Secondary and therapy-related acute myeloid leukemias: Overlapping features, distinct trajectories

Therapy-related acute myeloid leukemia (tAML) and AML arising from previous hematologic disorders (secondary AML, sAML) share similar biological features, including karyotype abnormalities and gene specific mutations, patient-related risk factors. Older age and lower performance status also contribute to dimal prognosis, and dismal prognosis, both in terms of response rate and overall survival. However, these 2 entities significantly differ in leukemogenic trajectories. In this line, recent advances allowed for a better understanding of differential clonal progression processes in the broad landscape of sAMLs. Thus, in this manuscript, we reviewed clinical and biological characteristics of tAML and sAML, highlighting commonalities and divergent features and discussed classification aspects. We also gathered the newest evidence of leukemogenic trajectories leading from bone marrow failure syndromes, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and MDS/MPN overlap syndromes to sAML, as well as leukemias arising from donors' cells in the setting of allogenic transplantation. Furthermore, we reviewed germline and acquired predisposition to leukemias and discussed the therapeutic landscape and future directions.