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Concepts of human leukemic development

Oncogene volume 23, pages 7164–7177 (2004)Cite this article

Abstract

Two fundamental problems in cancer research are identification of the normal cell within which cancer initiates and identification of the cell type capable of sustaining the growth of the neoplastic clone. There is overwhelming evidence that virtually all cancers are clonal and represent the progeny of a single cell. What is less clear for most cancers is which cells within the tumor clone possess tumorigenic or ‘cancer stem cell’ (CSC) properties and are capable of maintaining tumor growth. The concept that only a subpopulation of rare CSC is responsible for maintenance of the neoplasm emerged nearly 50 years ago. Testing of this hypothesis is most advanced for the hematopoietic system due to the establishment of functional in vitro and in vivo assays for stem and progenitor cells at all stages of development. This body of work led to conclusive proof for CSC with the identification and purification of leukemic stem cells capable of repopulating NOD/SCID mice. This review will focus on the historical development of the CSC hypothesis, the mechanisms necessary to subvert normal developmental programs, and the identification of the cell in which these leukemogenic events first occur.

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References

  • Abu-Duhier FM, Goodeve AC, Wilson GA, Care RS, Peake IR and Reilly JT . (2001). Br. J. Haematol., 113, 983–988.

  • Adya N, Stacy T, Speck NA and Liu PP . (1998). Mol. Cell. Biol., 18, 7432–7443.

  • Ailles LE, Gerhard B, Kawagoe H and Hogge DE . (1999). Blood, 94, 1761–1772.

  • Al-Hajj M, Wicha M, Morrison SJ and Clarke MF . (2003). Proc. Natl. Acad. Sci. USA, 100, 3983–3988.

  • Albitar M, Manshouri T, Shen Y, Liu D, Beran M, Kantarjian HM, Rogers A, Jilani I, Lin CW, Pierce S, Freireich EJ and Estey EH . (2002). Blood, 100, 791–798.

  • Becker AJ, McCulloch EA and Till JE . (1963). Nature, 197, 452–454.

  • Beghini A, Peterlongo P, Ripamonti CB, Larizza L, Cairoli R, Morra E and Mecucci C . (2000). Blood, 95, 726–727.

  • Bennett J, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR and Sultan C . (1976). Br. J. Haematol., 33, 451–458.

  • Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR and Sultan C . (1985). Ann. Intern. Med., 103, 460–462.

  • Bernstein ID, Singer JW, Smith FO, Andrews RG, Flowers DA, Petersens J, Steinmann L, Najfeld V, Savage D, Fruchtman S, Arlin Z and Fialkow PJ . (1992). Blood, 79, 1811–1816.

  • Bhatia M, Bonnet D, Murdoch B, Gan OI and Dick JE . (1998). Nat. Med., 4, 1038–1045.

  • Birg F, Courcoul M, Rosnet O, Bardin F, Pebusque MJ, Marchetto S, Tabilio A, Mannoni P and Birnbaum D . (1992). Blood, 80, 2584–2593.

  • Blackstock AM and Garson OM . (1974). Lancet, 2, 1178–1179.

  • Blair A, Hogge DE, Ailles LE, Lansdorp PM and Sutherland HJ . (1997). Blood, 89, 3104–3112.

  • Blair A, Hogge DE and Sutherland HJ . (1998). Blood, 92, 4325–4335.

  • Blair A and Sutherland HJ . (2000). Exp. Hematol., 28, 660–671.

  • Bonnet D . (2001). Rev. Clin. Exp. Hematol., 5, 42–61.

  • Bonnet D and Dick JE . (1997). Nat. Med., 3, 730–737.

  • Bradley TR and Metcalf D . (1966). Aust. J. Exp. Biol. Med. Sci., 44, 287–299.

  • Brendel C, Mohr B, Schimmelpfennig C, Muller J, Bornhauser M, Schmidt M, Ritter M, Ehninger G and Neubauer A . (1999). Leukemia, 13, 1770–1775.

  • Britos-Bray M, Ramirez M, Cao W, Wang X, Liu PP, Civin CI and Friedman AD . (1998). Blood, 92, 4344–4352.

