Human acute stem cell leukemia with multilineage differentiation potential via cascade activation of growth factor receptors by Ugo Testa, Giovanni F.

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Human acute stem cell leukemia with multilineage differentiation potential via cascade activation of growth factor receptors by Ugo Testa, Giovanni F. Torelli, Roberta Riccioni, Andrea Onetti Muta, Stefania Militi, Luciana Annino, Gualtiero Mariani, Anna Guarini, Sabina Chiaretti, Jerome Ritz, Franco Mandelli, Cesare Peschle, and Robin Foa Blood Volume 99(12):4634-4637 June 15, 2002 ©2002 by American Society of Hematology

Flow cytometric analysis of leukemic blasts and results of HGF receptor expression.(A) Flow cytometric analysis of leukemic blasts. Flow cytometric analysis of leukemic blasts and results of HGF receptor expression.(A) Flow cytometric analysis of leukemic blasts. Flow cytometry of leukemic blasts was performed by using a panel of monoclonal antibodies selected to define the stem cell leukemia phenotype. Representative results are shown. (B) Representative results on HGF receptor (HGFR) expression. Expression of flt3, c-kit, IL-6R, and IL-3Rα chain on leukemic blasts grown either in the absence of HGFs (control) or in the presence of FL, KL, or IL-3. Ugo Testa et al. Blood 2002;99:4634-4637 ©2002 by American Society of Hematology

Cell-growth and cell-cycle analysis of leukemic blasts and differentiation of leukemic blasts in liquid suspension culture supplemented with different HGFs.(A) Cell-growth analysis of leukemic blasts. Cell-growth and cell-cycle analysis of leukemic blasts and differentiation of leukemic blasts in liquid suspension culture supplemented with different HGFs.(A) Cell-growth analysis of leukemic blasts. Leukemic blasts were grown in liquid suspension cultures in the presence of different HGFs. Top panel: (○) control; (●) FL; (■) KL, and (▪) IL-3. Middle panel: (○) Epo, Tpo, M-CSF, and G-CSF; (●) IL-3, GM-CSF, Epo, Tpo, M-CSF, and G-CSF; (■) FL, IL-6, bFGF, IL-3, GM-CSF, Epo, Tpo, M-CSF, and G-CF; (▪) KL, IL-6, bFGF, IL-3, GM-CSF, Epo, Tpo, M-CSF, G-CSF. Bottom panel: (○) FL, IL-3, GM-CSF, Epo, Tpo, M-CSF, and G-CSF; (●) KL, IL-3, GM-CSF, Epo, Tpo, M-CSF, and G-CSF. Mean values of 3 independent experiments are shown. (B) Cell-cycle analysis of leukemic blasts. Leukemic blasts were grown for 5 days in liquid suspension in the presence of different HGFs. (a) Control; (b) KL; (c) FL; (d) Epo, Tpo, M-CSF, and G-CSF; (e) FL, Epo, Tpo, M-CSF, and G-CSF; (f) KL, Epo, Tpo, M-CSF, and G-CSF; (g) IL-3, GM-CSF, Epo, Tpo, M-CSF, and G-CSF; (h) FL, KL, IL-6, and bFGF; (i) KL, IL-6, and bFGF; (l) FL, IL-6, bFGF, IL-3, GM-CSF, Epo, Tpo, M-CSF, and G-CSF; and (m) KL, IL-6, bFGF, IL-3, GM-CSF, Epo, Tpo, M-CSF, and G-CSF. Mean + SD of 3 independent experiments is presented. *P < .05. **P < .01. (C) Differentiation of leukemic blasts in liquid suspension culture supplemented with different HGFs. Cells were identified on cytospins stained with May-Grünwald Giemsa and were classified as blasts, erythroid (E), monocytic (Mo), granulocytic (G), or megakaryocytic (MK) cells. (a) Control; (b) KL; (c) FL, KL, IL-6, and bFGF; (d) FL, IL-6, bFGF, IL-3, Epo, Tpo, M-CSF, and G-CSF; (e) KL, IL-6, bFGF, IL-3, Epo, Tpo, M-CSF, and G-CSF; (f) Epo, Tpo, M-CSF, and G-CSF; (g) KL, Epo, Tpo, M-CSF, and G-CSF; and (h) FL, Epo, Tpo, M-CSF, and G-CSF. A representative experiment is presented. Ugo Testa et al. Blood 2002;99:4634-4637 ©2002 by American Society of Hematology