AML progression

• Preclinical data indicate ROS damage lipids, proteins and nucleic acids which could lead to mutations resulting in malignant progression¹. info
• In a pre-clinical model of AML development, mice received ionizing radiation followed by iron dextran. LFS was 100% in controls, but several mice in the IOL group developed AML².
• In MDS, IOL promotes genomic instability in bone marrow cells. Three groups were examined, those with normal SF level (n=29), SF levels >normal up to 1005ng/mL (n=23) & SF >1005ng/mL (n=8) using CGA. Size of genomic aberrations in patients with elevated SF was larger (87.5 vs 0 mbp, p=0.005) & age-adjusted neutrophil telomere length was shorter (p=0.003)³.
• In the US Medicare study, TD patients had a higher rate of progression to AML (24.6% vs 9.6%, p<0.001). AML-free survival was also inferior in TD patients from Pavia (HR 2.02, p<0.001)^4,5.
• Preclinical data document inhibitory activity of ICT on proliferation of leukemia cells & cell lines^6-9.
• In clinical studies in MDS; in a matched pair analysis from the Dusseldorf MDS Registry, there was no difference between groups in AML progression. In a second analysis, a delay in AML progression was seen in patients receiving ICT (p<0.0001)^10,11.