Getting to the stem of chronic myeloid leukaemia (original) (raw)
Nowell, P. & Hungerford, D. A minute chromosome in human chronic granulocytic leukemia. Science132, 1497–1499 (1960). Google Scholar
Bartram, C. R. et al. Translocation of c-ab1 oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature306, 277–280 (1983). ArticleCASPubMed Google Scholar
Frank, D. A. & Varticovski, L. BCR/abl leads to the constitutive activation of Stat proteins, and shares an epitope with tyrosine phosphorylated Stats. Leukemia10, 1724–1730 (1996). CASPubMed Google Scholar
Krebs, D. L. & Hilton, D. J. SOCS proteins: negative regulators of cytokine signaling. Stem Cells19, 378–387 (2001). ArticleCASPubMed Google Scholar
Neshat, M. S., Raitano, A. B., Wang, H. G., Reed, J. C. & Sawyers, C. L. The survival function of the Bcr–Abl oncogene is mediated by Bad-dependent and -independent pathways: roles for phosphatidylinositol 3-kinase and Raf. Mol. Cell Biol.20, 1179–1186 (2000). ArticleCASPubMedPubMed Central Google Scholar
Neubauer, H. et al. Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell93, 397–409 (1998). ArticleCASPubMed Google Scholar
Sattler, M. et al. Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell1, 479–492 (2002). ArticleCASPubMed Google Scholar
Sattler, M. et al. BCR/ABL directly inhibits expression of SHIP, an SH2-containing polyinositol-5-phosphatase involved in the regulation of hematopoiesis. Mol. Cell Biol.19, 7473–7480 (1999). ArticleCASPubMedPubMed Central Google Scholar
Kantarjian, H. M., Talpaz, M., Giles, F., O'Brien, S. & Cortes, J. New insights into the pathophysiology of chronic myeloid leukemia and imatinib resistance. Ann. Intern. Med.145, 913–923 (2006). ArticlePubMed Google Scholar
Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR–ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med.344, 1031–1037 (2001). ArticleCASPubMed Google Scholar
Einhorn, L. H. & Williams, S. D. The role of _cis_-platinum in solid-tumor therapy. N. Engl. J. Med.300, 289–291 (1979). ArticleCASPubMed Google Scholar
Goldman, J., Gordon, M. Why do chronic myelogenous leukemia stem cells survive allogeneic stem cell transplantation or imatinib: does it really matter? Leuk. Lymphoma47, 1–7 (2006). ArticleCASPubMed Google Scholar
Hughes, T. P. et al. Frequency of major molecular responses to imatinib or interferon α plus cytarabine in newly diagnosed chronic myeloid leukemia. N. Engl. J. Med.349, 1423–1432 (2003). This was the first large analysis to reveal lack of complete molecular response in majority of cytogenetic responses. ArticleCASPubMed Google Scholar
Druker, B. J. et al. Five-year follow-up of patients receiving imatinib for chronic myelogenous leukemia. N. Engl. J. Med.355, 2408–2417 (2006). ArticleCASPubMed Google Scholar
Roy, L. et al. Survival advantage from imatinib compared with the combination interferon-α plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials. Blood108, 1478–1484 (2006). ArticleCASPubMed Google Scholar
Deininger, M. W., Goldman, J. M. & Melo, J. V. The molecular biology of chronic myeloid leukemia. Blood96, 3343–3356 (2000). ArticleCASPubMed Google Scholar
Jiang, X., Saw, K. M., Eaves, A. & Eaves, C. Instability of BCR–ABL gene in primary and cultured chronic myeloid leukemia stem cells. J. Natl Cancer Inst.99, 680–693 (2007). ArticleCASPubMed Google Scholar
Roche-Lestienne, C. et al. Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. Blood100, 1014–1018 (2002). ArticleCASPubMed Google Scholar
Hochhaus, A. et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood109, 2303–2309 (2007). ArticleCASPubMed Google Scholar
le Coutre, P. et al. Nilotinib (formerly AMN107), a highly selective BCR–ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood111, 1834–1839 (2008). ArticleCASPubMed Google Scholar
Cortes, J., O'Brien, S. & Kantarjian, H. Discontinuation of imatinib therapy after achieving a molecular response. Blood104, 2204–2205 (2004). ArticleCASPubMed Google Scholar
