Figure 1
GAB2 is required for induction of CML-like MPN by BCR-ABL1. (A) Kaplan-Meier (K-M) survival curves for recipients of BM from Gab2−/− donors in the Balb/c background (>F9 generation backcross) transduced with p210MIGFP (red line, n = 7) or p210Y177FMIGFP (blue dotted line, n = 7) retrovirus and from wild-type Balb/c donors (blue solid line, n = 5) transduced with p210MIGFP retrovirus. Symbols represent individual mice (squares for recipients of Gab2+/+ BM, circles for recipients of Gab2−/− BM); disease phenotype is indicated by shading (black, CML-like MPN; white, B-ALL; gray, T-ALL). For p210MIGFP-transduced BM, the difference in survival between the Gab2−/− and Gab2+/+ recipient cohorts was significant (P = .0003, Wilcoxon test). There was no significant survival difference between recipients of p210MIGFP-transduced Gab2−/− BM and p210Y177FMIGFP-transduced Gab2+/+ BM (P = .058). (B) Scatter plot of PBL counts in the 3 cohorts from the transplants in A at various times after transplantation. The cross indicates death of a recipient of p210MIGFP-transduced Gab2+/+ BM. Note the attenuated and nonfatal leukocytosis induced in recipients of p210Y177FMIGFP-transduced Gab2+/+ BM. (C) Flow cytometric plot of expression of GFP (x-axis) and the myeloid marker Mac-1 (y-axis) in PBLs from 2 representative recipients of p210MIGFP-transduced BM from Gab2−/− donors (left) and from a recipient of p210MIGFP-transduced Gab2+/+ BM with CML-like MPN (right), obtained 1 month after transplantation.

GAB2 is required for induction of CML-like MPN by BCR-ABL1. (A) Kaplan-Meier (K-M) survival curves for recipients of BM from Gab2−/− donors in the Balb/c background (>F9 generation backcross) transduced with p210MIGFP (red line, n = 7) or p210Y177FMIGFP (blue dotted line, n = 7) retrovirus and from wild-type Balb/c donors (blue solid line, n = 5) transduced with p210MIGFP retrovirus. Symbols represent individual mice (squares for recipients of Gab2+/+ BM, circles for recipients of Gab2−/− BM); disease phenotype is indicated by shading (black, CML-like MPN; white, B-ALL; gray, T-ALL). For p210MIGFP-transduced BM, the difference in survival between the Gab2−/− and Gab2+/+ recipient cohorts was significant (P = .0003, Wilcoxon test). There was no significant survival difference between recipients of p210MIGFP-transduced Gab2−/− BM and p210Y177FMIGFP-transduced Gab2+/+ BM (P = .058). (B) Scatter plot of PBL counts in the 3 cohorts from the transplants in A at various times after transplantation. The cross indicates death of a recipient of p210MIGFP-transduced Gab2+/+ BM. Note the attenuated and nonfatal leukocytosis induced in recipients of p210Y177FMIGFP-transduced Gab2+/+ BM. (C) Flow cytometric plot of expression of GFP (x-axis) and the myeloid marker Mac-1 (y-axis) in PBLs from 2 representative recipients of p210MIGFP-transduced BM from Gab2−/− donors (left) and from a recipient of p210MIGFP-transduced Gab2+/+ BM with CML-like MPN (right), obtained 1 month after transplantation.

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