Skip to main content
SpringerLink
Log in
Book cover

Acute Leukemias pp 177–189Cite as

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

  • Chapter

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

Abstract

The Philadelphia chromosome (Ph) is the shortened chromosome 22 resulting from the reciprocal translocation between 5′ part of the BCR gene from chromosome 22 combines with the 3′ part of the ABL gene, resulting in an chimeric BCR-ABL tyrosine kinase that is constitutively activated and oncogenic. The Ph is the genetic hallmark of chronic myeloid leukemia (CML), and it is also the most frequent cytogenetic abnormality in adult acute lymphoblastic leukemia (Ph+ ALL), where it is present in roughly 25% of cases. The Ph occurs less often in pediatric ALL, with a prevalence of <5%. In both age groups the Ph chromosome describes a subgroup of ALL with a poor prognosis. Thus, patients with Ph+ ALL are usually offered a hematopoietic stem cell transplant if a suitable donor is available. The tyrosine kinase inhibitor, imatinib mesylate, has been found to block the activity of the BCR-ABL tyrosine kinase and has made an impact in the short-term management of Ph+ ALL. Unfortunately the effect of Imatinib monotherapy tends to be short-lived in Ph+ ALL, and it is by no means curative.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   189.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Rubin CM, Carrino JJ, Dickler MN, Leibowitz D, Smith SD, Westbrook CA (1988) Heterogeneity of genomic fusion of BCR and ABL in Philadelphia chromosome-positive acute lymphoblastic leukemia. Proc Natl Acad Sci 85(8):2795–2799

    Article  PubMed  CAS  Google Scholar 

  2. Kurzrock R, Shtalrid M, Gutterman JU, Koller CA, Walters R, Trujillo JM, et al. (1987) Molecular analysis of chromosome 22 breakpoints in adult Philadelphia-positive acute lymphoblastic leukaemia. Br J Haematol 67(1):55–59

    PubMed  CAS  Google Scholar 

  3. Hooberman AL, Carrino JJ, Leibowitz D, Rowley JD, Le Beau MM, Arlin ZA, et al. (1989) Unexpected heterogeneity of BCR-ABL fusion mRNA detected by polymerase chain reaction in Philadelphia chromosome-positive acute lymphoblastic leukemia. Proc Natl Acad Sci 86(11):4259–4263

    Article  PubMed  CAS  Google Scholar 

  4. Hermans A, Heisterkamp N, von Linden M, van Baal S, Meijer D, van der Plas D, et al. (1987) Unique fusion of bcr and c-abl genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell 51(1):33–40

    Article  PubMed  CAS  Google Scholar 

  5. Gehly GB, Bryant EM, Lee AM, Kidd PG, Thomas ED (1991) Chimeric BCR-abl messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 78(2):458–465

    PubMed  CAS  Google Scholar 

  6. Maurer J, Kinzel H, Nentwig T, Thiel E (1990) Molecular diagnosis of the Philadelphia chromosome in chronic myelogenous and acute lymphoblastic leukemias by PCR. Dis Markers 8(4):211–218

    PubMed  CAS  Google Scholar 

  7. Okamoto K, Karasawa M, Sakai H, Ogura H, Morita K, Naruse T (1997) A novel acute lymphoid leukaemia type BCR/ABL transcript in chronic myelogenous leukaemia. Br J Haematol 96(3):611–613

    Article  PubMed  CAS  Google Scholar 

  8. Inukai T, Sugita K, Suzuki T, Ijima K, Goi K, Tezuka T, et al. (1993) A novel 203 kD aberrant BCR-ABL product in a girl with Philadelphia chromosome positive acute lymphoblastic leukaemia. Br J Haematol 85(4):823–825

    PubMed  CAS  Google Scholar 

  9. Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV (1991) Philadelphia positive acute lymphoblastic leukemia in adults: Age distribution, BCR breakpoint and prognostic significance. Leukemia 5(3):196–199

    PubMed  CAS  Google Scholar 

  10. Radich J, Gehly G, Lee A, Avery R, Bryant E, Edmands S, et al. (1997) Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation. Blood 89(7):2602–2609