Usuki, K., Iijima, K., Iki, S. & Urabe, A. CML cytogenetic relapse after cessation of imatinib therapy. Leuk. Res.29, 237–238 (2005). ArticleCASPubMed Google Scholar
Piazza, R. G. et al. Imatinib dose increase up to 1200 mg daily can induce new durable complete cytogenetic remissions in relapsed Ph+ chronic myeloid leukemia patients. Leukemia19, 1985–1987 (2005). ArticleCASPubMed Google Scholar
Kantarjian, H. et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood103, 2873–2878 (2004). ArticleCASPubMed Google Scholar
Talpaz, M. et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N. Engl. J. Med.354, 2531–2541 (2006). ArticleCASPubMed Google Scholar
Kantarjian, H. et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N. Engl. J. Med.354, 2542–2551 (2006). ArticlePubMed Google Scholar
Kaeda, J., Chase, A. & Goldman, J. M. Cytogenetic and molecular monitoring of residual disease in chronic myeloid leukaemia. Acta Haematol.107, 64–75 (2002). ArticleCASPubMed Google Scholar
Kiel, M. J., He, S., Ashkenazi R., et al. Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature449, 238–242 (2007). ArticleCASPubMedPubMed Central Google Scholar
Morrison, S. J., Hemmati, H. D., Wandycz, A. M. & Weissman, I. L. The purification and characterization of fetal liver hematopoietic stem cells. Proc. Natl Acad. Sci. USA92, 10302–10306 (1995). ArticleCASPubMedPubMed Central Google Scholar
Murray, L. et al. Enrichment of human hematopoietic stem cell activity in the CD34+Thy-1+Lin− subpopulation from mobilized peripheral blood. Blood85, 368–378 (1995). ArticleCASPubMed Google Scholar
Uchida, N. & Weissman, I. L. Searching for hematopoietic stem cells: evidence that Thy-1.1lo Lin−Sca-1+ cells are the only stem cells in C57BL/Ka-Thy-1.1 bone marrow. J. Exp. Med.175, 175–184 (1992). One of a series of seminal early studies that edified the concept that flow cytometry could be used to prospectively isolate haematopoietic stem cells. ArticleCASPubMed Google Scholar
Kiel, M. J. et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell121, 1109–1121 (2005). ArticleCASPubMed Google Scholar
Wolf, N. S., Kone, A., Priestley, G. V. & Bartelmez SH . In vivo and in vitro characterization of long-term repopulating primitive hematopoietic cells isolated by sequential Hoechst 33342-rhodamine 123 FACS selection. Exp. Hematol.21, 614–622 (1993). CASPubMed Google Scholar
Morrison, S. J., Uchida, N. & Weissman, I. L. The biology of hematopoietic stem cells. Annu. Rev. Cell Dev. Biol.11, 35–71 (1995). ArticleCASPubMed Google Scholar
Hogan, C. J., Shpall, E. J. & Keller, G. Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice. Proc. Natl Acad. Sci. USA99, 413–418 (2002). ArticleCASPubMedPubMed Central Google Scholar
Dick, J. E., Bhatia, M., Gan, O., Kapp, U. & Wang, J. C. Assay of human stem cells by repopulation of NOD/SCID mice. Stem Cells15 (Suppl. 1), 199–203; discussion 204–207 (1997). ArticlePubMed Google Scholar
McKenzie, J. L., Gan, O. I., Doedens, M., Wang, J. C. & Dick, J. E. Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment. Nature Immunol.7, 1225–1233 (2006). ArticleCAS Google Scholar
Hogge, D. E., Lansdorp, P. M., Reid, D., Gerhard, B. & Eaves, C. J. Enhanced detection, maintenance, and differentiation of primitive human hematopoietic cells in cultures containing murine fibroblasts engineered to produce human steel factor, interleukin-3, and granulocyte colony-stimulating factor. Blood88, 3765–3773 (1996). ArticleCASPubMed Google Scholar
Baum, C. M., Weissman, I. L., Tsukamoto, A. S., Buckle, A. M. & Peault, B. Isolation of a candidate human hematopoietic stem-cell population. Proc. Natl Acad. Sci. USA89, 2804–2808 (1992). ArticleCASPubMedPubMed Central Google Scholar
Yin, A. H. et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood90, 5002–5012 (1997). ArticleCASPubMed Google Scholar
