapeutic protocols: diagnosis, progression/transformation, during azacitidine treatment.

Inclusion Criteria:

• Patients:

  • Patient over 18 years of age with a myelodysplastic syndrome (WHO 2016 classification) of low risk (LR=IPSS-R<4.5) or high risk (HR=IPSS-R>4.5);
  • Patient naïve to specific treatment of MDS;
  • Patient who expressed no opposition to participating in the study. ;
  • Patient affiliated with the social security system.

• Control:

  • over 18 years of age,
  • Sample from blood donation (regardless of age) Or Patient >60 years old, see at the geriatrics platform of the hospital la Grave (CHU of Toulouse),
  • having expressed his non opposition to participate in the study

Exclusion Criteria:

• Patients:

  • Myeloid disease other than MDS (including chronic myelomonocytic leukemia and MDS/SMP) ;
  • Ongoing treatments for MDS (excluding erythropoietin, granulocyte colony-stimulating factor and transfusions) ;
  • Medical conditions that may interfere with immune system testing: active cancer, active autoimmune disease, inflammatory conditions, immunosuppressive therapy. ; * Pregnant or breastfeeding women ; Patient's refusal ;
  • Person benefiting from a system of protection for adults (including guardianship, curators and safeguarding of justice)

• Control:

  • Medical conditions that may interfere with immune system testing: active cancer, active autoimmune disease, inflammatory conditions, immunosuppressive therapy. ; * Pregnant or breastfeeding women ;
  • Patient's refusal ;
  • Person benefiting from a system of protection for adults (including guardianship, curators and safeguarding of justice)