Figure 6.

High HMGA2 mRNA levels in patients with PMF are correlated with either repressed MIRlet-7 expressions or mutations in PRC2 components. (A) Mutations in the patients with ET (N = 27) and PMF (N = 18). Black squares indicate no metaphase cells in the chromosomal analysis. (B) Correlations in the expression of MIRlet-7a, -7b, and -7c in granulocytes of the patients with ET and PMF. MIRlet-7a vs -7b, R = 0.70 (left); MIRlet-7a vs -7c, R = 0.74 (center); MIRlet-7b vs -7c, R = 0.85 (right) (R indicates correlation coefficients). (C) Correlations in the expression levels of MIRlet-7c and HMGA2 mRNA in the granulocytes of individual patients. The red lines indicate the lower (MIRlet-7c) or upper (HMGA2) limit of the normal range determined according to the data of the healthy controls (see “Materials and methods”). Red circles indicate the patients with mutations in PRC2-related EZH2 and ASXL1, and a rhomboid denotes a patient with monosomy 7 involving EZH2. (D) Immunostaining of biopsied BM. The nuclei of megakaryocytes from 2 PMF patients with high expression of HMGA2 were positively stained by anti-HMGA2 antibody; those of the ET patient with low expression of HMGA2 were not stained. The tissue from breast cancer, in which the nuclei of neoplastic cells were positively stained, was used as a positive control. Scale bars indicate 50 μm.