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Expert Review of Molecular Diagnostics Volume 13, 2013 - Issue 7
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Theme: General - Review

BCR–ABL PCR testing in chronic myelogenous leukemia: molecular diagnosis for targeted cancer therapy and monitoring

Martin H LuuDepartment of Pathology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
&
Richard D PressDepartment of Pathology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA;Knight Cancer Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USACorrespondence[email protected]
Pages 749-762 | Published online: 09 Jan 2014

References

  • Vardiman JW, Melo JV, Baccarani M et al. Chronic myelogenous leukaemia, BCR–ABLABL1 positive. In: WHO classification of tumours of haematopoietic and lymphoid tissues (4th Edition). Swerdlow SH, Campo E, Harris NL et al. ( Eds). IARC Press, Lyon, France, 32–37 (2008).
  • Rowley JK. A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290–293 (1973).
  • Deininger MWN, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood 96(10), 3343–3356 (2000).
  • Nowell P, Hungerford D. A minute chromosome in human chronic granulocytic leukemia [abstract]. Science 132, 1497 (1960).
  • Melo JV. The diversity of BCR–ABLABL fusion proteins and their relationship to leukemia phenotype. Blood 88(7), 2375–2384 (1996).
  • Davis RL, Konopka JB, Witte ON. Activation of the c-ABL oncogene by viral transduction or chromosomal translocation generates altered c-ABL proteins with similar in vitro kinase properties. Mol. Cell. Biol. 5(1), 204–213 (1985).
  • Lugo TG, Pendergast AM, Muller AJ et al. Tyrosine kinase activity and transformation potency of BCR–ABL oncogene products. Science 247(4946), 1079–1082 (1990).
  • Melo JV, Gordon De, Cross NC et al. The ABL-BCR fusion gene is expressed in chronic myeloid leukemia. Blood 81(1), 158–165 (1993).
  • Kawasaki ES, Clark SS, Coyne MY et al. Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. Proc. Natl Acad. Sci. USA 85(15), 5698–5702 (1988).
  • Saglio G, Guerrasio A, Rosso C et al. New type of BCR/ABL junction in Philadelphia chromosome-positive chronic myelogenous leukemia. Blood 76(9), 1819–1824 (1990).
  • Li S, Ilaria RLJr, Million RP et al. The p190, p210, and p230 forms 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 (1999).
  • Tuszynski A, Dhut S, Young BD et al. Detection and significance of BCR–ABL mRNA transcripts and fusion proteins in Philadelphia-positive adult acute lymphoblastic leukemia. Leukemia 7(10), 1504–1508 (1993).
  • Crist W, Carroll A, Shuster J et al. Philadelphia chromosome positive childhood acute lymphoblastic leukemia: clinical and cytogenetic characteristics and treatment outcome. A pediatric oncology group study. Blood 76(3), 489–494 (1990).
  • Fialkow PJ, Jacobson RJ, Papyannopoulou T. Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. Am. J. Med. 63(1), 125–130 (1977).
  • O’Brien SG, Guilhot F, Larson RA et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 348, 994–1004 (2003).
  • Hughes TP, Kaeda J, Branford S et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N. Engl. J. Med. 349, 1423–1432 (2003).
  • Hughes T, Deininger M, Hochhaus A et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR–ABL transcripts and kinase domain mutations and for expressing results. Blood 108(1), 28–37 (2006).
  • Kantarjian H, Schiffer C, Jones D et al. Monitoring the response and course of chronic myeloid leukemia in the modern era of BCR–ABL tyrosine kinase inhibitors: practical advice on the use and interpretation of monitoring methods. Blood 111(4), 1774–1780 (2008).
  • Kantarjian H, Sawyers C, Hochhaus A et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N. Engl. J. Med. 346, 645–652 (2002).
  • Druker BJ, Guilhot F, O-Brien SG et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N. Engl. J. Med. 355, 2408–2417 (2006).
  • Dewald G, Wyatt W, Juneau A et al. Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. Blood 91((), 3357–3365 (1998).
  • Testoni N, Marzocchi G, Luatti S et al. Chronic myeloid leukemia: a prospective comparison of interphase fluorescence in situ hybridization and chromosome banding analysis for the definition of complete cytogenetic response: a study of the GIMEMA CML WP. Blood 114(24), 4939–4943 (2009).
  • Tkachuk D, Westbrook C, Andreeff M et al. Detection of BCR–ABL fusion in chronic myelogeneous leukemia by in situ hybridization. Science 250, 559–562 (1990).
  • Dewald G, Schad C, Christensen E et al. The application of fluorescent in situ hybridization to detect MBCR/ABL fusion in variant Ph chromosomes in CML and ALL. Cancer Genet. Cytogenet. 71(1), 7–14 (1993).
