Molecular and clinical characteristics of patients with TN-PMF. (A-D) Representative BM seriated sections from 2 patients with TN-PMF, stained with H&E (A,C) and reticulin stain (B,D). Fibrosis with osteomyelosclerosis and megakaryocyte hyperplasia (with cluster formation and atypical forms) associated with fibrosis grade 3 are shown in panels A and B and in panels C and D, respectively. Bars: 500 μm in panels A and B, and 200 μm in panels C and D. (E) Oncoprint reporting the somatic mutations identified in the TN-PMF cohort. The orange and green bars highlight the patients with SETBP1-positive and -negative disease, respectively. (F) Kaplan-Meier survival analysis. Patients with TN-PMF were stratified according to the somatic mutational burden, with SETBP1-positive cases shown in orange and patients with SETBP1-negative disease shown in green. The log-rank test was used to test for differences in survival between the 2 groups. Tick marks indicate censored data. (G-I) Fish plots showing somatic evolution of the disease in 3 patients with TN-PMF. In 2 cases (G,I), a late acquisition of homozygous SETBP1 mutation is observed. (J) Neutrophil and lymphocyte populations in the PB from homozygous (homo) and heterozygous (het) SETBP1G870S mice. (K) H&E staining of the PB from a 30-day-old homozygous SETBP1G870S mouse showing accumulation of mature granulocytes.