  • Broccoli D, Young JW and de Lange T . (1995). Proc. Natl. Acad. Sci. USA, 92, 9082–9086.

  • Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG, Atwater S and Bishop JM . (1997). Proc. Natl. Acad. Sci. USA, 94, 2551–2556.

  • Bruce WR and Van Der Gaag H . (1963). Nature, 199, 79–80.

  • Budel LM, Touw IP, Delwel R, Clark SC and Lowenberg B . (1989). Blood, 74, 565–571.

  • Buick RN and MacKillop WJ . (1981). Br. J. Cancer, 44, 349–355.

  • Buick RN, Minden MD and McCulloch EA . (1979). Blood, 54, 95–104.

  • Buick RN and Pollak MN . (1984). Cancer Res., 44, 4909–4918.

  • Busque L, Mio R, Mattioli J, Brais E, Blais N, Lalonde Y, Maragh M and Gilliland DG . (1996). Blood, 88, 59–65.

  • Campos L, Rouault JP, Sabido O, Oriol P, Roubi N, Vasselon C, Archimbaud E, Magaud JP and Guyotat D . (1993). Blood, 81, 3091–3096.

  • Carow CE, Levenstein M, Kaufmann SH, Chen J, Amin S, Rockwell P, Witte L, Borowitz MJ, Civin CI and Small D . (1996). Blood, 87, 1089–1096.

  • Cashman J, Bockhold K, Hogge DE, Eaves AC and Eaves CJ . (1997). Br. J. Haematol., 98, 1026–1036.

  • Castilla LH, Garrett L, Adya N, Orlic D, Dutra A, Anderson S, Owens J, Eckhaus M, Bodine D and Liu PP . (1999). Nat. Genet., 23, 144–146.

  • Clarkson B, Fried J, Strife A, Sakai Y, Ota K and Okita T . (1970). Cancer, 25, 1237–1260.

  • Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML and Weissman IL . (2003). Genes Dev., 17, 3029–3035.

  • Dash A and Gilliland DG . (2001). Best Pract. Res. Clin. Haematol., 14, 49–64.

  • Davis RE and Greenberg PL . (1998). Leuk. Res., 22, 767–777.

  • Dehmel U, Zaborski M, Meierhoff G, Rosnet O, Birnbaum D, Ludwig WD, Quentmeier H and Drexler HG . (1996). Leukemia, 10, 261–270.

  • Dick JE . (2003a). Proc. Natl. Acad. Sci. USA, 100, 3547–3549.

  • Dick JE . (2003b). Nature, 423, 231–233.

  • Drexler HG, Meyer C and Quentmeier H . (1999). Leuk. Lymphoma, 33, 83–91.

  • Edwards RH, Wasik MA, Finan J, Rodriguez R, Moore J, Kamoun M, Rennert H, Bird J, Nowell PC and Salhany KE . (1999). Am. J. Clin. Pathol., 112, 819–827.

  • Engelhardt M, Kumar R, Albanell J, Pettengell R, Han W and Moore MA . (1997). Blood, 90, 182–193.

  • Enver T and Greaves M . (1998). Cell, 94, 9–12.

  • Ferraris AM, Raskind WH, Bjornson BH, Jacobson RJ, Singer JW and Fialkow PJ . (1985). Blood, 66, 342.

  • Ferrucci PF, Grignani F, Pearson M, Fagioli M, Nicoletti I and Pelicci PG . (1997). Proc. Natl. Acad. Sci. USA, 94, 10901–10906.

  • Fialkow P, Singer J, Raskind W, Adamson J, Jacobson R, Bernstein I, Najfeld V and Veith R . (1987a). N. Engl. J. Med., 317, 468–473.

  • Fialkow PJ, Singer JW, Adamson JW, Vaidya K, Dow LW, Ochs J and Moohr JW . (1981). Blood, 57, 1068–1073.

  • Fialkow PJ, Singer JW, Raskind WH, Adamson JW, Jacobson RJ, Bernstein ID, Dow LW, Najfeld V and Veith R . (1987b). N. Engl. J. Med., 317, 468–473.

  • Gale RE, Fielding AK, Harrison CN and Linch DC . (1997). Br. J. Haematol., 98, 512–519.

