Fancc−/−;Fancg−/− hematopoietic stem cells undergo clonal evolution and malignant transformation in vivo. (A) Experimental design: Fancc−/−;Fancg−/− BMCs and isogenic WT competitor cells were co-transplanted into lethally irradiated recipient mice. Cells were transplanted at a 5:1 ratio (2.5 × 106 test cells and 0.5 × 106 competitor cells). Donor cells were collected from syngeneic 3-month-old mice. (B) Fluctuations of donor Fancc−/−;Fancg−/− cell chimerism were sequentially examined in peripheral blood of individual recipients, each symbol represents and individual recipient mouse (n = 7). (C) Mice reconstituted with BMCs from Fancc−/−;Fancg−/− mice showed abnormal bone marrow and spleen architecture 12 months after transplantation. Subpanels i and iii are from mouse 5 in panel B of this figure, with a chimerism of 38% at 12 months after transplantation. Subpanels ii, iv, and v are from mouse 2 in panel B of this figure.