    PubMed  CAS  Google Scholar 

  11. Saglio G, Pane F, Gottardi E, Frigeri F, Buonaiuto MR, Guerrasio A, et al. (1996) Consistent amounts of acute leukemia-associated P190BCR/ABL transcripts are expressed by chronic myelogenous leukemia patients at diagnosis. Blood 87(3):1075–1080

    PubMed  CAS  Google Scholar 

  12. Lichty BD, Keating A, Callum J, Yee K, Croxford R, Corpus G, et al. (1998) Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia. Br J Haematol 103(3):711–715

    Article  PubMed  CAS  Google Scholar 

  13. Secker-Walker LM, Cooke HM, Browett PJ, Shippey CA, Norton JD, Coustan-Smith E, et al. (1988) Variable Philadelphia breakpoints and potential lineage restriction of bcr rearrangement in acute lymphoblastic leukemia. Blood 72(2):784–791

    PubMed  CAS  Google Scholar 

  14. Haferlach T, Winkemann M, Ramm-Petersen L, Meeder M, Schoch R, Weber-Matthiesen K, et al. (1997) New insights into the biology of Philadelphia-chromosome-positive acute lymphoblastic leukaemia using a combination of May-Grunwald-Giemsa staining and fluorescence in situ hybridization techniques at the single cell level. Br J Haematol 99(2):452–459

    Article  PubMed  CAS  Google Scholar 

  15. Anastasi J, Feng J, Dickstein JI, Le Beau MM, Rubin CM, Larson RA, et al. (1996) Lineage involvement by BCR/ABL in Ph+ lymphoblastic leukemias: Chronic myelogenous leukemia presenting in lymphoid blast vs Ph+ acute lymphoblastic leukemia. Leukemia 10(5):795–802

    PubMed  CAS  Google Scholar 

  16. Estrov Z, Talpaz M, Kantarjian HM, Zipf TF, McClain KL, Kurzrock R (1993) Heterogeneity in lineage derivation of Philadelphia-positive acute lymphoblastic leukemia expressing p190BCR-ABL or p210BCR-ABL: Determination by analysis of individual colonies with the polymerase chain reaction. Cancer Res 53(14):3289–3293

    PubMed  CAS  Google Scholar 

  17. Secker-Walker LM, Craig JM (1993) Prognostic implications of breakpoint and lineage heterogeneity in Philadelphia-positive acute lymphoblastic leukemia: A review. Leukemia 7(2):147–151

    PubMed  CAS  Google Scholar 

  18. Craig JM, Hawkins JM, Yamada T, Ganeshaguru K, Mehta AB, Secker-Walker LM (1990) First intron and M-bcr breakpoints are restricted to the lymphoid lineage in Philadelphia positive acute lymphoblastic leukemia. Leukemia 4(10):678–681

    PubMed  CAS  Google Scholar 

  19. Pajor L, Vass JA, Kereskai L, Kajtar P, Szomor A, Egyed M, et al. (2000) The existence of lymphoid lineage restricted Philadelphia chromosome-positive acute lymphoblastic leukemia with heterogeneous bcr-abl rearrangement. Leukemia 14(6):1122–1126

    Article  PubMed  CAS  Google Scholar 

  20. Kasprzyk A, Harrison CJ, Secker-Walker LM (1999) Investigation of clonal involvement of myeloid cells in Philadelphia-positive and high hyperdiploid acute lymphoblastic leukemia. Leukemia 13(12):2000–2006

    Article  PubMed  CAS  Google Scholar 

  21. Castor A, Nilsson L, Astrand-Grundstrom I, Buitenhuis M, Ramirez C, Anderson K, et al. (2005) Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nat Med 11(6):630–637

    Article  PubMed  CAS  Google Scholar 

  22. Schenk TM, Keyhani A, Bottcher S, Kliche KO, Goodacre A, Guo JQ, et al. (1998) Multilineage involvement of Philadelphia chromosome positive acute lymphoblastic leukemia. Leukemia 12(5): 666–674

    Article  PubMed  CAS  Google Scholar 

  23. Cobaleda C, Gutierrez-Cianca N, Perez-Losada J, Flores T, Garcia-Sanz R, Gonzalez M, et al. (2000) A primitive hematopoietic cell is the target for the leukemic transformation in human philadelphia-positive acute lymphoblastic leukemia. Blood 95(3): 1007–1013

