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Published: 22 April 2005

BCR/ABL, mRNA translation and apoptosis

D Perrotti^1,2,
F Turturro³ &
P Neviani¹

Cell Death & Differentiation volume 12, pages 534–540 (2005)Cite this article

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Altered mRNA translation has been recently associated with malignant transformation of several cell types, including hematopoietic cells. The deregulated kinase activity of the BCR/ABL oncoproteins, hallmark of chronic myelogenous leukemia (CML), enhances proliferation and survival, and arrests differentiation of hematopoietic progenitors by aberrantly modulating the activity of signaling molecules that control gene transcription, induce post-translational modifications and regulate translation of mRNAs into functional proteins. In this review, we discuss the mechanisms whereby BCR/ABL, by altering the expression/function of specific RNA-binding proteins and the activity of the translational machinery, impairs maturation and decreases susceptibility to apoptosis of myeloid progenitors.

CML, a myeloproliferative disorder of the pluripotent bone marrow stem cell, involves the progression from an indolent ‘chronic phase’ (CML-CP) to the aggressive and fatal ‘blast crisis’ (CML-BC) marked by the clonal expansion of an immature population of differentiation-arrested myeloid or lymphoid blasts.^{1, 2} Pathognomonic for CML is the oncoprotein BCR/ABL,^{3, 4} the product of the translocation t(9;22)(q34;q11) designated as the Philadelphia chromosome (Ph¹).^{5, 6} The chronic phase, which lasts several years, is characterized by accumulation in the bone marrow and peripheral blood of myeloid precursors, showing markedly enhanced proliferative potential and reduced susceptibility to drug-induced apoptosis, while retaining the ability to terminally differentiate into mature cells. The terminal and fatal ‘blast crisis’ phase lasts only a few months and is characterized by the rapid expansion and accumulation of myeloid or lymphoid precursors that exhibit enhanced proliferation and survival, increased genomic instability, altered motility and trafficking, while being completely unable to terminally differentiate.⁷

