Fanconi anemia gene variants in therapy-related myeloid neoplasms

Therapy-related myeloid neoplasms (t-MN) include myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) occurring as a late effect of chemotherapy and/or radiotherapy for a primary malignancy or for autoimmune diseases.1, 2 The incidence of this complication has been raising in the past years because of the prolonged survival and the higher number of treated patients. Still, <5% of patients exposed to cytotoxic drugs and radiotherapy develop a t-MN, suggesting an underlying individual susceptibility. Primary malignancies most frequently associated to t-MN are breast cancer and lymphoproliferative diseases. Other recurrent clinical characteristics are presence of multiple primary neoplasms in the same individual and cancer familiarity.2 So far, higher frequency of single-nucleotide variants of detoxification and DNA-repair enzymes, alone or in association, have been reported in t-MN, but none has been validated as significant risk factor in large patient groups.3, 4, 5, 6