    PubMed  CAS  Google Scholar 

  24. Hotfilder M, Rottgers S, Rosemann A, Schrauder A, Schrappe M, Pieters R, et al. (2005) Leukemic stem cells in childhood high-risk ALL/t(9;22) and t(4;11) are present in primitive lymphoid-restricted CD34+CD19-cells. Cancer Res 65(4):1442–1449

    Article  PubMed  CAS  Google Scholar 

  25. Voncken JW, Morris C, Pattengale P, Dennert G, Kikly C, Groffen J, et al. (1992) Clonal development and karyotype evolution during leukemogenesis of BCR/ABL transgenic mice. Blood 79(4):1029–1036

    PubMed  CAS  Google Scholar 

  26. Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J (1990) Acute leukaemia in bcr/abl transgenic mice. Nature 344(6263):251–253

    Article  PubMed  CAS  Google Scholar 

  27. Voncken JW, Kaartinen V, Pattengale PK, Germeraad WT, Groffen J, Heisterkamp N (1995) BCR/ABL P210 and P190 cause distinct leukemia in transgenic mice. Blood 86(12):4603–4611

    PubMed  CAS  Google Scholar 

  28. Pear WS, Miller JP, Xu L, Pui JC, Soffer B, Quackenbush RC, et al. (1998) Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow. Blood 92(10):3780–3792

    PubMed  CAS  Google Scholar 

  29. Wetzler M, Talpaz M, Van Etten RA, Hirsh-Ginsberg C, Beran M, Kurzrock R (1993) Subcellular localization of Bcr, Abl, and Bcr-Abl proteins in normal and leukemic cells and correlation of expression with myeloid differentiation. J Clin Invest 92(4):1925–1939

    PubMed  CAS  Google Scholar 

  30. Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci PG, et al. (1994) Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway. EMBO J 13(4):764–773

    PubMed  CAS  Google Scholar 

  31. Sexl V, Piekorz R, Moriggl R, Rohrer J, Brown MP, Bunting KD, et al. (2000) Stat5a/b contribute to interleukin 7-induced B-cell precursor expansion, but abl-and bcr/abl-induced transformation are independent of stat5. Blood 96(6):2277–2283

    PubMed  CAS  Google Scholar 

  32. Gotoh A, Miyazawa K, Ohyashiki K, Toyama K (1994) Potential molecules implicated in downstream signaling pathways of p185BCR-ABL in Ph+ ALL involve GTPase-activating protein, phospholipase C-gamma 1, and phosphatidylinositol 3′-kinase. Leukemia 8(1):115–120

    PubMed  CAS  Google Scholar 

  33. Amarante-Mendes GP, Naekyung Kim C, Liu L, Huang Y, Perkins CL, Green DR, et al. (1998) Bcr-Abl exerts its antiapoptotic effect against diverse apoptotic stimuli through blockage of mitochondrial release of cytochrome C and activation of caspase-3. Blood 91(5):1700–1705

    PubMed  CAS  Google Scholar 

  34. Lewis JM, Baskaran R, Taagepera S, Schwartz MA, Wang JY (1996) Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic-nuclear transport. Proc Natl Acad Sci 93(26): 15174–15179

    Article  PubMed  CAS  Google Scholar 

  35. Verfaillie CM, Hurley R, Zhao RC, Prosper F, Delforge M, Bhatia R (1997) Pathophysiology of CML: Do defects in integrin function contribute to the premature circulation and massive expansion of the BCR/ABL positive clone? J Lab Clin Med 129(6):584–591

    Article  PubMed  CAS  Google Scholar 

  36. Hu Y, Liu Y, Pelletier S, Buchdunger E, Warmuth M, Fabbro D, et al. (2004) Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat Genet 36(5):453–461

    Article  PubMed  CAS  Google Scholar 

  37. Lugo TG, Pendergast AM, Muller AJ, Witte ON (1990) Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 247(4946):1079–1082

    Article  PubMed  CAS  Google Scholar 

  38. Li S, Ilaria RL, Jr., Million RP, Daley GQ, Van Etten RA (1999) The P190, P210, and P230forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. J Exp Med 189(9):1399–1412