Moreb, J. S. et al. Interleukin-1 and tumor necrosis factor alpha induce class 1 aldehyde dehydrogenase mRNA and protein in bone marrow cells. Leuk. Lymphoma20, 77–84 (1995). ArticleCASPubMed Google Scholar
McKenzie, J. L., Takenaka, K., Gan, O. I., Doedens, M. & Dick, J. E. Low Rhodamine123 retention identifies long-term human hematopoietic stem cells within the Lin−CD34+CD38- population. Blood109, 543–545 (2006). ArticlePubMedCAS Google Scholar
Jamieson, C. H. et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N. Engl. J. Med.351, 657–667 (2004). Jamiesonet al. redefined the cancer stem cell model by illustrating the presence of stem cell-like qualities in committed progenitors of advanced disease. ArticleCASPubMed Google Scholar
Cammenga, J. Gatekeeper pathways and cellular background in the pathogenesis and therapy of AML. Leukemia19, 1719–1728 (2005). ArticleCASPubMed Google Scholar
Huntly, B. J. & Gilliland, D. G. Leukaemia stem cells and the evolution of cancer-stem-cell research. Nature Rev. Cancer5, 311–321 (2005). ArticleCAS Google Scholar
Bonnet, D. & Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Med.3, 730–737 (1997). Leukaemic C34+CD38−cells were shown to have preferential capacity to recapitulate leukaemia in a xenograft transplantation model. ArticleCASPubMed Google Scholar
Reya, T., Morrison, S. J., Clarke, M. F. & Weissman, I. L. Stem cells, cancer, and cancer stem cells. Nature414, 105–111 (2001). ArticleCASPubMed Google Scholar
Hope, K. J., Jin, L. & Dick, J. E. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nature Immunol.5, 738–743 (2004). ArticleCAS Google Scholar
Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J. & Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl Acad. Sci. USA100, 3983–3988 (2003). ArticleCASPubMedPubMed Central Google Scholar
Singh, S. K., Clarke, I. D., Hide, T. & Dirks, P. B. Cancer stem cells in nervous system tumors. Oncogene23, 7267–7273 (2004). ArticleCASPubMed Google Scholar
O'Brien, C. A., Pollett, A., Gallinger, S. & Dick, J. E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature445, 106–110 (2007). ArticleCASPubMed Google Scholar
Prince, M. E. et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc. Natl Acad. Sci. USA104, 973–978 (2007). ArticleCASPubMedPubMed Central Google Scholar
Li, C. et al. Identification of pancreatic cancer stem cells. Cancer Res.67, 1030–1037 (2007). ArticleCASPubMed Google Scholar
Guzman, M. L. et al. Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1, 2, 4-thiadiazolidine, 3, 5 dione (TDZD-8). Blood110, 4436–4444 (2007). ArticleCASPubMedPubMed Central Google Scholar
Guzman, M. L. et al. An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells. Blood110, 4427–4435 (2007). ArticleCASPubMedPubMed Central Google Scholar
Yilmaz, O. H. et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature441, 475–482 (2006). ArticleCASPubMed Google Scholar
Fialkow, P. J., Jacobson, R. J. & Papayannopoulou, T. Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. Am. J. Med.63, 125–130 (1977). A seminal work from 1977 that recognized that CML was a clonal disease. ArticleCASPubMed Google Scholar
Udomsakdi, C. et al. Rapid decline of chronic myeloid leukemic cells in long-term culture due to a defect at the leukemic stem cell level. Proc. Natl Acad. Sci. USA89, 6192–6196 (1992). ArticleCASPubMedPubMed Central Google Scholar
Jaiswal, S. et al. Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias. Proc. Natl Acad. Sci. USA100, 10002–10007 (2003). ArticleCASPubMedPubMed Central Google Scholar
Jiang, X., Lopez, A., Holyoake, T., Eaves, A. & Eaves, C. Autocrine production and action of IL-3 and granulocyte colony-stimulating factor in chronic myeloid leukemia. Proc. Natl Acad. Sci. USA96, 12804–12809 (1999). ArticleCASPubMedPubMed Central Google Scholar
Jordan, C. T. & Guzman, M. L. Mechanisms controlling pathogenesis and survival of leukemic stem cells. Oncogene23, 7178–7187 (2004). ArticleCASPubMed Google Scholar
