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Mechanisms underlying abnormal trafficking and expansion of malignant progenitors in CML: BCR/ABL-induced defects in integrin function in CML

Oncogene volume 21, pages 8605–8611 (2002)Cite this article

Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell characterized by the presence of the Philadelphia chromosome (Ph) (Nowell and Hungerford, 1960) and the formation of the BCR/ABL fusion gene (Rowley, 1973), encoding the p210BCR/ABL oncoprotein. Clinically, CML is characterized by the premature circulation of a massively expanded immature myeloid progenitor and precursor pool in the blood. At the cellular level, CML is characterized by an increased proliferation, increased resistance to apoptosis and alterations in adhesion properties of leukemic progenitors. This review will discuss studies by others and our group over the last 10 years that evaluated mechanisms underlying abnormal trafficking and expansion of malignant progenitors in chronic myelogenous leukemia due to abnormal progenitor/microenvironment interactions in CML as a result of the oncoprotein. We will also discuss what is known to date regarding the molecular mechanisms underlying abnormal integrin function in CML.

Other investigators have also shown abnormalities in the adhesive behavior of p210BCR/ABL containing cells. Most studies were done using BCR/ABL containing cell lines. Bazzoni et al. (1996) showed that BCL/ABL-transfected GM-CSF or IL-3 dependent human (MO7e) and mouse (32D, Baf/3) hematopoietic cell lines adhere better to FN than mock-transfected cells. This effect was due to enhanced function of the VLA-5 integrin receptors and not to increased surface expression. Kramer et al. (1999) showed that expression of p21BCR-ABL in 32D cells upregulates levels of α5β1 integrins, and induces adhesion to FN. Recently, Wertheim et al. (2002) confirmed that p210BCR-ABL mediates increased adhesion of 32D cells to FN, but as was reported by Bazzoni et al. (1996) that changes in adhesion are independent of change in α5β1 and α4β1 integrins expression (Wertheim et al., 2002). Furthermore, they found that the increased adhesion was independent of p210BCR-ABL tyrosine kinase activity. Bazzoni et al. (1996) also evaluated the adhesion of CML CD34+ cells to FN and found that hematopoietic progenitors cells from CML patients have increased ability to adhere to FN than NL progenitors.

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References

  • Bazzoni G, Carlesso N, Griffin JD, Hemler ME . 1996 J. Clin. Invest. 98: 521–528

  • Bhatia R, McCarthy JB, Verfaillie CM . 1996 Blood 87: 3883–3891

  • Bhatia R, McGlave PB, Verfaillie CM . 1995 J. Clin. Invest. 96: 931–939

  • Bhatia R, Munthe HA, Verfaillie CM . 1998 Leukemia 12: 1708–1717

  • Bhatia R, Munthe HA, Verfaillie CM . 1999 Exp. Hematol. 27: 1384–1396

  • Bhatia R, Verfaillie CM . 1998 Blood 91: 3414–3422

  • Bhatia R, Wayner EA, McGlave PB, Verfaillie CM . 1994 J. Clin. Invest. 94: 384–391

  • Burridge K, Fath K, Kelly T, Nuckolls G, Turner C . 1988 Annu. Rev. Cell Biol. 4: 487–525

  • Carpino N, Wisniewski D, Strife A, Marshak D, Kobayashi R, Stillman B, Clarkson B . 1997 Cell 88: 197–204

  • Cashman J, Eaves AC, Eaves CJ . 1985 Blood 66: 1002–1005

  • Catzavelos C, Bhattacharya N, Ung YC, Wilson JA, Roncari L, Sandhu C, Shaw P, Yeger H, Morava-Protzner I, Kapusta L, Franssen E, Pritchard KI, Slingerland JM . 1997 Nat. Med. 3: 227–230

  • Clark EA, Brugge JS . 1995 Science 268: 233–239

  • Eaves AC, Cashman JD, Gaboury LA, Kalousek DK, Eaves CJ . 1986 Proc. Natl. Acad. Sci. USA 83: 5306–5310

  • Gesbert F, Sellers WR, Signoretti S, Loda M, Griffin JD . 2000 J. Biol. Chem. 275: 39223–39230

  • Gordon MY, Dowding CR, Riley GP, Goldman JM, Greaves MF . 1987 Nature 328: 342–344

  • Gordon MY, Dowding CR, Riley GP, Goldman JM, Greaves MF . 1989 Curr. Top. Microbiol. Immunol. 149: 151–155

  • Gotoh A, Miyazawa K, Ohyashiki K, Tauchi T, Boswell HS, Broxmeyer HE, Toyama K . 1995 Exp. Hematol. 23: 1153–1159

  • Guinebault C, Payrastre B, Racaud-Sultan C, Mazarguil H, Breton M, Mauco G, Plantavid M, Chap H . 1995 J. Cell Biol. 129: 831–842

  • Holtschke T, Lohler J, Kanno Y, Fehr T, Giese N, Rosenbauer F, Lou J, Knobeloch KP, Gabriele L, Waring JF, Bachmann MF, Zinkernagel RM, Morse III HC, Ozato K, Horak I . 1996 Cell 87: 307–317

  • Hurley RW, McCarthy JB, Verfaillie CM . 1995 J. Clin. Invest. 96: 511–519

  • Hurley RW, McCarthy JB, Wayner EA, Verfaillie CM . 1997 Exp. Hematol. 25: 321–328

  • Jiang Y, Prosper F, Verfaillie CM . 2000a Blood 95: 846–854

  • Jiang Y, Zhao RC, Verfaillie CM . 2000b Proc. Natl. Acad. Sci. USA 97: 10538–10543

