Fig. 3.

Morphological and genetic evolution of case A7. A 55-year-old woman evaluated for cytopenia. She developed MDS with excess of blasts in transformation to AML 33 months later and underwent allo-SCT, but relapsed 26 months after allo-SCT with AML. a, b Biopsy month 0; a normocellular bone marrow (BM) biopsy without evidence of dysplasia and normal cytogenetics (hematoxylin and eosin (HE), 400× original magnification); b usual distribution of granulopoiesis (in red) and erythropoiesis demonstrated by naphthol-AS-D-chloroacetate esterase reaction (200×). c, d Biopsy month 33; c increase in middle-sized, interspersed blasts, diagnosed as MDS with excess of blasts in transition to AML (HE, 400×); d the blasts are positive for CD117 (immunoperoxidase, 400×). e, f Biopsy month 64 and after allo-SCT; e hypercellular BM with many blasts (HE, 400×), which are positive for CD34 (f immunoperoxidase, 600×). g Variant allele frequencies (VAF) of detected mutations in consecutive biopsies show in the first biopsy two mutations in DNMT3A and IDH1 with a VAF of 35 and 16%, respectively. The second biopsy reveals the same mutational spectrum, but with increased VAFs and after allo-SCT there are three more mutations in SRSF2 (4%), RUNX1 (7%), and DNMT3A (25%), and the known mutations also increased (DNMT3A 45%, IDH1 43%)