  • Gale RE and Linch DC . (1998). Leukemia, 12, 117–120.

  • Gari M, Goodeve A, Wilson G, Winship P, Langabeer S, Linch D, Vandenberghe E, Peake I and Reilly J . (1999). Br. J. Haematol., 105, 894–900.

  • Gelmetti V, Zhang J, Fanelli M, Minucci S, Pelicci PG and Lazar MA . (1998). Mol. Cell. Biol., 18, 7185–7191.

  • Gilliland DG and Tallman MS . (2002). Cancer Cell, 1, 417–420.

  • Greaves MF, Chan LC, Furley AJW, Watt SM and Molgaard HV . (1986). Blood, 67, 1–11.

  • Griffin J and Löwenberg B . (1986). Blood, 68, 1185–1195.

  • Grignani F, Ferrucci PF, Testa U, Talamo G, Fagioli M, Alcalay M, Mencarelli A, Peschle C, Nicoletti I and Pelicci PG . (1993). Cell, 74, 423–431.

  • Grignani F, Valtieri M, Gabbianelli M, Gelmetti V, Botta R, Luchetti L, Masella B, Morsilli O, Pelosi E, Samoggia P, Pelicci PG and Peschle C . (2000). Blood, 96, 1531–1537.

  • Grimwade D and Enver T . (2004). Leukemia, 18, 375–384.

  • Grimwade D, Outram SV, Flora R, Ings SJ, Pizzey AR, Morilla R, Craddock CF, Linch DC and Solomon E . (2002). Cancer Res., 62, 4730–4735.

  • Grisolano JL, Wesselschmidt RL, Pelicci PG and Ley TJ . (1997). Blood, 89, 376–387.

  • Guan Y and Hogge DE . (2000). Leukemia, 14, 2135–2141.

  • Guenechea G, Gan OI, Inamitsu T, Dorrell C, Pereira DS, Kelly M, Naldini L and Dick JE . (2000). Mol. Ther., 1, 566–573.

  • Guthridge MA, Barry EF, Felquer FA, McClure BJ, Stomski FC, Ramshaw H and Lopez AF . (2004). Blood, 103, 820–827.

  • Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA, Luger SM and Jordan CT . (2001). Blood, 98, 2301–2307.

  • Haase D, Feuring-Buske M, Konemann S, Fonatsch C, Troff C, Verbeek W, Pekrun A, Hiddemann W and Wormann B . (1995). Blood, 86, 2906–2912.

  • Hamburger AW and Salmon SE . (1977). Science, 197, 461–463.

  • Hanahan D and Weinberg RA . (2000). Cell, 100, 57–70.

  • Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA and Bloomfield CD . (1999). J. Clin. Oncol., 17, 3835–3849.

  • Haughn L, Hawley RG, Morrison DK, von Boehmer H and Hockenbery DM . (2003). J. Biol. Chem., 278, 25158–25165.

  • Hayflick L . (1997). Biochemistry (Mosc), 62, 1180–1190.

  • He LZ, Tribioli C, Rivi R, Peruzzi D, Pelicci PG, Soares V, Cattoretti G and Pandolfi PP . (1997). Proc. Natl. Acad. Sci. USA, 94, 5302–5307.

  • Hemann MT, Strong MA, Hao LY and Greider CW . (2001). Cell, 107, 67–77.

  • Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M and Kornblum HI . (2003). Proc. Natl. Acad. Sci. USA, 100, 15178–15183.

  • Heppner GH . (1984). Cancer Res., 44, 2259–2265.

  • Higuchi M, O'Brien D, Kumaravelu P, Lenny N, Yeoh EJ and Downing JR . (2002). Cancer Cell, 1, 63–74.

  • Hope K, Jin L and Dick JE . (2004). Nat. Immunol. Epub 2004 May 30.

  • Ichikawa Y, Paran M and Sachs L . (1969). J. Cell. Physiol., 73, 43–47.

  • Ikeda H, Kanakura Y, Tamaki T, Kuriu A, Kitayama H, Ishikawa J, Kanayama Y, Yonezama T, Tarui S and Griffin J . (1991). Blood, 78, 2962.

  • Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL, Meyerrose T, Rossi R, Grimes B, Rizzieri DA, Luger SM and Phillips GL . (2000). Leukemia, 14, 1777–1784.

  • Kakizuka A, Miller WH, Jr, Umesono K, Warrell Jr RP, Frankel SR, Murty VV, Dmitrovsky E and Evans RM . (1991). Cell, 66, 663–674.

  • Keinänen M, Griffin J, Bloomfield C, Machnicki J and de la Chapelle A . (1988). N. Engl. J. Med., 318, 1153–1158.

  • Kogan SC, Brown DE, Shultz DB, Truong BTH, Lallemand-Breitenbach V, Guillemin MC, Lagasse E, Weissman IL and Bishop JM . (2001). J. Exp. Med., 193, 531–543.

  • Konopleva M, Tari AM, Estrov Z, Harris D, Xie Z, Zhao S, Lopez-Berestein G and Andreeff M . (2000). Blood, 95, 3929–3938.

  • Korn AP, Helkelman RM, Ottensmeyer EP and Till JE . (1973). Exp. Hematol., 1, 362–375.

  • Kraemer PM, Ray FA, Brothman AR, Bartholdi MF and Cram LS . (1986). J. Natl. Cancer Inst., 76, 703–709.

  • Kroon E, Krosl J, Thorsteinsdottir U, Baban S, Buchberg A and Sauvageau G . (1998). EMBO J., 17, 3714–3725.

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA and Dick JE . (1994). Nature, 367, 645–648.

  • Lessard J, Baban S and Sauvageau G . (1998). Blood, 91, 1216–1224.

  • Lessard J and Sauvageau G . (2003). Nature, 423, 455–460.

  • Liu P, Tarle SA, Hajra A, Claxton DF, Marlton P, Freedman M, Siciliano MJ and Collins FS . (1993). Science, 261, 1041–1044.

  • Liu Y, Kha H, Ungrin M, Robinson MO and Harrington L . (2002). Proc. Natl. Acad. Sci. USA, 99, 3597–3602.

  • Lutterbach B, Hou Y, Durst KL and Hiebert SW . (1999). Proc. Natl. Acad. Sci. USA, 96, 12822–12827.

  • Lutterbach B, Westendorf JJ, Linggi B, Patten A, Moniwa M, Davie JR, Huynh KD, Bardwell VJ, Lavinsky RM, Rosenfeld MG, Glass C, Seto E and Hiebert SW . (1998). Mol. Cell. Biol., 18, 7176–7184.

  • Lyman SD and Jacobsen SE . (1998). Blood, 91, 1101–1134.

  • Mackillop WJ, Ciampi A, Till JE and Buick RN . (1983). J. Natl. Cancer Inst., 70, 9–16.

  • Matas D, Milyavsky M, Shats I, Nissim L, Goldfinger N and Rotter V . (2004). Cell Death Differ., 4, 458–467.

  • McCulloch E . (1983). Blood, 62, 1–13.

  • McCulloch EA, Howatson AF, Buick RN, Minden MD and Izaguirre CA . (1979). Blood Cells, 5, 261–282.

  • Mehrotra B, George TI, Kavanau K, Avet-Loiseau H, Moore II D, Willman CL, Slovak ML, Atwater S, Head DR and Pallavicini MG . (1995). Blood, 86, 1139–1147.

  • Mendelsohn ML . (1962). Science, 135, 213–215.

  • Metcalf D . (1973). Br. J. Cancer, 27, 191–202.

  • Metcalf D, Moore MA and Warner NL . (1969). J. Natl. Cancer Inst., 43, 983–1001.

  • Meyers S, Lenny N and Hiebert SW . (1995). Mol. Cell. Biol., 15, 1974–1982.

  • Miller Jr WH and Waxman S . (2002). Oncogene, 21, 3496–3506.

  • Minden MD, Buick RN and McCulloch EA . (1979). Blood, 54, 186–195.

  • Miyamoto T, Nagafuji K, Akashi K, Harada M, Kyo T, Akashi T, Takenaka K, Mizuno S, Gondo H, Okamura T, Dohy H and Niho Y . (1996). Blood, 87, 4789–4796.

