Figure 3.

Modulation of TGFβRI on leukemic cells differentially affects BCR-ABL1⁺ (chronic) and MLL-AF9⁺ (acute) myeloid neoplasms in a Col1-caPPR microenvironment. (a) Survival curves for WT or Col1-caPPR recipients of BCR-ABL1-transduced WT BM that was co-transduced with lentivirus expressing either scrambled shRNA (WT: solid line; Col1-caPPR: dotted line) or Tgfbr1 shRNA (WT: long dashes; Col1-caPPR: short dashes). Survival of Col1-caPPR recipients of BCR-ABL1⁺ Tgfbr1 shRNA⁺ BM was significantly shortened (P = 0.007, logrank test) compared to Col1-caPPR recipients of BCR-ABL1⁺ scrambled shRNA⁺ BM. All Col1-caPPR recipients of BCR-ABL1⁺ Tgfbr1 shRNA⁺ BM succumbed to CML-like MPN. (b) Survival curves for WT or Col1-caPPR recipients of WT BM transduced with MLL-AF9 retrovirus alone (WT: solid line; Col1-caPPR: dotted line) or co-transduced with a retrovirus expressing TGFβRI (WT: long dashes; Col1-caPPR: short dashes). Survival of Col1-caPPR recipients of MLL-AF9⁺ TGFβRI⁺ BM (n=10) was significantly prolonged (P = 0.02, logrank test) compared to Col1-caPPR recipients of BM transduced with MLL-AF9 only (n=8). (c) pSMAD2/3 immunofluorescence staining of Lin⁻ MLL-AF9⁺ (left) or BCR-ABL1⁺ KLS cells treated in vitro with 5 ng/ml TGF-β1 (bottom) or saline (top). (d) Quantitation of individual cells from c by confocal microscopy. pSMAD2/3 staining was significantly increased in CML-initiating cells treated with TGF-β1 compared to saline-treated cells (P = 0.01, t-test), but not in AML-initiating cells.