  • Jonuleit T, van der Kuip H, Miething C, Michels H, Hallek M, Duyster J, Aulitzky WE . 2000 Blood 96: 1933–1939

  • Kramer A, Horner S, Willer A, Fruehauf S, Hochhaus A, Hallek M, Hehlmann R . 1999 Proc. Natl. Acad. Sci. USA 96: 2087–2092

  • Lloyd RV, Erickson LA, Jin L, Kulig E, Qian X, Cheville JC, Scheithauer BW . 1999 Am. J. Pathol. 154: 313–323

  • Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF, Jessup JM, Pagano M . 1997 Nat. Med. 3: 231–234

  • Lundell BI, McCarthy JB, Kovach NL, Verfaillie CM . 1996 Blood 87: 2450–2458

  • Lundell BI, McCarthy JB, Kovach NL, Verfaillie CM . 1997 Leukemia 11: 822–829

  • Matulonis U, Salgia R, Okuda K, Druker B, Griffin JD . 1993 Exp. Hematol. 21: 1460–1466

  • McWhirter JR, Galasso DL, Wang JY . 1993 Mol. Cell. Biol. 13: 7587–7595

  • McWhirter JR, Wang JY . 1991 Mol. Cell. Biol. 11: 1553–1565

  • McWhirter JR, Wang JY . 1993 EMBO J. 12: 1533–1546

  • Miyamoto S, Akiyama SK, Yamada KM . 1995 Science 267: 883–885

  • Nowell P, Hungerford D . 1960 Science 132: 1497

  • Oda T, Heaney C, Hagopian JR, Okuda K, Griffin JD, Druker BJ . 1994 J. Biol. Chem. 269: 22925–22928

  • O'Toole TE, Katagiri Y, Faull RJ, Peter K, Tamura R, Quaranta V, Loftus JC, Shattil SJ, Ginsberg MH . 1994 J. Cell Biol. 124: 1047–1059

  • Polyak K, Kato JY, Solomon MJ, Sherr CJ, Massague J, Roberts JM, Koff A . 1994 Genes Dev. 8: 9–22

  • Rosenbauer F, Kallies A, Scheller M, Knobeloch KP, Rock CO, Schwieger M, Stocking C, Horak I . 2002 EMBO J. 21: 211–220

  • Rowley JD . 1973 Nature 243: 290–293

  • Salgia R, Avraham S, Pisick E, Li JL, Raja S, Greenfield EA, Sattler M, Avraham H, Griffin JD . 1996a J. Biol. Chem. 271: 31222–31226

  • Salgia R, Brunkhorst B, Pisick E, Li JL, Lo SH, Chen LB, Griffin JD . 1995a Oncogene 11: 1149–1155

  • Salgia R, Li JL, Lo SH, Brunkhorst B, Kansas GS, Sobhany ES, Sun Y, Pisick E, Hallek M, Ernst T, Tantravahi R, Chen LB, Griffin JD . 1995b J. Biol. Chem. 270: 5039–5047

  • Salgia R, Pisick E, Sattler M, Li JL, Uemura N, Wong WK, Burky SA, Hirai H, Chen LB, Griffin JD . 1996b J. Biol. Chem. 271: 25198–25203

  • Salgia R, Sattler M, Pisick E, Li JL, Griffin JD . 1996c Exp. Hematol. 24: 310–313

  • Salgia R, Uemura N, Okuda K, Li JL, Pisick E, Sattler M, de Jong R, Druker B, Heisterkamp N, Groffen J, Griffen JD, Chen LB . 1995c J. Biol. Chem. 270: 29145–29150

  • Sattler M, Pride YB, Quinnan LR, Verma S, Malouf NA, Husson H, Salgia R, Lipkowitz S, Griffin JD . 2002 Oncogene 21: 1423–1433

  • Sattler M, Salgia R . 1998 Leukemia 12: 637–644

  • Schwartz MA, Schaller MD, Ginsberg MH . 1995 Annu. Rev. Cell. Dev. Biol. 11: 549–599

  • Shiohara M, Koike K, Komiyama A, Koeffler HP . 1997 Leuk. Lymphoma 26: 35–41

  • Sugiyama Y, Tomoda K, Tanaka T, Arata Y, Yoneda-Kato N, Kato J . 2001 J. Biol. Chem. 276: 12084–12090

  • Van Etten RA, Jackson PK, Baltimore D, Sanders MC, Matsudaira PT, Janmey PA . 1994 J. Cell Biol. 124: 325–340

  • Verfaillie CM . 1992 Blood 79: 2821–2826

  • Verfaillie CM, McCarthy JB, McGlave PB . 1992 J. Clin. Invest. 90: 1232–1241

  • Wertheim JA, Forsythe K, Druker BJ, Hammer D, Boettiger D, Pear WS . 2002 Blood 99: 4122–4130

  • Zhao RC, Jiang Y, Verfaillie CM . 2001 Blood 97: 2406–2412

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  1. Stem Cell Institute, Cancer Center, Minneapolis, 55455, Minnesota, MN, USA

    Stephanie Salesse & Catherine M Verfaillie

  2. Department of Medicine, University of Minnesota Cancer Center, Minneapolis, 55455, Minnesota, MN, USA

    Stephanie Salesse & Catherine M Verfaillie

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Correspondence to Catherine M Verfaillie.

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Salesse, S., Verfaillie, C. Mechanisms underlying abnormal trafficking and expansion of malignant progenitors in CML: BCR/ABL-induced defects in integrin function in CML. Oncogene 21, 8605–8611 (2002). https://doi.org/10.1038/sj.onc.1206088

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