References

Wong S and Witte ON (2004) Annu. Rev. Immunol. 22: 247–306
Calabretta B and Perrotti D (2004) Blood 103: 4010–4022
Ben-Neriah Y et al. (1986) Science 233: 212–214
Shtivelman E et al. (1986) Cell 47: 277–284
Nowell PC (1962) Blut 8: 65–66
Rowley JD (1973) Nature 243: 290–293
Kantarjian HM et al. (1987) Am. J. Med. 83: 445–454
Sawyers CL (1999) N. Engl. J. Med. 340: 1330–1340
McGahon A et al. (1994) Blood 83: 1179–1187
Cortez D et al. (1995) Mol. Cell. Biol. 15: 5531–5541
Bedi A et al. (1994) Blood 83: 2038–2044
Kantarjian HM et al. (1993) Blood 82: 691–703
Laneuville P et al. (1991) Oncogene 6: 275–282
Gaiger A et al. (1995) Blood 86: 2371–2378
Elmaagacli AH et al. (2000) Ann. Hematol. 79: 424–431
Jamieson CH et al. (2004) N. Engl. J. Med. 351: 657–667
O'Brien SG et al. (2003 N. Engl. J. Med. 348: 994–1004
Sawyers CL et al. (2002) Blood 99: 3530–3539
Shah NP and Sawyers CL. (2003) Oncogene 22: 7389–7395
Huntly BJ et al. (2004) Cancer Cell 6: 587–596
Varticovski L et al. (1991) Mol. Cell. Biol. 11: 1107–1113
Skorski T et al. (1997) EMBO J 16: 6151–6161
Skorski T et al. (1995) Blood 86: 726–736
Holland EC et al. (2004) Oncogene 23: 3138–3144
Vivanco I and Sawyers CL (2002) Nat. Rev. Cancer 2: 489–501
Datta SR et al. (1997) Cell 91: 231–241
Zhou BP et al. (2001) Nat. Cell Biol. 3: 973–982
Salomoni P et al. (2000) Blood 96: 676–684
Mayo LD and Donner DB (2001) Proc. Natl. Acad. Sci. USA 98: 11598–11603
Brunet A et al. (1999) Cell 96: 857–868
Chou MM et al. (1998) Curr. Biol. 8: 1069–1077
Miron M et al. (2001) Nat. Cell Biol. 3: 596–601
Franke TF et al. (1997) Science 275: 665–668
Ly C et al. (2003) Cancer Res. 63: 5716–5722
Montagne J et al. (1999) Science 285: 2126–2129
Hornstein E et al. (2001) Cold Spring Harb. Symp. Quant. Biol. 66: 477–484
Gingras AC et al. (1999) Annu. Rev. Biochem. 68: 913–963
Gingras AC et al. (1999) Genes Dev. 13: 1422–1437
Lazaris-Karatzas A et al. (1990) Nature 345: 544–547
Gopalkrishnan RV et al. (1999) Int. J. Biochem. Cell Biol. 31: 151–162
Gingras AC et al. (2004) Curr. Top. Microbiol. Immunol. 279: 169–197
Rosenwald IB et al. (1993) Proc. Natl. Acad. Sci. USA 90: 6175–6178
Mendez R et al. (1996) Mol. Cell. Biol. 16: 2857–2864
Muise-Helmericks RC et al. (1998) J. Biol. Chem. 273: 29864–29872
Afar DE et al. (1995) Proc. Natl. Acad. Sci. USA 92: 9540–9544
Sawyers CL et al. (1992) Cell 70: 901–910
Kleijn M et al. (1998) Eur. J. Biochem. 253: 531–544
Scheper GC et al. (2002) J. Biol. Chem. 277: 3303–3309
Waskiewicz AJ et al. (1997) EMBO J. 16: 1909–1920
Waskiewicz AJ et al. (1999) Mol. Cell. Biol. 19: 1871–1880
Moore JC et al. (2004) Blood 104: 1993
Topisirovic I et al. (2004) Cancer Res. 64: 8639–8642
Topisirovic I et al. (2003) Mol. Cell. Biol. 23: 8992–9002
Nimmanapalli R et al. (2003) Cancer Res. 63: 7950–7958
Perkins CL et al. (2000) Cancer Res. 60: 1645–1653
Porosnicu M et al. (2001) Leukemia 15: 772–778
La Rosee P et al. (2002) Exp. Hematol. 30: 729–737
Van Hoof C and Goris J. (2004) Cancer Cell. 5: 105–106
Janssens V and Goris J. (2001) Biochem. J. 353: 417–439
Chen W et al. (2004) Cancer Cell 5: 127–136
Sato S et al. (2000) Proc. Natl. Acad. Sci. USA 97: 10832–10837
Matsuoka Y et al. (2003) Br. J. Pharmacol. 138: 1303–1312
Peterson RT et al. (1999) Proc. Natl. Acad. Sci. USA 96: 4438–4442
Petritsch C et al. (2000) Genes Dev. 14: 3093–3101
Ahuja H et al. (1989) Proc. Natl. Acad. Sci. USA 86: 6783–6787
Ferrari S et al. (1989) Leukemia 3: 423–430
Kelman Z et al. (1989) Blood 74: 2318–2324
Hernandez A et al. (1993) Ann. Hematol. 66: 81–83
Neubauer A et al. (1993) Leukemia 7: 593–600
Skorski T et al. (1996) Proc. Natl. Acad. Sci. USA 93: 13137–13142
Gaidano G et al. (1997) Genes Chromosomes Cancer 19: 250–255
Trotta R et al. (2003) Cancer Cell 3: 145–160
Zhai W and Comai L. (2000) Mol. Cell. Biol. 20: 5930–5938
Budde A and Grummt I (1999) Oncogene 18: 1119–1124
Fontoura BM et al. (1997) Mol. Cell. Biol. 17: 3146–3154
Horton LE et al. (2002) Oncogene 21: 5325–5334
Druker BJ. (2004) Adv. Cancer Res. 91: 1–30
Raught B et al. (1996) Cancer Res. 56: 4382–4386
Lincoln AJ et al. (1998) J. Biol. Chem. 273: 9552–9560
Fu L et al. (1999) Oncogene 18: 6419–6424
Timchenko NA. (2003) Cell Cycle 2: 445–446
Calkhoven CF et al. (2000 Genes Dev. 14: 1920–1932
Nowicki MO et al. (2003) Oncogene 22: 3952–3963
Perrotti D et al. (1998) EMBO J. 17: 4442–4455
Perrotti D et al. (2002) Nat. Genet. 30: 48–58
Perrotti D et al. (2000) Mol. Cell. Biol. 20: 6159–6169
Iervolino A et al. (2002) Mol. Cell. Biol. 22: 2255–2266
Perrotti D and Calabretta B. (2002) Oncogene 21: 8577–8583
Notari M et al. (2003) Blood 102: 2412
Makeyev AV and Liebhaber SA (2002) RNA 8: 265–278