Copland, M., Hamilton, A. & Holyoake, T. L. Response: Conventional Western blotting techniques will not reliably quantify p210 BCR–ABL. Blood109, 1336 (2007). ArticleCAS Google Scholar
Jiang, X. et al. Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR–ABL targeted therapies. Leukemia21, 926–935 (2007). ArticleCASPubMed Google Scholar
Chu, S. et al. Detection of BCR–ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment. Blood105, 2093–2098 (2005). ArticleCASPubMed Google Scholar
Gorre, M. E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR–ABL gene mutation or amplification. Science293, 876–880 (2001). ArticleCASPubMed Google Scholar
Jorgensen, H. G. et al. Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in vitro. Leukemia19, 1184–1191 (2005). ArticleCASPubMed Google Scholar
Copland, M. et al. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML, but does not eliminate the quiescent fraction. Blood107, 4532–4539 (2006). ArticleCASPubMed Google Scholar
Graham, S. M. et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood99, 319–325 (2002). ArticleCASPubMed Google Scholar
Copland, M., Fraser, A. R., Harrison, S. J. & Holyoake, T. L. Targeting the silent minority: emerging immunotherapeutic strategies for eradication of malignant stem cells in chronic myeloid leukaemia. Cancer Immunol. Immunother.54, 297–306 (2005). ArticleCASPubMed Google Scholar
Copland, M., Jorgensen, H. G. & Holyoake, T. L. Evolving molecular therapy for chronic myeloid leukaemia — are we on target? Hematology10, 349–359 (2005). ArticleCASPubMed Google Scholar
Deininger, M. et al. No evidence for persistence of BCR–ABL-positive cells in patients in molecular remission after conventional allogenic transplantation for chronic myeloid leukemia. Blood96, 779–780 (2000). ArticleCASPubMed Google Scholar
Shah, N. P. et al. Multiple BCR–ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell2, 117–125 (2002). ArticleCASPubMed Google Scholar
Al-Ali, H. K. et al. High incidence of BCR–ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib. Hematol. J.5, 55–60 (2004). ArticleCASPubMed Google Scholar
Azam, M., Latek, R. R. & Daley, G. Q. Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR–ABL. Cell112, 831–843 (2003). ArticleCASPubMed Google Scholar
Corbin, A. S., La Rosee, P., Stoffregen, E. P., Druker, B. J. & Deininger, M. W. Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood101, 4611–4614 (2003). ArticleCASPubMed Google Scholar
Nagar, B. et al. Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Res.62, 4236–4243 (2002). CASPubMed Google Scholar
Schindler, T. et al. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science289, 1938–1942 (2000). ArticleCASPubMed Google Scholar
Morel, F. et al. Double minutes containing amplified BCR–ABL fusion gene in a case of chronic myeloid leukemia treated by imatinib. Eur. J. Haematol.70, 235–239 (2003). ArticlePubMed Google Scholar
Shah, N. P. et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science305, 399–401 (2004). ArticleCASPubMed Google Scholar
Bartholomeusz, G. A. et al. Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells. Blood109, 3470–3478 (2007). ArticleCASPubMedPubMed Central Google Scholar
Cong, P. et al. IPI-504, a novel, orally active HSP90 inhibitor, prolongs survival of mice with BCR–ABL T315I CML and B-ALL. Blood108, Abstract 2183 (2006). Article Google Scholar
Giles, F. J. et al. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR–ABL mutation. Blood109, 500–502 (2007). ArticleCASPubMed Google Scholar
Harrington, E. A. et al. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nature Med.10, 262–267 (2004). ArticleCASPubMed Google Scholar
O'Hare, T. et al. Inhibition of T315I BCR–ABL and other imatinib-resistant BCR–ABL mutants by the selective ABL kinase inhibitor SGX70393. Blood108, Abstract 1373 (2006). Article Google Scholar
Shakespeare, W. et al. Orally active inhibitors of the imatinib resistant BCR–ABL mutant T315I. Blood108, Abstract 2180 (2006).