  • Chase A, Grand F, Zhang J et al. Factors influencing the false positive and negative rates of BCR–ABL fluorescence in situ hybridization. Genes Chromosomes Cancer 18, 246–253 (1997).
  • Primo D, Tabernero M, Rasillo A et al. Patterns of BCR/ABL gene rearrangements by interphase fluorescence in situ hybridization (FISH) in BCR/ABL+ leukemias: incidence and underlying genetic abnormalities. Leukemia 17, 1124–1129 (2003).
  • Herens C, Tassin F, Lemaire V et al. Deletion of the 5’-ABL region: a recurrent anomaly detected by fluorescence in situ hybridization in about 10% of Philadelphia-positive chronic myeloid leukaemia patients. Br. J. Haematol. 110, 214–216 (2000).
  • Sinclair P, Nacheva E, Leversha M et al. Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood 95(3), 738–744 (2000).
  • Sinclair P, Green A, Grace C et al. Improved sensitivity of BCR–ABL detection: a triple-probe three-color fluorescence in situ hybridization system. Blood 90(4), 1395–1402 (1997).
  • Buno I, Wyatt W, Zinsmeister A et al. A special fluorescent in situ hybridization technique to study peripheral blood and assess the effectiveness of interferon therapy in chornic myeloid leukemia. Blood 92(7), 2315–2321 (1998).
  • Dewald G, Wyatt W, Silver R. Atypical BCR and ABL D-FISH patterns in chronic myeloid leukemia and their possible role in therapy. Leuk. Lymphoma 34(5–6), 481–491 (1999).
  • Faderl S, Hochhaus A, Hughes T. Monitoring of minimal residual disease in chronic myeloid leukemia. Hematol. Oncol. Clin. N. Am. 18(3), 657–670 (2004).
  • Press RD, Love Z, Tronnes AA et al. BCR–ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML. Blood 107(11), 4250–4256 (2006).
  • Branford S, Seymour JF, Grigg A et al. BCR–ABL messenger RNA levels continue to decline in patients with chronic phase myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR–ABL using strict sensitivity criteria. Clin. Cancer. Res. 13(23), 7080–7085 (2007).
  • Press RD, Galderisi C, Yang R et al. A half-log increase in BCR–ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response. Clin. Cancer. Res. 13(20), 6136–6143 (2007).
  • Luu M, Rempfer C, Press RD. In CML patients treated with tyrosine kinase inhibitors, BCR–ABL PCR negativity after 18 months of therapy, compared to major molecular response, portends a superior progression free survival [abstract]. J. Mol. Diag. 14(6), 658 (2012).
  • Radich JP. How I monitor residual disease in chronic myeloid leukemia. Blood 114(16), 3376–3381 (2009).
  • Hughes T, Brandford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukemia. Blood Rev. 20(1), 29–41 (2006).
  • Quintas-Cardama A, Kantarjian H, Jones D et al. Delayed achievement of cytogenetic and molecular response is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving high-dose or standard-dose imatinib therapy. Blood 113(25), 6315–6321 (2009).
  • Marin D, Ibrahim AR, Lucas C et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J. Clin. Oncol. 30(3), 232–238 (2012).
  • Hughes T, Hochhaus A, Brandford S et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood 116(19), 3758–3765 (2010).
  • Brandford S, Fletcher L, Cross NC et al. Desirable performance characteristics for BCR–ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. Blood 112(8), 3330–3338 (2008).
  • White HE, Matejtschuk P, Rigsby P et al. Establishment of the first World Health Organization International Genetic Reference Panel for quantitation of BCR–ABL mRNA. Blood 116(22), e111–e117 (2010).
  • Press RD, Willis SG, Laudadio J et al. Determining the rise in BCR–ABL RNA that optimally predicts a kinase domain mutation in patients with chronic myeloid leukemia on imatinib. Blood 114(13), 2598–2605 (2009).
  • Branford S, Rudzki Z, Parkinson I et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR–ABL kinase domain mutations. Blood 104(9), 2926–2932 (2004).
  • Wang L, Knight K, Lucas C et al. The role of serial BCR–ABL transcript monitoring in predicting the emergence of BCR–ABL kinase mutations in imatinib-treated patients with chronic myeloid leukemia. Haematologica 91(2), 235–239 (2006).
  • Jabbour E, Kantarjian H, Jones D. Frequency and clinical significance of BCR–ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia 20(10), 1767–1773 (2006).
  • Baccarani M, Cortes J, Pane F et al. Chronic myeloid leukemia: An update of concepts and management recommendations of European LeukemiaNet. J. Clin. Oncol. 27(35), 6041–6051 (2009).
  • Branford S, Rudski Z, Walsh S et al. Detection of BCR–ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 102(1), 276–283 (2003).
  • Khorashad JS, de Lavallade H, Apperley JF et al. Finding kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression. J. Clin. Oncol. 26(29), 4806–4813 (2008).
  • Soverini S, Martinelli G, Rosti G et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J. Clin. Oncol. 23(18), 4100–4109 (2005).
  • Laudadio J, Deininger MW, Mauro MJ et al. an intron-derived insertion/truncation in the BCR–ABL kinase domain in chronic myeloid leukemia patients undergoing kinase inhibitor therapy. J. Mol. Diag. 10(2), 177–180 (2008).
  • Khorashad JS, Anand M, Marin D et al. The presence of a BCR–ABL mutant allele in CML does not always explain clinical resistance to imatinib. Leukemia 20(4), 658–663 (2006).
  • Willis S, Lange T, Demehri S et al. High sensitivity of BCR–ABL kinase domain mutations in imatinib-naïve pataients: correlation with clonal cytogenetic evolution but not response to therapy. Blood 106(6), 2128–2137 (2005).
  • Sherbenou DW, Wong MJ, Humayun A et al. Mutations of the BCR–ABL kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib. Leukemia 21(3), 489–493 (2007).
  • Trausen A, Pacheco JM, Luzzatto L et al. Somatic mutations and the hierarchy of hematopoiesis. Bioessay 32(11), 1003–1008 (2010).
  • Shah NP, Nicoll JM, Nagar B 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 Cell 2(2), 117–125 (2002).
  • Soverini S, Colarossi S, Gnani A et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin. Cancer Res. 12(24), 7374–7379 (2006).
  • Gorre ME, Mohammed M, Ellwood K et al. Clinical resistance to STI-571 cancer therapy caused by BCR–ABL gene mutation or amplification. Science 293(5531), 876–880 (2001).
  • Hochhaus A, Kreil S, Corbin AS et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 16(11), 2190–2196 (2002).
  • Laneuville P, Di Lea C, Yin O et al. Comparative in vitro cellular data alone are insufficient to predict clinical responses and guide the choice of BCR–ABL inhibitor for treating imatinib-resistant chronic myeloid leukemia. J. Clin. Oncol. 28(11), e169–e171 (2010).
  • Cortes JE, Kantarjian H, Shah NP et al. Ponatinib in refractory Philadelphia chromosome positive leukemias. N. Engl. J. Med. 367(22), 2075–2088 (2012).
  • O’Hare T, Walters D, Stoffregen E et al. In vitro activity of BCR–ABL inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant ABL kinase domain mutants. Cancer Res. 65(11), 4500–4505 (2005).
  • Weisberg E, Manley P, Mestan J et al. AMN107 (nilotinib): a novel and selective inhibitor of BCR–ABL. Br. J. Cancer 94(12), 1765–1769 (2006).
  • Bradeen H, Eide C, O’Hare T et al. Comparison of imatinib mesylate, dasatinib (BMS-354825) and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations. Blood 108(7), 2332–2338 (2006).
  • Hughes T, Saglio G, Branford S et al. Impact of baseline BCR–ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J. Clin. Oncol. 27(25), 4204–4210 (2009).
  • Muller MC, Cortes JE, Kim DW et al. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR–ABL mutations. Blood 114(24), 4944–4953 (2009).
  • Soverini S, Martinelli G, Colarossi S et al. Presence or the emergence of a F317L BCR–ABL mutation may be associated with resistance to dasatinib in Philadelphia chromosome-positive leukemia. J. Clin. Oncol. 24(33): e51–e52, (2006).
  • Soverini S, Martinelli G, Colarossi S et al. Second-line treatment with dasatinib in patients resistant to imatinib can select novel inhibitor-specific BCR–ABL mutants in Ph+ ALL. Lancet Oncol. 8(3), 273–274 (2007).
  • Cortes J, Jabbour E, Kantarjian H et al. Dynamics of BCR–ABL kinase domain mutations in chronic myeloid leukemia after sequential treatment with multiple tyrosine kinase inhibitors. Blood 110(12), 4005–4011 (2007).
  • Khorashad JS, Milojkovic D, Mehta P et al. In vivo kinetics of kinase domain mutations in CML patients treated with dasatinib after failing imatinib. Blood 111(4), 2378–2381 (2008).
  • Jabbour E, Jones D, Kantarjian HM et al. Long-term outcome of patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR–ABL kinase domain mutations. Blood 114(10), 2037–2043 (2009).
  • Crossman LC, O’Hare T, Lange T et al. A single nucleotide polymorphism in the coding region of ABL and its effects on sensitivity to imatinib. Leukemia 19(11), 1859–1862 (2005).
  • Nicolini FE, Chabane K, Cayuela JM et al. The role of the K247R substitution in the ABL tyrosine kinase domain in sensitivity to imatinib. Haematologica 91(1), 137–138 (2006).
  • Ernst T, Hoffman J, Erben P et al. ABL single nucleotide polymorphisms may masquerade as BCR–ABL mutations associated with resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia. Haematologica 93(9), 1389–1393 (2008).
  • Soverini S, Hochhaus A, Nicolini FE et al. BCR–ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood 118(5), 1208–1215 (2011).

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