PMC

Analysis of a patient-derived xenograft from a KRAS^G12S-mutant patient with ECD. (A) Fludeoxyglucose positron emission tomography (FDG-PET) imaging and histologic and immunohistochemical analysis of the KRAS^G12S-mutant ECD patient’s heart biopsy specimen (scale bars represent 200 µm). (B) Flow cytometric analysis of BM, spleen, liver, and lung of recipient NSGS mouse 90 days postxenotransplantation with CD34⁺ cells from the same KRAS^G12S-mutant ECD patient. (C) Histologic and immunohistochemical analysis of engrafted tissue from the recipient mouse (scale bars represent 200 µm). (D) Sanger sequencing of genomic DNA from hCD45⁺ cells purified from recipient mouse BM (left) and spleen (right) revealing a KRAS^G12S mutation in engrafted human hematopoietic cells. H&E, hematoxylin and eosin.

The BRAF^V600Emutation is detectable in mature and immature hematopoietic cells from patients with histiocytosis. (A) Percentage of patients for whom BRAF^V600E mutation was detected in mature PB cells. (B) BRAF^V600E mutant allele frequency in fluorescence-activated cell sorting–purified cells from the BM or PB of 5 histiocytosis patients. ND indicates populations not studied. Patient numbering per supplemental Table 1. (C) Percentage of patients for whom the BRAF^V600E mutation was detected in CD34⁺ BM cells or in CD34-derived CFU-M, CFU-G, BFU-E, and plasmacytoid DCs (pDC) or mDCs. (D) BRAF^V600E, TET2^L1819X, and SRSF2^L95P status of 20 colonies derived from single CD34⁺ BM cells of a patient with BRAF^V600E-mutant MH (#P10). The results suggest that histiocytosis and AMML cells of this patient derived from a common TET2-mutated HSPC. In panels A and C, each denominator indicates the total number of patients for whom results were obtained.