  • Miyamoto T, Weissman IL and Akashi K . (2000). Proc. Natl. Acad. Sci. USA, 97, 7521–7526.

  • Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF and Morrison SJ . (2003). Nature, 425, 962–967.

  • Moore M, Williams N and Metcalfe D . (1974). J. Natl. Cancer Inst., 50, 603.

  • Mulloy JC, Cammenga J, Berguido FJ, Wu K, Zhou P, Comenzo RL, Jhanwar S, Moore MA and Nimer SD . (2003). Blood, 102, 4369–4376.

  • Nakao M, Yokota S, Iwai T, Kaneko H, Horiike S, Kashima K, Sonoda Y, Fujimoto T and Misawa S . (1996). Leukemia, 10, 1911–1918.

  • Nara N and McCulloch EA . (1985). Blood, 65, 1484–1493.

  • Ohyashiki JH, Sashida G, Tauchi T and Ohyashiki K . (2002). Oncogene, 21, 680–687.

  • Osato M, Asou N, Abdalla E, Hoshino K, Yamasaki H, Okubo T, Suzushima H, Takatsuki K, Kanno T, Shigesada K and Ito Y . (1999). Blood, 93, 1817–1824.

  • Pandolfi PP . (2001). Oncogene, 20, 3116–3127.

  • Park IK, He Y, Lin F, Laerum OD, Tian Q, Bumgarner R, Klug CA, Li K, Kuhr C, Doyle MJ, Xie T, Schummer M, Sun Y, Goldsmith A, Clarke MF, Weissman IL, Hood L and Li L . (2002). Blood, 99, 488–498.

  • Park IK, Qian D, Kiel M, Becker M, Pihalja M, Weissman IL, Morrison SJ and Clarke M . (2003). Nature, 423, 302–305.

  • Pereira DS, Dorrell C, Ito CY, Gan OI, Murdoch B, Rao VN, Zou JP, Reddy ES and Dick JE . (1998). Proc. Natl. Acad. Sci. USA, 95, 8239–8244.

  • Pluznik DH and Sachs L . (1965). J. Cell. Physiol., 66, 319–324.

  • Preudhomme C, Warot-Loze D, Roumier C, Grardel-Duflos N, Garand R, Lai JL, Dastugue N, Macintyre E, Denis C, Bauters F, Kerckaert JP, Cosson A and Fenaux P . (2000). Blood, 96, 2862–2869.

  • Raymakers R, Wittebol S, Pennings A, Linders E, Poddighe P and De Witte T . (1995). Leukemia, 9, 450–457.

  • Reilly JT . (2003). Blood Rev., 17, 241–248.

  • Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R and Weissman IL . (2003). Nature, 423, 409–414.

  • Reya T, Morrison SJ, Clarke MF and Weissman IL . (2001). Nature, 414, 105–111.

  • Rufer N, Brummendorf TH, Chapuis B, Helg C, Lansdorp PM and Roosnek E . (2001). Blood, 97, 575–577.

  • Rufer N, Brummendorf TH, Kolvraa S, Bischoff C, Christensen K, Wadsworth L, Schulzer M and Lansdorp PM . (1999). J. Exp. Med., 190, 157–167.

  • Sauvageau G, Thorsteinsdottir U, Eaves CJ, Lawrence HJ, Largman C, Lansdorp PM and Humphries RK . (1995). Genes Dev., 9, 1753–1765.

  • Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, Loffler H, Sauerland CM, Serve H, Buchner T, Haferlach T and Hiddemann W . (2002). Blood, 100, 59–66.

  • Schwieger M, Lohler J, Fischer M, Herwig U, Tenen DG and Stocking C . (2004). Blood, 103, 2744–2752.

  • Shay JW and Wright WE . (1989). Exp. Cell Res., 184, 109–118.

  • Singh S, Clarke I, Terasaki M, Bonn V, Hawkins C, Squire J and Dirks P . (2003). Cancer Res., 63, 5281–5288.

  • So CW, Karsunky H, Passegue E, Cozzio A, Weissman IL and Cleary ML . (2003). Cancer cell, 3, 161–171.

  • Southam C and Brunschwig A . (1960). Cancer, 14, 971–978.

