Figure 4
Figure 4. Selectin ligands on BCR-ABL1–expressing leukemic stem cells contribute to engraftment. (A-B) Kaplan-Meier curves for (A) mortality due to CML-like leukemia and (B) overall survival of B6129 F2 WT recipients of BCR-ABL1–transduced BM from B6129 F2 WT control (solid line, n = 33), PSGL-1 KO (Selplg−/−; dotted line, n = 8), and PSGL-1/CD44 double KO (Selplg−/−Cd44−/−; dashed line, n = 14) donors. Only 5 of 8 recipients of PSGL-1–deficient BM developed CML-like leukemia. Two mice succumbed at 127 days after transplant to BCR-ABL1–induced T-cell acute lymphoblastic leukemia, whereas another died of delayed graft failure (see text). The overall survival of PSGL-1 KO recipients was not significantly different from recipients of BCR-ABL1–transduced WT BM. (C) Deficiency of PSGL-1 and CD44 in donor BM leads to decreased engraftment of BCR-ABL1–induced CML-like leukemia. Southern blot of genomic DNA from BM of recipients of BCR-ABL1-transduced WT (lanes 2-11) and PSGL-1/CD44 double KO (lanes 12-22) donor BM, hybridized with a GFP probe. Recipients in lanes 6 and 15 to 21 did not develop clinical disease, whereas the recipient in lane 22 succumbed to histiocytic sarcoma. *Background bands. (D-E) Kaplan-Meier curves for (D) mortality due to CML-like leukemia and (E) overall survival for WT recipients of WT (solid line, n = 33), Core2GlcNAcT-I KO (Gcnt1−/−; dashed line, n = 6), and FucT-IV/FucT-VII double KO (Fut4−/−/Fut7−/−; dotted line, n = 6) BCR-ABL1–transduced BM. The difference in survival between recipients of WT and FucT-IV/FucT-VII double KO BM was of borderline significance (P = .13, Mantel-Cox test), whereas that of Core2GlcNAcT-I KO recipients was not. One recipient in the FucT-IV/FucT-VII double KO cohort had circulating BCR-ABL1–expressing myeloid cells early after transplant, but these leukocytes disappeared, and the animal ultimately engrafted with BCR-ABL1– cells (data not shown). (F) Donor Core-2 and Fuc-T IV/VII deficiency leads to a reduction of clonality of CML-like leukemia. Genomic DNA from the indicated tissues was analyzed by Southern blot as in Figure 2B. Lanes 5 to 8 and 9 to 12, respectively, contain the samples of WT recipients of BCR-ABL1–transduced Core-2 KO or Fuc-T IV/VII double KO BM. Note the reduction of clonality in lanes 5 to 12 to 1 or 2 clones. Proviral copy number is indicated below.

Selectin ligands on BCR-ABL1–expressing leukemic stem cells contribute to engraftment. (A-B) Kaplan-Meier curves for (A) mortality due to CML-like leukemia and (B) overall survival of B6129 F2 WT recipients of BCR-ABL1–transduced BM from B6129 F2 WT control (solid line, n = 33), PSGL-1 KO (Selplg−/−; dotted line, n = 8), and PSGL-1/CD44 double KO (Selplg−/−Cd44−/−; dashed line, n = 14) donors. Only 5 of 8 recipients of PSGL-1–deficient BM developed CML-like leukemia. Two mice succumbed at 127 days after transplant to BCR-ABL1–induced T-cell acute lymphoblastic leukemia, whereas another died of delayed graft failure (see text). The overall survival of PSGL-1 KO recipients was not significantly different from recipients of BCR-ABL1–transduced WT BM. (C) Deficiency of PSGL-1 and CD44 in donor BM leads to decreased engraftment of BCR-ABL1–induced CML-like leukemia. Southern blot of genomic DNA from BM of recipients of BCR-ABL1-transduced WT (lanes 2-11) and PSGL-1/CD44 double KO (lanes 12-22) donor BM, hybridized with a GFP probe. Recipients in lanes 6 and 15 to 21 did not develop clinical disease, whereas the recipient in lane 22 succumbed to histiocytic sarcoma. *Background bands. (D-E) Kaplan-Meier curves for (D) mortality due to CML-like leukemia and (E) overall survival for WT recipients of WT (solid line, n = 33), Core2GlcNAcT-I KO (Gcnt1−/−; dashed line, n = 6), and FucT-IV/FucT-VII double KO (Fut4−/−/Fut7−/−; dotted line, n = 6) BCR-ABL1–transduced BM. The difference in survival between recipients of WT and FucT-IV/FucT-VII double KO BM was of borderline significance (P = .13, Mantel-Cox test), whereas that of Core2GlcNAcT-I KO recipients was not. One recipient in the FucT-IV/FucT-VII double KO cohort had circulating BCR-ABL1–expressing myeloid cells early after transplant, but these leukocytes disappeared, and the animal ultimately engrafted with BCR-ABL1– cells (data not shown). (F) Donor Core-2 and Fuc-T IV/VII deficiency leads to a reduction of clonality of CML-like leukemia. Genomic DNA from the indicated tissues was analyzed by Southern blot as in Figure 2B. Lanes 5 to 8 and 9 to 12, respectively, contain the samples of WT recipients of BCR-ABL1–transduced Core-2 KO or Fuc-T IV/VII double KO BM. Note the reduction of clonality in lanes 5 to 12 to 1 or 2 clones. Proviral copy number is indicated below.

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