Figure 1.
Recurrent activating PIK3CA mutations drives histiocytic neoplasms in vivo. (A) Diagram of PIK3CA alterations across cancer showing hotspots in the helical and kinase domains, the locations of activating mutations. (B) Protein diagram summarizing recurrent PIK3CA mutations across histiocytic neoplasm subtypes. (C) Kaplan-Meier curve of primary CD11c-cre Pik3caH1047R and littermate Pik3ca control mice; n = 15-20 mice; ∗∗∗∗P < .0001. Log-rank (Mantel-Cox) test. (D) Representative histological images of bone marrow showing trilineage hematopoiesis in control mice with no evidence of histiocytosis compared with the bone marrow of CD11c-cre Pik3caH1047R that shows involvement of the bone marrow by increased CD68+, large, foamy histiocytes, and multinucleated giant cells reminiscent of a human histiocytic neoplasm (H&E stain and murine CD68 immunohistochemistry; 600× magnification). (E) Bar plots of percentage of B- (B220+) and T- (CD3+) lymphocytes among CD45+ cells in blood (left), bone marrow (middle), and spleen (right) in control vs mutant mice by flow cytometry. (F) As in panel E but for myelomonocytic (CD11b+) and dendritic (CD11c+ MHCII+) cells in blood. (G) Box-and-whisker plots of hemoglobin in mice. Mean ± SD. n = 3 mice; ∗P<.01; 1-way ANOVA. ANOVA, analysis of variance; H&E, hematoxylin and eosin; SD, standard deviation.

Recurrent activating PIK3CA mutations drives histiocytic neoplasms in vivo. (A) Diagram of PIK3CA alterations across cancer showing hotspots in the helical and kinase domains, the locations of activating mutations. (B) Protein diagram summarizing recurrent PIK3CA mutations across histiocytic neoplasm subtypes. (C) Kaplan-Meier curve of primary CD11c-cre Pik3caH1047R and littermate Pik3ca control mice; n = 15-20 mice; ∗∗∗∗P < .0001. Log-rank (Mantel-Cox) test. (D) Representative histological images of bone marrow showing trilineage hematopoiesis in control mice with no evidence of histiocytosis compared with the bone marrow of CD11c-cre Pik3caH1047R that shows involvement of the bone marrow by increased CD68+, large, foamy histiocytes, and multinucleated giant cells reminiscent of a human histiocytic neoplasm (H&E stain and murine CD68 immunohistochemistry; 600× magnification). (E) Bar plots of percentage of B- (B220+) and T- (CD3+) lymphocytes among CD45+ cells in blood (left), bone marrow (middle), and spleen (right) in control vs mutant mice by flow cytometry. (F) As in panel E but for myelomonocytic (CD11b+) and dendritic (CD11c+ MHCII+) cells in blood. (G) Box-and-whisker plots of hemoglobin in mice. Mean ± SD. n = 3 mice; ∗P<.01; 1-way ANOVA. ANOVA, analysis of variance; H&E, hematoxylin and eosin; SD, standard deviation.

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