  • Speck NA and Gilliland DG . (2002). Nat. Rev. Cancer, 2, 502–513.

  • Sutherland HJ, Blair A and Zapf RW . (1996). Blood, 87, 4754–4761.

  • Tenen DG . (2003). Nat. Rev. Cancer, 3, 89–101.

  • Terpstra W, Ploemacher RE, Prins A, van Lom K, Pouwels K, Wognum AW, Wagemaker G, Lowenberg B and Wielenga JJ . (1996a). Blood, 88, 1944–1950.

  • Terpstra W, Prins A, Ploemacher RE, Wognum BW, Wagemaker G, Lowenberg B and Wielenga JJ . (1996b). Blood, 87, 2187–2194.

  • Testa U, Grignani F, Samoggia P, Zanetti C, Riccioni R, Lo Coco F, Diverio D, Felli N, Passerini CG, Grell M, Pelicci PG and Peschle C . (1998). J. Clin. Invest., 101, 2278–2289.

  • Testa U, Riccioni R, Diverio D, Rossini A, Lo Coco F and Peschle C . (2004). Leukemia, 18, 219–226.

  • Testa U, Riccioni R, Militi S, Coccia E, Stellacci E, Samoggia P, Latagliata R, Mariani G, Rossini A, Battistini A, Lo-Coco F and Peschle C . (2002). Blood, 100, 2980–2988.

  • Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U, Wermke M, Bornhauser M, Ritter M, Neubauer A, Ehninger G and Illmer T . (2002). Blood, 99, 4326–4335.

  • Thorsteinsdottir U, Sauvageau G and Humphries RK . (1997). Hematol. Oncol. Clin. N Am., 11, 1221–1237.

  • Till JE and McCulloch EA . (1961). Radiat Res., 14, 213–222.

  • Till JE, McCulloch EA and Siminovitch L . (1964). Proc. Natl. Acad Sci. USA, 51, 29–36.

  • Turhan AG, Lemoine FM, Debert C, Bonnet ML, Baillou C, Picard F, Macintyre EA and Varet B . (1995). Blood, 85, 2154–2161.

  • Wang JM, Lai MZ and Yang-Yen HF . (2003). Mol. Cell. Biol., 23, 1896–1909.

  • Wantzin GL and Killmann SA . (1977). Eur. J. Cancer., 13, 647–655.

  • Wright WE and Shay JW . (2000). Nat. Med., 6, 849–851.

  • Yamamoto Y, Kiyoi H, Nakano Y, Suzuki R, Kodera Y, Miyawaki S, Asou N, Kuriyama K, Yagasaki F, Shimazaki C, Akiyama H, Saito K, Nishimura M, Motoji T, Shinagawa K, Takeshita A, Saito H, Ueda R, Ohno R and Naoe T . (2001). Blood, 97, 2434–2439.

  • Yokota S, Kiyoi H, Nakao M, Iwai T, Misawa S, Okuda T, Sonoda Y, Abe T, Kahsima K, Matsuo Y and Naoe T . (1997). Leukemia, 11, 1605–1609.

  • Yui J, Chiu CP and Lansdorp PM . (1998). Blood, 91, 3255–3262.

  • Zanjani E, Almeida-Porada G, Livingston AG, Flake AW and Ogawa M . (1998). Exp. Hematol., 26, 353–360.

  • Zheng R, Levis M, Piloto O, Brown P, Baldwin BR, Gorin NC, Beran M, Zhu Z, Ludwig D, Hicklin D, Witte L, Li Y and Small D . (2004). Blood, 103, 267–274.

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Acknowledgements

This work was supported by the National Cancer Institute of Canada (NCIC) with funds from the Canadian Cancer Society, Canadian Institutes for Health Research, Stem Cell Network of the National Centres of Excellence, Canadian Genetic Diseases Network of the National Centres of Excellence, and a Canada Research Chair.

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    Jennifer K Warner, Jean C Y Wang, Kristin J Hope, Liqing Jin & John E Dick

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Warner, J., Wang, J., Hope, K. et al. Concepts of human leukemic development. Oncogene 23, 7164–7177 (2004). https://doi.org/10.1038/sj.onc.1207933

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