White, D. L. et al. OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood108, 697–704 (2006). ArticleCASPubMed Google Scholar
White, D. et al. In vitro sensitivity to imatinib-induced inhibition of ABL kinase activity is predictive of molecular response in patients with de novo CML. Blood106, 2520–2526 (2005). ArticleCASPubMed Google Scholar
Danhauser-Riedl, S., Warmuth, M., Druker, B. J., Emmerich, B. & Hallek, M. Activation of Src kinases p53/56lyn and p59hck by p210bcr/abl in myeloid cells. Cancer Res.56, 3589–3596 (1996). CASPubMed Google Scholar
Donato, N. J. et al. BCR–ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood101, 690–698 (2003). ArticleCASPubMed Google Scholar
Wilson, M. B., Schreiner, S. J., Choi, H. J., Kamens, J. & Smithgall, T. E. Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr–Abl signal transduction and oncogenesis. Oncogene21, 8075–8088 (2002). ArticleCASPubMed Google Scholar
Jordanides, N. E., Jorgensen, H. G., Holyoake, T. L. & Mountford, J. C. Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate. Blood108, 1370–1373 (2006). ArticleCASPubMed Google Scholar
Bao, S. et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature444, 756–760 (2006). ArticleCASPubMed Google Scholar
Radich, J. P. et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc. Natl Acad. Sci. USA (2006). An important recent microarray analysis of the genes upregulated in different phases of CML, which highlights the presence of variable genetic signatures in different phases of the disease.
Roeder, I. et al. Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implications. Nature Med.12, 1181–1184 (2006). ArticleCASPubMed Google Scholar
Weinstein, I. B. et al. Disorders in cell circuitry associated with multistage carcinogenesis: exploitable targets for cancer prevention and therapy. Clin. Cancer Res.3, 2696–2702 (1997). CASPubMed Google Scholar
Weinstein, I. B. Cancer. Addiction to oncogenes — the Achilles heal of cancer. Science297, 63–64 (2002). ArticleCASPubMed Google Scholar
Sharma, S. V., Fischbach, M. A., Haber, D. A. & Settleman, J. “Oncogenic shock”: explaining oncogene addiction through differential signal attenuation. Clin. Cancer Res.12, 4392s–4395s (2006). ArticleCASPubMed Google Scholar
Sharma, S. V. et al. A common signaling cascade may underlie “addiction” to the Src, BCR–ABL, and EGF receptor oncogenes. Cancer Cell10, 425–435 (2006). ArticleCASPubMedPubMed Central Google Scholar
Chu, S., Holtz, M., Gupta, M. & Bhatia, R. BCR/ABL kinase inhibition by imatinib mesylate enhances MAP kinase activity in chronic myelogenous leukemia CD34+ cells. Blood103, 3167–3174 (2004). ArticleCASPubMed Google Scholar
Deacon, K., Mistry, P., Chernoff, J., Blank, J. L. & Patel, R. p38 mitogen-activated protein kinase mediates cell death and p21-activated kinase mediates cell survival during chemotherapeutic drug-induced mitotic arrest. Mol. Biol. Cell14, 2071–2087 (2003). ArticleCASPubMedPubMed Central Google Scholar
Losa, J. H. et al. Role of the p38 MAPK pathway in cisplatin-based therapy. Oncogene22, 3998–4006 (2003). ArticleCAS Google Scholar
Puri, P. L. et al. Induction of terminal differentiation by constitutive activation of p38 MAP kinase in human rhabdomyosarcoma cells. Genes Dev.14, 574–584 (2000). ArticleCASPubMedPubMed Central Google Scholar
Lahaye, T. et al. Response and resistance in 300 patients with BCR–ABL-positive leukemias treated with imatinib in a single center: a 4.5-year follow-up. Cancer103, 1659–1669 (2005). ArticlePubMed Google Scholar
Lange, T., Park, B., Willis, S. G. & Deininger, M. W. BCR–ABL kinase domain mutations in chronic myeloid leukemia: not quite enough to cause resistance to imatinib therapy? Cell Cycle4, 1761–1766 (2005). ArticleCASPubMed Google Scholar