    Article  PubMed  CAS  Google Scholar 

  39. Ilaria RL, Jr, Van Etten RA (1996) P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members. J Biol Chem 271(49):31704–31710

    Article  PubMed  CAS  Google Scholar 

  40. Radich JP, Kopecky KJ, Boldt DH, Head D, Slovak ML, Babu R, et al. (1994) Detection of BCR-ABL fusion genes in adult acute lymphoblastic leukemia by the polymerase chain reaction. Leukemia 8(10):1688–1695

    PubMed  CAS  Google Scholar 

  41. Stirewalt DL, Guthrie KA, Beppu L, Bryant EM, Doney K, Gooley T, et al. (2003) Predictors of relapse and overall survival in Philadelphia chromosome-positive acute lymphoblastic leukemia after transplantation. Biol Blood Marrow Transplant 9(3):206–212

    Article  PubMed  Google Scholar 

  42. Arico M, Valsecchi MG, Camitta B, Schrappe M, Chessells J, Baruchel A, et al. (2000) Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med 342(14):998–1006

    Article  PubMed  CAS  Google Scholar 

  43. Gleissner B, Gokbuget N, Bartram CR, Janssen B, Rieder H, Janssen JW, et al. (2002) Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: A prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 99(5): 1536–1543

    Article  PubMed  CAS  Google Scholar 

  44. Pui CH, Relling MV, Downing JR (2004) Acute lymphoblastic leukemia. N Engl J Med 350(15):1535–1548

    Article  PubMed  CAS  Google Scholar 

  45. Roy A, Bradburn M, Moorman AV, Burrett J, Love S, Kinsey SE, et al. (2005) Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia: Results of the Medical Research Council ALL 97 trial. Br J Haematol 129(1):35–44

    Article  PubMed  Google Scholar 

  46. Pui CH, Sandlund JT, Pei D, Campana D, Rivera GK, Ribeiro RC, et al. (2004) Improved outcome for children with acute lymphoblastic leukemia: Results of Total Therapy Study XIIIB at St Jude Children’s Research Hospital. Blood 104(9):2690–2696

    Article  PubMed  CAS  Google Scholar 

  47. Arico M, Valsecchi MG, Conter V, Rizzari C, Pession A, Messina C, et al. (2002) Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone-poor response treated with double Berlin-Frankfurt-Muenster protocol II. Blood 100(2):420–426

    Article  PubMed  CAS  Google Scholar 

  48. Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, et al. (2001) Improved outcome for children with acute lymphoblastic leukemia: Results of Dana-Farber Consortium Protocol 91-01. Blood 97(5):1211–1218

    Article  PubMed  CAS  Google Scholar 

  49. Crist W, Carroll A, Shuster J, Jackson J, Head D, Borowitz M, et al. (1990) Philadelphia chromosome positive childhood acute lymphoblastic leukemia: Clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study. Blood 76(3):489–494

    PubMed  CAS  Google Scholar 

  50. Uckun FM, Nachman JB, Sather HN, Sensel MG, Kraft P, Steinherz PG, et al. (1998) Clinical significance of Philadelphia chromosome positive pediatric acute lymphoblastic leukemia in the context of contemporary intensive therapies: A report from the Children’s Cancer Group. Cancer 83(9):2030–2039

    Article  PubMed  CAS  Google Scholar 

  51. Schrappe M, Arico M, Harbott J, Biondi A, Zimmermann M, Conter V, et al. (1998) Philadelphia chromosome-positive (Ph+) childhood acute lymphoblastic leukemia: Good initial steroid response allows early prediction of a favorable treatment outcome. Blood 92(8):2730–2741

    PubMed  CAS  Google Scholar 

  52. Schlieben S, Borkhardt A, Reinisch I, Ritterbach J, Janssen JW, Ratei R, et al. (1996) Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05-92. Leukemia 10(6):957–963

    PubMed  CAS  Google Scholar 

  53. Ribeiro RC, Broniscer A, Rivera GK, Hancock ML, Raimondi SC, Sandlund JT, et al. (1997) Philadelphia chromosome-positive acute lymphoblastic leukemia in children: Durable responses to chemotherapy associated with low initial white blood cell counts. Leukemia 11(9):1493–1496