Blyn LB et al. (1997) J. Vorol. 71: 6243–6246
Graff J et al. (1998) J. Virol. 72: 9668–9675
Collier B et al. (1998) J. Biol. Chem. 273: 22648–22656
Ostareck DH et al. (1997) Cell 89: 597–606
Silvera D et al. (1999) J. Biol. Chem. 274: 38163–38170
Ostareck-Lederer A and Ostareck DH (2004) Biol. Cell. 96: 407–411
Bomsztyk K et al. (1997) FEBS Lett. 403: 113–115
Michael WM et al. (1997) EMBO J. 16: 3587–3598
Tomonaga T and Levens D (1996) Proc. Natl. Acad. Sci. USA 93: 5830–5835
Gaillard C et al. (1994) Nucleic Acids Res. 22: 4183–4186
Takimoto M et al. (1993) J. Biol. Chem. 268: 18249–18258
Lee MH et al. (1996) J. Biol. Chem. 271: 3420–3427
Michelotti GA et al. (1996) Mol. Cell. Biol. 16: 2656–2669
Miau LH et al. (1998) J. Biol .Chem. 273: 10784–10791
Bustelo XR et al. (1995) Mol. Cell. Biol. 15: 1324–1332
Taylor SJ and Shalloway D (1994) Nature 368: 867–871
Schullery DS et al. (1999) J. Biol. Chem. 274: 15101–15109
Habelhah H et al. (2001) Nat. Cell. Biol. 3: 325–330
Groysman M et al. (1998) Oncogene 17: 1597–1606
Ostareck-Lederer A et al. (2002) Mol. Cell. Biol. 22: 4535–4543
Ostareck DH et al. (2001) Cell 104: 281–290
Evans JR et al. (2003) Oncogene 22: 8012–8020
Matulonis U et al. (1993) Exp. Hematol. 21: 1460–1466
Skorski T et al. (1998) Blood 91: 406–418
Stewart MJ et al. (1995) Leukemia 9: 1499–1507
Xie S et al. (2002) Oncogene 21: 7137–7146
Ostrowski J et al. (2003) Nucleic Acids Res. 31: 3954–3962
Michelotti EF et al. (1995) J. Biol. Chem. 270: 9494–9499
Michelotti EF et al. (1996) Mol. Cell. Biol. 16: 2350–2360
Mandal M et al. (2001) J. Biol. Chem. 276: 9699–9704
Tenenbaum SA et al. (2002) Methods 26: 191–198
Keene JD and Tenenbaum SA (2002 Mol. Cell. 9: 1161–1167
Tenenbaum SA et al. (2000) Proc. Natl. Acad. Sci. USA 97: 14085–14090
Brown V et al. (2001) Cell 107: 477–487
Waggoner SA and Liebhaber SA. (2003) Mol. Cell. Biol. 23: 7055–7067
Zhang DE et al. (1997) Proc. Natl. Acad. Sci. USA 94: 569–574
Radomska HS et al. (1998) Mol. Cell. Biol. 18: 4301–4314
Cazzola M and Skoda RC (2000) Blood 95: 3280–3288
Thisted T et al. (2001) J. Biol. Chem. 276: 17484–17496
Ostareck-Lederer A, Ostareck DH and Hentze MW (1998) Trends Biochem. Sci. 23: 409–411
Biamonti G et al. (1993) J. Mol. Biol. 230: 77–89
Dreyfuss G et al. (1993) Annu. Rev. Biochem. 62: 289–321
Majewski M et al. (1999 Cancer Res. 59: 2815–2819
Nakanishi H et al. (1993) J. Biol. Chem. 268: 13–16
Municio MM et al. (1995) J. Biol. Chem. 270: 15884–15891
Shuai K et al. (1996) Oncogene 13: 247–254
Horita M et al. (2000) J. Exp. Med. 191: 977–984
Ilaria Jr. RL and Van Etten RA (1996) J. Biol. Chem. 271: 31704–31710
Carlesso N et al. (1996 J. Exp. Med. 183: 811–820
Frank DA and Varticovski L (1996) Leukemia 10: 1724–1730
Klejman A et al. (2002) EMBO J. 21: 5766–5774
Bonnal S et al. (2004) J. Biol. Chem. 280: 4144–4153
Fan H et al. (1998) Mol. Cell. Biol. 18: 3201–3211
Wolin SL and Cedervall T (2002) Annu. Rev. Biochem. 71: 375–403
Maraia RJ and Intine RV. (2001) Mol. Cell. Biol. 21: 367–379
Kim YK et al. (2001) Nucleic Acids Res. 29: 5009–5016
Holcik M and Korneluk RG (2000) Mol. Cell. Biol. 20: 4648–4657
Cardinali B et al. (2003) J. Biol. Chem. 278: 35145–35151
Intine RV et al. (2003) Mol. Cell. 12: 1301–1307
Schwartz EI et al. (2004) Mol. Cell. Biol. 24: 9580–9591
Mishra S et al. (2003) Oncogene 22: 8255–8262
Fang G et al. (2000) Blood 96: 2246–2253

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Acknowledgements

We thank Drs S Tiong Ong (U.C. Irvine, CA, USA) and B Calabretta (Thomas Jefferson University, Philadelphia PA) for communicating their data prior to publication and Ms. Abbey Carter for editorial assistance. This work was supported in part by grants from the National Cancer Institute CA095512 and CA16058, NIH, Bethesda MD; the US Army, Chronic Myelogenous Leukemia Research Program, DAMD17-03-1-0184; and The Lauri Strauss Leukemia Research Foundation.

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Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, USA
D Perrotti & P Neviani
The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
D Perrotti
Department of Medicine, Feist-Weiller Cancer Center, Gene Therapy Program, Louisiana State University Health Sciences Center, Shreveport, LA, USA
F Turturro

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Perrotti, D., Turturro, F. & Neviani, P. BCR/ABL, mRNA translation and apoptosis. Cell Death Differ 12, 534–540 (2005). https://doi.org/10.1038/sj.cdd.4401606

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Published: 22 April 2005
Issue date: 01 June 2005
DOI: https://doi.org/10.1038/sj.cdd.4401606

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