Plasmatic L-AScorbic Acid in MYelodyplastic Syndroms and Controls

Kinetics of the Plasmatic Concentration of L-Ascorbic Acid in Patient With Myelodysplastic Syndromes and Control Subjects

Myelodysplastic syndromes (MDS) is a group of heterogeneous diseases characterised by the clonal evolution of dysplastic hematopoietic stem cells. This evolution is associated with accumulation of cytogenetic mutations which leads to acute myeloid leukaemia (AML). Evolution of MDS is also associated with increase of reactive oxygen species (ROS). The increase of ROS is associated with accumulation of cytogenetic mutations. Ascorbic acid (AA) is an actor of the regulation of the oxidative metabolism in the human body.

Studies showed that supplementation with AA can change the proliferation status of MDS cells. Adjuvant treatment with AA is associated with a beneficial effect on the evolution of MDS and AML. The present study aim at describing the variations of plasmatic ascorbic acid concentrations between healthy volunteers and patients with myelodysplastic syndromes advanced in their treatment or recently diagnosed during a follow-up of 12 months.

Myelodysplastic syndromes (MDS) is a group of heterogeneous life threatening diseases characterised by the clonal evolution of dysplastic myeloid hematopoietic stem cells. This evolution is initially associated with an excess of apoptosis followed by an excess of proliferation then, after accumulation of cytogenetic mutations, a transformation in acute myeloid leukaemia (AML) can appear. Evolution of MDS is also associated with increase of reactive oxygen species (ROS) . In MDS mice, perturbations of the metabolism of ROS is associated with increases in the number of cytogenetic mutations.

Ascorbic acid (AA) is an actor of the regulation of the oxidative metabolism in the human body. In vitro studies showed that supplementation with AA can change the proliferation status of MDS cells . Guinea pigs with a phenotype with excess of ROS supplemented with AA have less somatic mutations and less MDS. Adjuvant treatment with AA is associated with a beneficial effect on the evolution of MDS and AML.

To our knowledge no study have demonstrated the variations of the parameters of the oxidative metabolism during the evolution of MDS. The present study aim at describing the variations of plasmatic ascorbic acid concentrations between healthy volunteers and patients diagnosed with MDS in treatment or recently diagnosed during a follow-up of 12 months. During the follow-up a collection of plasma from volunteers and patients will be created for later analysis.

1. Patients MDS "at diagnosis" group selection criteria

   Inclusion Criteria:

   • Diagnosis of myelodysplastic syndrome according to the 2008 WHO classification
   • Patient diagnosed for less than 4 months before inclusion
   • Patient untreated by other means than blood transfusions
   • Age ≥ 60 years
   • Patient affiliated to social security scheme
   • Informed consent signed by the patient

   Exclusion Criteria:

   • Previous allogenic stem cell transplantation
   • Patient with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
   • Active inflammatory disease
   • Patient under legal protection measure
   • Patient unwilling or who cannot submit to prospective biological follow-up

2. Patients MDS "in treatment" group selection criteria:

   Inclusion Criteria:

   • Diagnosis of myelodysplastic syndrome according to the 2008 WHO classification
   • Patient not included in patients MDS "at diagnosis" group
   • Patient diagnosed for more than 12 months
   • Treated with hypomethylating agents and/or erythropoiesis-stimulating agents and/or blood transfusions.
   • Age ≥ 60 years
   • Patient affiliated to social security scheme
   • Informed consent signed by the patient

   Exclusion Criteria:

   • Previous allogenic stem cell transplantation
   • Patient with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
   • Active inflammatory disease
   • Patient under legal protection measure
   • Patient unwilling or who cannot submit to prospective biological follow-up

3. Healthy volunteers group selection criteria:

Inclusion Criteria:

• Age ≥ 60 years
• Patient affiliated to social security scheme
• Informed consent signed by the patient

Exclusion Criteria:

• History of another primary malignancy that is currently clinically significant or currently requires active intervention
• History of active inflammatory diseases
• Volunteer under legal protection measure
• Volunteer unwilling or who cannot submit to prospective biological follow-up