    Article  PubMed  CAS  Google Scholar 

  54. Forestier E, Johansson B, Gustafsson G, Borgstrom G, Kerndrup G, Johannsson J, et al. (2000) Prognostic impact of karyotypic findings in childhood acute lymphoblastic leukaemia: A Nordic series comparing two treatment periods. For the Nordic Society of Paediatric Haematology and Oncology (NOPHO) Leukaemia Cytogenetic Study Group. Br J Haematol 110(1):147–153

    Article  PubMed  CAS  Google Scholar 

  55. Hann I, Vora A, Harrison G, Harrison C, Eden O, Hill F, et al. (2001) Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: Results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol. Br J Haematol 113(1):103–114

    Article  PubMed  CAS  Google Scholar 

  56. Mori T, Manabe A, Tsuchida M, Hanada R, Yabe H, Ohara A, et al. (2001) Allogeneic bone marrow transplantation in first remission rescues children with Philadelphia chromosome-positive acute lymphoblastic leukemia: Tokyo Children’s Cancer Study Group (TCCSG) studies L89-12 and L92-13. Med Pediatr Oncol 37(5):426–431

    Article  PubMed  CAS  Google Scholar 

  57. Sharathkumar A, Saunders EF, Dror Y, Grant R, Greenberg M, Weitzman S, et al. (2004) Allogeneic bone marrow transplantation vs. chemotherapy for children with Philadelphia chromosome-positive acute lymphoblastic leukemia. Bone Marrow Transplant 33(1):39–45

    Article  PubMed  CAS  Google Scholar 

  58. Mastrangelo R, Poplack D, Bleyer A, Riccardi R, Sather H, D’Angio G (1986) Report and recommendations of the Rome workshop concerning poor-prognosis acute lymphoblastic leukemia in children: Biologic bases for staging, stratification, and treatment. Med Pediatr Oncol 14(3):191–194

    Article  PubMed  CAS  Google Scholar 

  59. Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P, et al. (1996) Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol 14(1):18–24

    PubMed  CAS  Google Scholar 

  60. Heerema NA, Harbott J, Galimberti S, Camitta BM, Gaynon PS, Janka-Schaub G, et al. (2004) Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome. Leukemia 18(4):693–702

    Article  PubMed  CAS  Google Scholar 

  61. Riehm H, Reiter A, Schrappe M, Berthold F, Dopfer R, Gerein V, et al. (1987) [Corticosteroid-dependent reduction of leukocyte count in blood as a prognostic factor in acute lymphoblastic leukemia in childhood (therapy study ALL-BFM 83)]. Klin Padiatr 199(3):151–160

    Article  PubMed  CAS  Google Scholar 

  62. Hongo T, Okada S, Inoue N, Yamada S, Yajima S, Watanabe C, et al. (2002) Two groups of Philadelphia chromosome-positive childhood acute lymphoblastic leukemia classified by pretreatment multidrug sensitivity or resistance in in vitro testing. Int J Hematol 76(3):251–259

    PubMed  Google Scholar 

  63. Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, et al. (2002) Treatment of adult acute lymphoblastic leukemia (ALL): Long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood 99(3):863–871

    Article  PubMed  CAS  Google Scholar 

  64. Faderl S, Kantarjian HM, Thomas DA, Cortes J, Giles F, Pierce S, et al. (2000) Outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia. Leuk Lymphoma 36(3–4):263–273

    Article  PubMed  CAS  Google Scholar 

  65. Secker-Walker LM, Prentice HG, Durrant J, Richards S, Hall E, Harrison G (1997) Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA. MRC Adult Leukaemia Working Party. Br J Haematol 96(3):601–610

    Article  PubMed  CAS  Google Scholar 

  66. Thomas X, Thiebaut A, Olteanu N, Danaila C, Charrin C, Archimbaud E, et al. (1998) Philadelphia chromosome positive adult acute lymphoblastic leukemia: Characteristics, prognostic factors and treatment outcome. Hematol Cell Ther 40(3):119–128

    PubMed  CAS  Google Scholar 

  67. Westbrook CA, Hooberman AL, Spino C, Dodge RK, Larson RA, Davey F, et al. (1992) Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: A Cancer and Leukemia Group B Study (8762). Blood 80(12):2983–2990

