Molecular characterization of both cases failed to identify fusion transcripts involving MLL or PLZF-RARA and no collaborating somatic mutations commonly found among MDS patients were seen in either case, suggesting the presence of an as yet unidentified oncogenic fusion protein.
Development and progression of MDS to acute myeloid leukemia is suggested to be a multistep alteration to hematopoietic stem cells consisting of class I and class II alterations: the former targeting genes that are involved in signal transduction (e.g., FLT3, RAS and KIT), whereas the latter affect transcription factors (e.g., RUNX, RARA, EVI1 and WT1).
The MLF1 and RARA genes are fused with NPM1 in myelodysplastic syndrome and acute myeloid leukemia (AML) with t(3;5) and acute promyelocytic leukemia with t(5;17), respectively.