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Figure 3. Low level or absence of Gfi1b accelerates the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML) in the NUP98/HOXD13 MDS mouse model. (A) Crossing of the Gfi1bwt/wt and Gfi1bEGFP/wt mouse strains with the NUP98/HOXD13 mouse model. (B) Survival of Gfi1bwt/wt and Gfi1bEGFP/wtNUP98/HOXD13 transgenic mice; P=0.0039. Number of mice succumbing to AML is indicated. (C) Mean fluorescence intensity (MFI) of the GFP expression level (and hence Gfi1b promoter activity) in Gfi1bEGFP/wt mice that died of AML before 250 days (n=7) or after 250 days (n=5); P=0.0272. (D) Wright-Giemsa staining of bone marrow (BM) cytospins from representative Gfi1bEGFP/wt and Gfi1bwt/wt NUP98/HOXD13 leukemic mice (bar=20 mm). (E) Crossing of the Gfi1bfl/flMxCrewt and Gfi1bfl/flMxCretg mouse strains with the NUP98/HOXD13 mouse model. After Cre-mediated deletion of the Gfi1b gene upon poly(I:C) administration, the mice were monitored for signs of leukemia. (F) Survival of Gfi1bfl/flMxCrewt (Gfi1bwt/wt) and Gfi1bfl/flMxCretg (Gfi1bKO/KO) mice transgenically expressing NUP98/HOXD13 after poly(I:C) administration; P<0.0001. Number of mice succumbing to AML is indicated. (G) Polymerase chain reaction genotyping of DNA from BM cells of poly(I:C)-injected Gfi1bfl/flMxCrewt and Gfi1bfl/flMxCretg NUP98/HOXD13 leukemic mice. (H) Wright-Giemsa staining of BM cytospins from representative poly(I:C)-injected Gfi1bfl/flMxCrewt and Gfi1bfl/flMxCretgNUP98/HOXD13 leukemic mice (bar=20 mm). (I) The frequency of monocytes (Mac-1hiGr-1int) (left panel, ****P<0.0001), granulocytes (Mac- 1hiGr-1hi) (middle panel, *P=0.0206) and CD117+ (c-Kit) cells (right panel, ****P<0.0001) in the BM of mice described in (F) (n=15 for Gfi1bfl/flMxCrewt mice; n=13 for Gfi1bfl/flMxCretgNUP98/HOXD13 mice).
haematologica | 2018; 103(4)