    PubMed  CAS  Google Scholar 

  68. Camera A, Annino L, Chiurazzi F, Fazi P, Cascavilla N, Fabbiano F, et al. (2004) GIMEMA ALL — Rescue 97: A salvage strategy for primary refractory or relapsed adult acute lymphoblastic leukemia. Haematologica 89(2):145–153

    PubMed  CAS  Google Scholar 

  69. Preti HA, O’Brien S, Giralt S, Beran M, Pierce S, Kantarjian HM (1994) Philadelphia-chromosome-positive adult acute lymphocytic leukemia: Characteristics, treatment results, and prognosis in 41 patients. Am J Med 97(1):60–65

    Article  PubMed  CAS  Google Scholar 

  70. Wetzler M, Dodge RK, Mrozek K, Stewart CC, Carroll AJ, Tantravahi R, et al. (2004) Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia: A study of the Cancer and Leukaemia Group B. Br J Haematol 124(3):275–288

    Article  PubMed  Google Scholar 

  71. Rieder H, Ludwig WD, Gassmann W, Maurer J, Janssen JW, Gokbuget N, et al. (1996) Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia. Br J Haematol 95(4):678–691

    Article  PubMed  CAS  Google Scholar 

  72. Primo D, Tabernero MD, Perez JJ, Rasillo A, Sayagues JM, Espinosa AB, et al. (2005) Genetic heterogeneity of BCR/ABL+ adult B-cell precursor acute lymphoblastic leukemia: Impact on the clinical, biological and immunophenotypical disease characteristics. Leukemia 19(5):713–720

    Article  PubMed  CAS  Google Scholar 

  73. Ko BS, Tang JL, Lee FY, Liu MC, Tsai W, Chen YC, et al. (2002) Additional chromosomal abnormalities and variability of BCR breakpoints in Philadelphia chromosome/BCR-ABL-positive acute lymphoblastic leukemia in Taiwan. Am J Hematol 71(4): 291–299

    Article  PubMed  CAS  Google Scholar 

  74. Dombret H, Gabert J, Boiron JM, Rigal-Huguet F, Blaise D, Thomas X, et al. (2002) Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia-results of the prospective multicenter LALA-94 trial. Blood 100(7):2357–2366

    Article  PubMed  CAS  Google Scholar 

  75. Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, et al. (2004) Outcome of treatment in adults with acute lymphoblastic leukemia: Analysis of the LALA-94 trial. J Clin Oncol 22(20):4075–4086

    Article  PubMed  CAS  Google Scholar 

  76. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, et al. (2001) Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344(14):1038–1042

    Article  PubMed  CAS  Google Scholar 

  77. Champagne MA, Capdeville R, Krailo M, Qu W, Peng B, Rosamilia M, et al. (2004) Imatinib mesylate (STI571) for treatment of children with Philadelphia chromosome-positive leukemia: Results from a Children’s Oncology Group phase 1 study. Blood 104(9):2655–2660

    Article  PubMed  CAS  Google Scholar 

  78. Ottmann OG, Druker BJ, Sawyers CL, Goldman JM, Reiffers J, Silver RT, et al. (2002) A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 100(6):1965–1971

    Article  PubMed  CAS  Google Scholar 

  79. Takayama N, Sato N, O’Brien SG, Ikeda Y, Okamoto S (2002) Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid. Br J Haematol 119(1):106–108

    Article  PubMed  Google Scholar 

  80. Thomas DA, Faderl S, Cortes J, O’Brien S, Giles FJ, Kornblau SM, et al. (2004) Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103(12):4396–4407

    Article  PubMed  CAS  Google Scholar 

  81. Leis JF, Stepan DE, Curtin PT, Ford JM, Peng B, Schubach S, et al. (2004) Central nervous system failure in patients with chronic myelogenous leukemia lymphoid blast crisis and Philadelphia chromosome positive acute lymphoblastic leukemia treated with imatinib (STI-571). Leuk Lymphoma 45(4):695–698

