Transplantation of vav-cre;Gata2fl/+ LSK into lethally-irradiated mice leads to BMF and leukemia. (A) Representative example of the transplantation assay performed with Gata2fl/+ and vav-Cre;Gata2fl/+ mice. Survival curves obtained after subjecting adult (B) and aged (C) Gata2fl/+ and vav-Cre;Gata2fl/+ mice to transplantation and followed over the time. Blue stars show the mice that succumbed due to leukemia. (D) Hematoxylin and eosin (H&E) staining performed on sternum obtained from donor and succumbed mice due to BMF leukemic and myelodysplasic mice at original magnification ×100 and original magnification ×400. (E) Analysis of the different BM-cell subsets from animals that succumbed due to BMF and leukemia compared to Gata2fl/+ mice. (F) GSEA of RNA-seq analysis of CD45.2+ BM cells from Gata2fl/+ and vav-Cre;Gata2fl/+ mice. X-axis indicates significance value. (G) H&E and CD3 IHC performed on spleen obtained from an adult succumbed mouse due to leukemia. (H) H&E staining performed on BM obtained from an aged succumbed mouse due to MDS. (I) WES and array-CGH analysis performed on BM samples obtained from succumbed animals due to BMF, leukemia, and MDS. ∗P < .05. CGH, comparative genomic hybridisation; Ctrl, control; IHC, immunohistochemistry; Leuk, leukemia; NB, number of genes in the leading edge of GSEA; WES, whole exome sequencing.

Transplantation of vav-cre;Gata2fl/+ LSK into lethally-irradiated mice leads to BMF and leukemia. (A) Representative example of the transplantation assay performed with Gata2fl/+ and vav-Cre;Gata2fl/+ mice. Survival curves obtained after subjecting adult (B) and aged (C) Gata2fl/+ and vav-Cre;Gata2fl/+ mice to transplantation and followed over the time. Blue stars show the mice that succumbed due to leukemia. (D) Hematoxylin and eosin (H&E) staining performed on sternum obtained from donor and succumbed mice due to BMF leukemic and myelodysplasic mice at original magnification ×100 and original magnification ×400. (E) Analysis of the different BM-cell subsets from animals that succumbed due to BMF and leukemia compared to Gata2fl/+ mice. (F) GSEA of RNA-seq analysis of CD45.2+ BM cells from Gata2fl/+ and vav-Cre;Gata2fl/+ mice. X-axis indicates significance value. (G) H&E and CD3 IHC performed on spleen obtained from an adult succumbed mouse due to leukemia. (H) H&E staining performed on BM obtained from an aged succumbed mouse due to MDS. (I) WES and array-CGH analysis performed on BM samples obtained from succumbed animals due to BMF, leukemia, and MDS. ∗P < .05. CGH, comparative genomic hybridisation; Ctrl, control; IHC, immunohistochemistry; Leuk, leukemia; NB, number of genes in the leading edge of GSEA; WES, whole exome sequencing.

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