Corey, S. J. et al. Requirement of Src kinase Lyn for induction of DNA synthesis by granulocyte colony-stimulating factor. J. Biol. Chem.273, 3230–3235 (1998). ArticleCASPubMed Google Scholar
Donato, N. J. et al. Imatinib mesylate resistance through BCR–ABL independence in chronic myelogenous leukemia. Cancer Res.64, 672–677 (2004). ArticleCASPubMed Google Scholar
Tipping, A. J., Deininger, M. W., Goldman, J. M. & Melo, J. V. Comparative gene expression profile of chronic myeloid leukemia cells innately resistant to imatinib mesylate. Exp. Hematol.31, 1073–1080 (2003). ArticleCASPubMed Google Scholar
Walkley, C. R. et al. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor γ deficiency. Cell129, 1097–1110 (2007). ArticleCASPubMedPubMed Central Google Scholar
Walkley, C. R., Shea, J. M., Sims, N. A., Purton, L. E. & Orkin, S. H. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell129, 1081–1095 (2007). ArticleCASPubMedPubMed Central Google Scholar
Krause, D. S., Lazarides, K., von Andrian, U. H. & Van Etten, R. A. Requirement for CD44 in homing and engraftment of BCR–ABL-expressing leukemic stem cells. Nature Med.12, 1175–1180 (2006). ArticleCASPubMed Google Scholar
Rossi, D. J. et al.Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature447, 725–729 (2007). ArticleCASPubMed Google Scholar
Krivtsov, A. V. et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9. Nature442, 818–822 (2006). Kristovet al. illustrated the capacity to recapitulate stem cell features in progeny cells by viral transfection of a powerful oncogene. ArticleCASPubMed Google Scholar
Huntly, B. J. et al. MOZ–TIF2, but not BCR–ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell6, 587–596 (2004). ArticleCASPubMed Google Scholar
Cozzio, A. et al. Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev.17, 3029–3035 (2003). ArticleCASPubMedPubMed Central Google Scholar
So, C. W. et al. MLL–GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell3, 161–171 (2003). ArticleCASPubMed Google Scholar
Marley, S. B., Deininger, M. W., Davidson, R. J., Goldman, J. M. & Gordon, M. Y. The tyrosine kinase inhibitor STI571, like interferon-α, preferentially reduces the capacity for amplification of granulocyte-macrophage progenitors from patients with chronic myeloid leukemia. Exp. Hematol.28, 551–557 (2000). ArticleCASPubMed Google Scholar
Gordon, M. Y. et al. Treatment with interferon-α preferentially reduces the capacity for amplification of granulocyte-macrophage progenitors (CFU-GM) from patients with chronic myeloid leukemia but spares normal CFU-GM. J. Clin. Invest.102, 710–715 (1998). ArticleCASPubMedPubMed Central Google Scholar
Somervaille, T. C. & Cleary, M. L. Identification and characterization of leukemia stem cells in murine MLL–AF9 acute myeloid leukemia. Cancer Cell10, 257–268 (2006). ArticleCASPubMed Google Scholar
Arce, L., Yokoyama, N. N. & Waterman, M. L. Diversity of LEF/TCF action in development and disease. Oncogene25, 7492–7504 (2006). ArticleCASPubMed Google Scholar
Scheller, M. et al. Hematopoietic stem cell and multilineage defects generated by constitutive β-catenin activation. Nature Immunol.7, 1037–1047 (2006). ArticleCAS Google Scholar
Kirstetter, P., Anderson, K., Porse, B. T., Jacobsen, S. E. & Nerlov, C. Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nature Immunol.7, 1048–1056 (2006). ArticleCAS Google Scholar
Lawson, N. D. et al. Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development128, 3675–3683 (2001). ArticleCASPubMed Google Scholar
Maillard, I., He, Y. & Pear, W. S. From the yolk sac to the spleen: New roles for Notch in regulating hematopoiesis. Immunity18, 587–589 (2003). ArticleCASPubMed Google Scholar
Pui, J. C. et al. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity11, 299–308 (1999). ArticleCASPubMed Google Scholar