    Article  PubMed  CAS  Google Scholar 

  82. Lee KH, Lee JH, Choi SJ, Seol M, Lee YS, Kim WK, et al. (2005) Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Leukemia 19(9):1509–1516

    Article  PubMed  CAS  Google Scholar 

  83. Towatari M, Yanada M, Usui N, Takeuchi J, Sugiura I, Takeuchi M, et al. (2004) Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia. Blood 104(12):3507–3512

    Article  PubMed  CAS  Google Scholar 

  84. Lee S, Kim YJ, Min CK, Kim HJ, Eom KS, Kim DW, et al. (2005) The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 105(9):3449–3457

    Article  PubMed  CAS  Google Scholar 

  85. Lee S, Kim DW, Kim YJ, Chung NG, Kim YL, Hwang JY, et al. (2003) Minimal residual disease-based role of imatinib as a first-line interim therapy prior to allogeneic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 102(8):3068–3070

    Article  PubMed  CAS  Google Scholar 

  86. Wassmann B, Pfeifer H, Stadler M, Bornhauser M, Bug G, Scheuring UJ, et al. (2005) Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphiapositive acute lymphoblastic leukemia (Ph+ ALL). Blood 106(2): 458–463

    Article  PubMed  CAS  Google Scholar 

  87. von Bubnoff N, Peschel C, Duyster J (2003) Resistance of Philadelphia-chromosome positive leukemia towards the kinase inhibitor imatinib (STI571, Glivec): A targeted oncoprotein strikes back. Leukemia 17(5):829–838

    Article  CAS  Google Scholar 

  88. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, et al. (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293(5531): 876–880

    Article  PubMed  CAS  Google Scholar 

  89. Hato T, Yamanouchi J, Tamura T, Hojo N, Niiya Y, Kohno M, et al. (2004) Existence of leukemic clones resistant to both imatinib mesylate and rituximab before drug therapies in a patient with Philadelphia chromosome-positive acute lymphocytic leukemia. Int J Hematol 80(1):62–66

    Article  PubMed  Google Scholar 

  90. Hofmann WK, Komor M, Wassmann B, Jones LC, Gschaidmeier H, Hoelzer D, et al. (2003) Presence of the BCR-ABL mutation Glu255Lys prior to STI571 (imatinib) treatment in patients with Ph+ acute lymphoblastic leukemia. Blood 102(2):659–661

    Article  PubMed  CAS  Google Scholar 

  91. Weisberg E, Manley PW, Breitenstein W, Bruggen J, Cowan-Jacob SW, Ray A, et al. (2005) Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 7(2):129–141

    Article  PubMed  CAS  Google Scholar 

  92. Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL (2004) Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305(5682):399–401

    Article  PubMed  CAS  Google Scholar 

  93. Harata M, Soda Y, Tani K, Ooi J, Takizawa T, Chen M, et al. (2004) CD19-targeting liposomes containing imatinib efficiently kill Philadelphia chromosome-positive acute lymphoblastic leukemia cells. Blood 104(5):1442–1449

    Article  PubMed  CAS  Google Scholar 

  94. Barrett AJ HM, Ash RC, Atkinson K, Gale RP, Goldman JM, Henslee-Downey PJ, Herzig RH, Speck B, Zwaan FE, et al. (1992) Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 79(30):67–70

    Google Scholar 

  95. Dunlop LC PR, Singhal S, Treleaven JG, Swansbury GJ, Meller S, Pinkerton CR, Horton C, Mehta J (1996) Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Bone Marrow Transplant 17(36):5–9

    Google Scholar 

  96. Kroger N, Kruger W, Wacker-Backhaus G, Hegewisch-Becker S, Stockschlader M, Fuchs N, et al. (1998) Intensified conditioning regimen in bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Bone Marrow Transplant 22(11):1029–1033

    Article  PubMed  CAS  Google Scholar 

  97. Esperou H, Boiron JM, Cayuela JM, Blanchet O, Kuentz M, Jouet JP, et al. (2003) A potential graft-versus-leukemia effect after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Results from the French Bone Marrow Transplantation Society. Bone Marrow Transplant 31(10):909–918

