Secondary acute myeloid leukemia and de novo acute myeloid leukemia with myelodysplasia-related changes - close or complete strangers?

Aim: To compare the main features of patients with secondary acute myeloid leukemias (AMLs) after post-myelodysplastic syndrome (AML-post-MDS) or post-myeloproliferative neoplasms (AML-post-MPN) and myeloid blast crisis of chronic myeloid leukemia (CML-BC) vs. de novoAMLs with myelodysplastic characteristics (dn-AML-MDS). Materials and methods: Bone marrow/peripheral blood samples of 94 patients with secondary AMLs (30 with AML-post-MDS, 20 with AML-post-MPN, and 14 with CML-BC) and 30 with dn-AML-MDS were included. Demographic, morphological, phenotypic, cytogenetic, and survival data were analyzed. Results: Comparative analysis showed no differences in sex and age, except for the younger age in CML-BC (p=0.005). Leukocytosis was a prevalent feature of CML-BC vs. AML-post-MPN, AML-post-MDS and dn-AML-MDS (p<0.001). At leukemia onset, thrombocytopenia was characteristic of AML-post-MDS and dn-AML-MDS whereas normal PLT counts were found in AML-post-MPN and CML-BC (p=0.001). Dysplasia in ≥2 lineages was observed in almost all dn-AML-MDS (96.8%) and AML-post-MDS (100%) compared to AML-post-MPN (33.3%) and none of the CML-BC (p=0.001). Aberrant co-expression of 1-4 lymphoid-associated markers was detected in 67.5% of all patients, including CD7, CD19, CD56, and CD22. We found chromosome aberrations in 57.8% of patients, more frequently in dn-AML-post-MDS than in AML-post-MPN, CML-BC, and AML-post-MDS. While NPM1 mutations distribution was similar in the two MDS-related AML groups, FLT3-ITD was higher in AML-post-MDS (26.3%) than in dn-AML-MDS (4.5%) (p=0.049). Regarding EVI1, CML-BC (80%) and AML-post-MPN (37.5%) showed higher incidence of gene overexpression compared to AML-post-MDS (13.3%) and dn-AML-MDS (5.0%) (p=0.001). Median time to leukemia was significantly shorter in AML-post-MDS (4.80±1.04 months) than in AML-post-MPN (20.3±2.86 months) and CML-BC (34.7±16.3 months) (p=0.008), and median overall survival was poor in all groups. Conclusions: Similarities and differences between patients with secondary AMLs may represent different biology which translates into different clinical course and may require different therapeutic approach in future.