Ellisen, L. W. et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell66, 649–661 (1991). ArticleCASPubMed Google Scholar
Park, I. K. et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature423, 302–305 (2003). ArticleCASPubMed Google Scholar
Sauvageau, G. et al. Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. Proc. Natl Acad. Sci. USA91, 12223–12227 (1994). ArticleCASPubMedPubMed Central Google Scholar
Hess, J. L., Yu, B. D., Li, B., Hanson, R. & Korsmeyer, S. J. Defects in yolk sac hematopoiesis in _Mll_-null embryos. Blood90, 1799–1806 (1997). ArticleCASPubMed Google Scholar
Ernst, P. et al. Definitive hematopoiesis requires the mixed-lineage leukemia gene. Dev. Cell6, 437–443 (2004). ArticleCASPubMed Google Scholar
Steidl, U. et al. Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Nature Genet.38, 1269–1277 (2006). ArticleCASPubMed Google Scholar
Lessard, J. & Sauvageau, G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature423, 255–260 (2003). ArticleCASPubMed Google Scholar
Mansour, M. R., Linch, D. C., Foroni, L., Goldstone, A. H. & Gale, R. E. High incidence of Notch-1 mutations in adult patients with T-cell acute lymphoblastic leukemia. Leukemia20, 537–539 (2006). ArticleCASPubMed Google Scholar
Tohda, S., Kogoshi, H., Murakami, N., Sakano, S. & Nara, N. Diverse effects of the Notch ligands Jagged1 and Delta1 on the growth and differentiation of primary acute myeloblastic leukemia cells. Exp. Hematol.33, 558–563 (2005). ArticleCASPubMed Google Scholar
Sengupta, A. et al. Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression. Leukemia21, 949–955 (2007). ArticleCASPubMed Google Scholar
Aguirre-Ghiso, J. A., Ossowski, L. & Rosenbaum, S. K. Green fluorescent protein tagging of extracellular signal-regulated kinase and p38 pathways reveals novel dynamics of pathway activation during primary and metastatic growth. Cancer Res.64, 7336–7345 (2004). ArticleCASPubMed Google Scholar
Pruitt, K., Pruitt, W. M., Bilter, G. K., Westwick, J. K. & Der, C. J. Raf-independent deregulation of p38 and JNK mitogen-activated protein kinases are critical for Ras transformation. J. Biol. Chem.277, 31808–31817 (2002). ArticleCASPubMed Google Scholar
Molofsky, A. V. et al. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature425, 962–967 (2003). ArticleCASPubMedPubMed Central Google Scholar
Voncken, J. W. et al. MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1. J. Biol. Chem.280, 5178–5187 (2005). ArticleCASPubMed Google Scholar
Mohty, M., Yong, A. S., Szydlo, R. M., Apperley, J. F. & Melo, J. V. The polycomb group BMI-1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia. Blood110, 380–383 (2007). ArticleCASPubMed Google Scholar
Melo, J. V. & Barnes, D. J. Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nature Rev. Cancer7, 441–453 (2007). ArticleCAS Google Scholar
Angstreich, G. R. et al. Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitors. Br. J. Haematol.130, 373–381 (2005). ArticleCASPubMed Google Scholar
Talpaz, M. et al. Persistence of dormant leukemic progenitors during interferon-induced remission in chronic myelogenous leukemia. Analysis by polymerase chain reaction of individual colonies. J. Clin. Invest.94, 1383–1389 (1994). A PCR analysis illustrating the presence of dormant leukaemic progenitors in an interferon-α -induced remission, and thereby suggesting a role of induced immunosurvellience, rather than eradication of CML, with interferon-α therapy. ArticleCASPubMedPubMed Central Google Scholar
Rousselot, P. et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood109, 58–60 (2007). Use of imatinib after previous interferon-α treatment resulted in long-term responses without any type of maintenance therapy. This raised the question of potentially reevaluating the use of interferon-α in modern treatment of CML. ArticleCASPubMed Google Scholar