Figure 2.

History of the two siblings acute myeloid leukemia. Based on the data provided by next-generation sequencing (NGS) studies on the 2 patients, the leading hypothesis is that patient’s (Pt) #1 CD34⁺ stem cells harbored a DNMT3A mutation predisposing to genomic instability at the time of donation to his brother, Pt #2. Years later, these DNMT3A^mut CD34⁺ cells gave rise to a donor-derived acute myeloid leukemia (AML) in Pt #2, without acquiring further hits and hence with a myelodysplastic syndromes (MDS)-like pseudo-chronic clinical course (overall survival [OS] of 12.8 years); on the contrary, they acquired additional genomic aberrations in Pt #1, hence causing a rapidly progressing AML with a very short OS (1.2 years). MRD: minimal residual disease; HSCT: hematopoietic stem cell transplant; yrs: years; CHIP: clonal hematopoiesis of indeterminate potential.