    Article  PubMed  CAS  Google Scholar 

  98. Lee S, Kim DW, Cho B, Kim YJ, Kim YL, Hwang JY, et al. (2003) Risk factors for adults with Philadelphia-chromosome-positive acute lymphoblastic leukaemia in remission treated with allogeneic bone marrow transplantation: The potential of real-time quantitative reverse-transcription polymerase chain reaction. Br J Haematol 120(1):145–153

    Article  PubMed  CAS  Google Scholar 

  99. Matsue K, Tabayashi T, Yamada K, Takeuchi M (2002) Eradication of residual bcr-abl-positive clones by inducing graft-versus-host disease after allogeneic stem cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Bone Marrow Transplant 29(1):63–66

    Article  PubMed  CAS  Google Scholar 

  100. Sierra J, Radich J, Hansen JA, Martin PJ, Petersdorf EW, Bjerke J, et al. (1997) Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 90(4):1410–1414

    PubMed  CAS  Google Scholar 

  101. Snyder DS, Nademanee AP, O’Donnell MR, Parker PM, Stein AS, Margolin K, et al.(1999) Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission. Leukemia 13(12):2053–2058

    Article  PubMed  CAS  Google Scholar 

  102. Chao NJ, Blume KG, Forman SJ, Snyder DS (1995) Long-term follow-up of allogeneic bone marrow recipients for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 85(11):3353–3354

    PubMed  CAS  Google Scholar 

  103. Preudhomme C, Henic N, Cazin B, Lai JL, Bertheas MF, Vanrumbeke M, et al. (1997) Good correlation between RT-PCR analysis and relapse in Philadelphia (Ph1)-positive acute lymphoblastic leukemia (ALL). Leukemia 11(2):294–298

    Article  PubMed  CAS  Google Scholar 

  104. Pane F, Cimino G, Izzo B, Camera A, Vitale A, Quintarelli C, et al. (2005) Significant reduction of the hybrid BCR/ABL transcripts after induction and consolidation therapy is a powerful predictor of treatment response in adult Philadelphia-positive acute lymphoblastic leukemia. Leukemia 19(4):628–635

    PubMed  CAS  Google Scholar 

  105. Mitterbauer G, Nemeth P, Wacha S, Cross NC, Schwarzinger I, Jaeger U, et al. (1999) Quantification of minimal residual disease in patients with BCR-ABL-positive acute lymphoblastic leukaemia using quantitative competitive polymerase chain reaction. Br J Haematol 106(3):634–643

    Article  PubMed  CAS  Google Scholar 

  106. Scheuring UJ, Pfeifer H, Wassmann B, Bruck P, Atta J, Petershofen EK, et al. (2003) Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571). Blood 101(1):85–90

    Article  PubMed  CAS  Google Scholar 

  107. Scheuring UJ, Pfeifer H, Wassmann B, Bruck P, Gehrke B, Petershofen EK, et al. (2003) Serial minimal residual disease (MRD) analysis as a predictor of response duration in Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) during imatinib treatment. Leukemia 17(9):1700–1706

    Article  PubMed  CAS  Google Scholar 

  108. Miyamura K, Tanimoto M, Morishima Y, Horibe K, Yamamoto K, Akatsuka M, et al. (1992) Detection of Philadelphia chromosomepositive acute lymphoblastic leukemia by polymerase chain reaction: Possible eradication of minimal residual disease by marrow transplantation. Blood 79(5):1366–1370

    PubMed  CAS  Google Scholar 

  109. Kohler S, Galili N, Sklar JL, Donlon TA, Blume KG, Cleary ML (1990) Expression of bcr-abl fusion transcripts following bone marrow transplantation for Philadelphia chromosome-positive leukemia. Leukemia 4(8):541–547

    PubMed  CAS  Google Scholar 

  110. Knechtli CJ, Goulden NJ, Hancock JP, Grandage VL, Harris EL, Garland RJ, et al. (1998) Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia. Blood 92(11):4072–4079

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Olga Sala-Torra & Jerald P. Radich

Authors
  1. Olga Sala-Torra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jerald P. Radich
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Berlin Heidelberg

About this chapter

Cite this chapter

Sala-Torra, O., Radich, J.P. (2008). Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. In: Acute Leukemias. Hematologic Malignancies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-72304-2_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-72304-2_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-72302-8

  • Online ISBN: 978-3-540-72304-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation