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Array Comparative Genomic Hybridization pp 55–68Cite as

Application of Array Comparative Genomic Hybridization in Chronic Myeloid Leukemia

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 973))

Abstract

Chromosomal alteration is one of the hallmarks of chronic myeloid leukemia (CML), and the Philadelphia chromosome is the most important and key example of the chromosomal changes in this disease. Indeed, the BCR–ABL1 fusion product is a target against which many tyrosine kinase inhibitors (TKIs) have been proven to be effective in the treatment of CML. However, the reality is that CML patients show resistance to TKIs both in an acquired and de novo manner, and the mechanism of TKI resistance is still largely unknown. This phenomenon suggests that in addition to the BCR–ABL mutation, further genetic alterations such as copy number aberration may be involved in unexplained TKI resistance. Although the recent array comparative genomic hybridization analyses (array-CGH) across the whole genome have detected multiple genetic aberrations in CML, the detailed feature of chromosomal alterations involved in different clinical phases of CML, such as chronic phase, accelerated phase, and blast crisis, remains unclear. Here we review the methodological aspects of array-CGH analysis for studying CML and its related data analysis.

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References

  1. Nowell PC, Hungerford DA (1961) Chromosome studies in human leukemia. II. Chronic granulocytic leukemia. J Natl Cancer Inst 27:1013–1035

    PubMed  CAS  Google Scholar 

  2. Faderl S, Talpaz M, Estrov Z et al (1999) The biology of chronic myeloid leukemia. N Engl J Med 341(3):164–172. doi:10.1056/NEJM199907153410306

    Article  PubMed  CAS  Google Scholar 

  3. Vigil CE, Griffiths EA, Wang ES et al (2011) Interpretation of cytogenetic and molecular results in patients treated for CML. Blood Rev 25(3):139–146. doi:S0268-960X(11)00019-1 [pii]10.1016/j. blre. 011.02.001

    Article  PubMed  CAS  Google Scholar 

  4. Quintas-Cardama A, Cortes J (2009) Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood 113(8):1619–1630. doi:blood-2008-03-144790 [pii] 10. 1182/blood-2008-03-144790

    Article  PubMed  CAS  Google Scholar 

  5. Baccarani M, Saglio G, Goldman J et al (2006) Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the european leukemianet. Blood 108(6):1809–1820. doi:blood-2006-02-005686 [pii] 10. 1182/blood-2006-02-005686

    Article  PubMed  CAS  Google Scholar 

  6. O’brien SG, Guilhot F, Larson RA et al (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348(11):994–1004. doi:10. 1056/NEJMoa022457 348/11/994 [pii]

    Article  PubMed  Google Scholar 

  7. Diamond JM, Melo JV (2011) Mechanisms of resistance to BCR-ABL kinase inhibitors. Leuk Lymphoma 52(Suppl 1):12–22. doi:10. 3109/10428194. 2010. 546920

    Article  PubMed  CAS  Google Scholar 

  8. Chu S, Xu H, Shah NP et al (2005) Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment. Blood 105(5):2093–2098. doi:10. 1182/blood-2004-03-1114 2004-03-1114 [pii]

    Article  PubMed  CAS  Google Scholar 

  9. Corbin AS, La Rosee P, Stoffregen EP et al (2003) Several BCR-ABL kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood 101(11):4611–4614. doi:10. 1182/blood-2002-12-3659 2002-12-3659 [pii]

    Article  PubMed  CAS  Google Scholar 

  10. Morel F, Bris MJ, Herry A et al (2003) Double minutes containing amplified bcr-abl fusion gene in a case of chronic myeloid leukemia treated by imatinib. Eur J Haematol 70(4):235–239. doi:046 [pii]

    Article  PubMed  Google Scholar 

  11. Azam M, Latek RR, Daley GQ (2003) Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 112(6):831–843. doi:S0092867403001909 [pii]

    Article  PubMed  CAS  Google Scholar 

  12. Kantarjian HM, Talpaz M, O’brien S et al (2003) Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood 101(2):473–475. doi:10. 1182/blood-2002-05-1451 2002-05-1451 [pii]

    Article  PubMed  CAS  Google Scholar 

  13. Kantarjian HM, Larson RA, Guilhot F et al (2009) Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase. Cancer 115(3):551–560. doi:10. 1002/cncr. 24066

    Article  PubMed  CAS  Google Scholar 

  14. Koh Y, Kim I, Yoon SS et al (2010) Phase IV study evaluating efficacy of escalated dose of imatinib in chronic myeloid leukemia patients showing suboptimal response to standard dose imatinib. Ann Hematol. doi:10. 1007/s00277-010-0910-8

    Google Scholar 

  15. Jabbour E, Cortes JE, Kantarjian HM (2009) Suboptimal response to or failure of imatinib treatment for chronic myeloid leukemia: what is the optimal strategy? Mayo Clin Proc 84(2):161–169. doi:84/2/161 [pii] 10. 4065/84. 2. 161

    Article  PubMed  Google Scholar 

  16. Lee TS, Potts SJ, Kantarjian H et al (2008) Molecular basis explanation for imatinib resistance of BCR-ABL due to T315I and P-loop mutations from molecular dynamics simulations. Cancer 112(8):1744–1753. doi:10. 1002/cncr. 23355

    Article  PubMed  CAS  Google Scholar 

  17. Kallioniemi A, Kallioniemi OP, Sudar D et al (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258(5083):818–821

    Article  PubMed  CAS  Google Scholar 

  18. Knuutila S, Aalto Y, Autio K et al (1999) DNA copy number losses in human neoplasms. Am J Pathol 155(3):683–694. doi:S0002-9440(10)65166-8 [pii] 10. 1016/S0002-9440(10)65166-8

    Article  PubMed  CAS  Google Scholar 

  19. Lee C, Rens W, Yang F (2001) Multicolor fluorescence in situ hybridization (fish) approaches for simultaneous analysis of the entire human genome. Curr Protoc Hum Genet. doi:10. 1002/0471142905. hg0409s24, Chapter 4:Unit4. 9

    Google Scholar 

  20. Pinkel D, Segraves R, Sudar D et al (1998) High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 20(2):207–211. doi:10. 1038/2524

    Article  PubMed  CAS  Google Scholar 

  21. Albertson DG, Pinkel D (2003) Genomic microarrays in human genetic disease and cancer. Hum Mol Genet 12(Spec No 2):R145–R152. doi:10. 1093/hmg/ddg261 ddg261 [pii]

    Article  PubMed  CAS  Google Scholar 

  22. Lockwood WW, Chari R, Chi B, et al (2006) Recent advances in array comparative genomic hybridization technologies and their appli­cations in human genetics. Eur J Hum Genet 14:139–48. doi:10.1038/sj.ejhg.5201531

    Article  PubMed  Google Scholar 

  23. Kallioniemi A (2008) CGH microarrays and cancer. Curr Opin Biotechnol 19(1):36–40. doi:S0958-1669(07)00148-6 [pii] 10. 1016/j. copbio. 2007. 11. 004

    Article  PubMed  CAS  Google Scholar 

  24. Shinawi M, Cheung SW (2008) The array CGH and its clinical applications. Drug Discov Today 13(17–18):760–770. doi:S1359-6446(08)00220-1 [pii] 10. 1016/j. drudis. 2008. 06. 007

    Article  PubMed  CAS  Google Scholar 

  25. Maciejewski JP, Tiu RV, O’keefe C (2009) Application of array-based whole genome scanning technologies as a cytogenetic tool in haematological malignancies. Br J Haematol 146(5):479–488. doi:BJH7757 [pii] 10. 1111/j. 1365-2141. 2009. 07757. x

    Article  PubMed  CAS  Google Scholar 

  26. Kim MY, Yim SH, Kwon MS et al (2006) Recurrent genomic alterations with impact on survival in colorectal cancer identified by genome-wide array comparative genomic hybridization. Gastroenterology 131(6):1913–1924. doi:S0016-5085(06)02255-4 [pii] 10. 1053/j. gastro. 2006. 10. 021

    Article  PubMed  CAS  Google Scholar 

  27. Kim TM, Yim SH, Lee JS et al (2005) Genome-wide screening of genomic alterations and their clinicopathologic implications in non-small cell lung cancers. Clin Cancer Res 11(23):8235–8242. doi:11/23/8235 [pii] 10. 1158/1078-0432. CCR-05-1157

    Article  PubMed  CAS  Google Scholar 

  28. Kim TM, Yim SH, Shin SH et al (2008) Clinical implication of recurrent copy number alterations in hepatocellular carcinoma and putative oncogenes in recurrent gains on 1q. Int J Cancer 123(12):2808–2815. doi:10. 1002/ijc. 23901

    Article  PubMed  CAS  Google Scholar 

  29. Koh Y, Kim DY, Park SH et al (2010) GSTT1 copy number gain is a poor predictive marker for escalated-dose imatinib treatment in chronic myeloid leukemia: genetic predictive marker found using array comparative genomic hybridization. Cancer Genet Cytogenet 203(2):215–221. doi:S0165-4608(10)00485-1 [pii] 10. 1016/j. cancergencyto. 2010. 08. 022

    Article  PubMed  CAS  Google Scholar 

  30. La Rosee P, Hochhaus A (2010) Molecular pathogenesis of tyrosine kinase resistance in chronic myeloid leukemia. Curr Opin Hematol 17(2):91–96. doi:10. 1097/MOH. 0b013e32­83366be1

    Article  PubMed  Google Scholar 

  31. Willis SG, Lange T, Demehri S et al (2005) High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy. Blood 106(6):2128–2137. doi:2005-03-1036 [pii] 10. 1182/blood-2005-03-1036

    Article  PubMed  CAS  Google Scholar 

  32. Thomas J, Wang L, Clark RE et al (2004) Active transport of imatinib into and out of cells: implications for drug resistance. Blood 104(12):3739–3745. doi:10. 1182/blood-2003-12-4276 2003-12-4276 [pii]

    Article  PubMed  CAS  Google Scholar 

  33. Mahon FX, Belloc F, Lagarde V et al (2003) MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 101(6):2368–2373. doi:10. 1182/blood. V101. 6. 2368 101/6/2368 [pii]

    Article  PubMed  CAS  Google Scholar 

  34. Donato NJ, Wu JY, Stapley J et al (2003) BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 101(2):690–698. doi:10. 1182/blood. V101. 2. 690 101/2/690 [pii]

    Article  PubMed  CAS  Google Scholar 

  35. Griswold IJ, Macpartlin M, Bumm T et al (2006) Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib. Mol Cell Biol 26(16):6082–6093. doi:26/16/6082 [pii] 10. 1128/MCB. 02202-05

    Article  PubMed  CAS  Google Scholar 

  36. Soverini S, Martinelli G, Rosti G et al (2005) 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. doi:JCO. 2005. 05. 531 [pii] 10. 1200/JCO. 2005. 05. 531

    Article  PubMed  CAS  Google Scholar 

  37. Khorashad JS, De Lavallade H, Apperley JF et al (2008) Finding of 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. doi:JCO. 2008. 16. 9953 [pii] 10. 1200/JCO. 2008. 16. 9953

    Article  PubMed  CAS  Google Scholar 

  38. Skorski T (2011) Chronic myeloid leukemia cells refractory/resistant to tyrosine kinase inhibitors are genetically unstable and may cause relapse and malignant progression to the terminal disease state. Leuk Lymphoma 52(Suppl 1):23–29. doi:10. 3109/10428194. 2010. 546912

    Article  PubMed  CAS  Google Scholar 

  39. Koptyra M, Cramer K, Slupianek A et al (2008) BCR/ABL promotes accumulation of chromosomal aberrations induced by oxidative and genotoxic stress. Leukemia 22(10):1969–1972. doi:leu200878 [pii] 10. 1038/leu. 2008. 78

    Article  PubMed  CAS  Google Scholar 

  40. Dierov J, Sanchez PV, Burke BA et al (2009) BCR/ABL induces chromosomal instability after genotoxic stress and alters the cell death threshold. Leukemia 23(2):279–286. doi:leu2008308 [pii] 10. 1038/leu. 2008. 308

    Article  PubMed  CAS  Google Scholar 

  41. Brazma D, Grace C, Howard J et al (2007) Genomic profile of chronic myelogenous ­leukemia: imbalances associated with disease progression. Genes Chromosomes Cancer 46(11):1039–1050. doi:10. 1002/gcc. 20487

    Article  PubMed  CAS  Google Scholar 

  42. Khorashad JS, De Melo VA, Fiegler H et al (2008) Multiple sub-microscopic genomic lesions are a universal feature of chronic myeloid leukaemia at diagnosis. Leukemia 22(9):1806–1807. doi:leu2008210 [pii] 10. 1038/leu. 2008. 210

    Article  PubMed  CAS  Google Scholar 

  43. Nadarajan VS, Phan CL, Ang CH et al (2011) Identification of copy number alterations by array comparative genomic hybridization in patients with late chronic or accelerated phase chronic myeloid leukemia treated with imatinib mesylate. Int J Hematol 93(4):465–473. doi:10. 1007/s12185-011-0796-9

    Article  PubMed  CAS  Google Scholar 

  44. Nacheva EP, Brazma D, Virgili A et al (2010) Deletions of immunoglobulin heavy chain and T cell receptor gene regions are uniquely associated with lymphoid blast transformation of chronic myeloid leukemia. BMC Genomics 11:41. doi:1471-2164-11-41 [pii] 10. 1186/1471-2164-11-41

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by grants from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (0405-BC02-0604-0004)(A040002).

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Authors and Affiliations

  1. Department of Internal Medicine, Diagnostic DNA Chip Center, Seoul National University College of Medicine, Seoul, South Korea

    Seonyang Park & Youngil Koh

  2. Department of Internal Medicine, Diagnostic DNA Chip Center, Seoul National University College of Medicine, Seoul, Korea

    Seung-Hyun Jung & Yeun-Jun Chung

Authors
  1. Seonyang Park
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  2. Youngil Koh
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  3. Seung-Hyun Jung
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  4. Yeun-Jun Chung
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Corresponding author

Correspondence to Seonyang Park .

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Editors and Affiliations

  1. , Dept. of Pathology & Lab. Medicine, The Ottawa Hospital, Smyth Road 501, Ottawa, K1H 8L6, Ontario, Canada

    Diponkar Banerjee

  2. , Dept. of Molecular Oncology, BC Cancer Agency, West 10th Avenue 675, Vancouver, V5T 4E6, British Columbia, Canada

    Sohrab P. Shah

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Park, S., Koh, Y., Jung, SH., Chung, YJ. (2013). Application of Array Comparative Genomic Hybridization in Chronic Myeloid Leukemia. In: Banerjee, D., Shah, S. (eds) Array Comparative Genomic Hybridization. Methods in Molecular Biology, vol 973. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-281-0_4

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  • DOI: https://doi.org/10.1007/978-1-62703-281-0_4

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  • Publisher Name: Humana Press, Totowa, NJ

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