Advertisement

Molecular Techniques Used in the Evaluation of Pediatric Acute Leukemia

  • Zeba N. SinghEmail author
  • Margaret L. Gulley
Chapter
  • 818 Downloads
Part of the Molecular and Translational Medicine book series (MOLEMED)

Abstract

Rapid proliferation of a plethora of molecular techniques has made it possible to evaluate the entire genome of the leukemic cell. The WHO classification scheme for hematolymphoid neoplasms (WHO classification of tumours of haematopoietic and lymphoid tissue (IARC WHO classification of tumours), 2008) and the management guidelines of the National Comprehensive Cancer Network (NCCN clinical practice guideleines in oncology TM. Acute Myeloid Leukemia, 2011) highlight the importance of genetic tests in diagnosis, treatment planning, and follow-up of acute leukemia. This chapter introduces the progressive development of the different molecular methods relevant in the evaluation of acute leukemia. The basic principles are discussed. The technical details of tests are beyond the scope of this chapter. These techniques are similarly applicable for the evaluation of other hematolymphoid neoplasms including lymphoma, myeloproliferative disorders, and myelodysplasia.

Keywords

Cytogenetic aberrations Fluorescent in situ hybridization Minimal residual disease Polymerase chain reaction Comparative genomic hybridization 

References

  1. 1.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissue (IARC WHO classification of tumours). 4th ed. Lyon, France: IARC press; 2008.Google Scholar
  2. 2.
    O’Donnell MR, Abboud CN, Altman J, Appelbaum FR, Arber DA, Coutre SE, et al. NCCN clinical practice guidelines in oncology TM. Acute Myeloid Leukemia. (2011). http://www.nccn.org/professionals/physician_gls/f_guidelines.asp
  3. 3.
    Vorsanova SG, Yurov YB, Iourov IY. Human interphase chromosomes: a review of available molecular cytogenetic technologies. Mol Cytogenet. 2010;3:1–15.PubMedGoogle Scholar
  4. 4.
    Harrison CJ, Haas O, Harbott J, Biondi A, Stanulla M, Trka J, et al. Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the biology and diagnosis committee of the international Berlin-Frankfurt-Munster study group. Br J Haematol. 2010;151(2):132–42.PubMedGoogle Scholar
  5. 5.
    Hasle H, Alonzo TA, Auvrignon A, Behar C, Chang M, Creutzig U, et al. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood. 2007;109(11):4641–7.PubMedGoogle Scholar
  6. 6.
    Manola KN. Cytogenetics of pediatric acute myeloid leukemia. Eur J Haematol. 2009; 83(5):391–405.PubMedGoogle Scholar
  7. 7.
    Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the medical research council (MRC) UKALLXII/Eastern cooperative oncology group (ECOG) 2993 trial. Blood. 2007; 109 (8):3189–97.PubMedGoogle Scholar
  8. 8.
    Breems DA, Van Putten WL, De Greef GE, Van Zelderen-Bhola SL, Gerssen-Schoorl KB, Mellink CH, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26(29):4791–7.PubMedGoogle Scholar
  9. 9.
    Lange BJ, Smith FO, Feusner J, Barnard DR, Dinndorf P, Feig S, et al. Outcomes in CCG-2961, a children’s oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children’s oncology group. Blood. 2008;111(3):1044–53.PubMedGoogle Scholar
  10. 10.
    Shaffer LG, Slovak ML, Campbell LJ, editors. ISCN 2009: An International System for Human Cytogenetic Nomenclature (2009): recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. 1st ed. Switzerland: S Karger AG; 2009.Google Scholar
  11. 11.
    Douet-Guilbert N, Morel F, Le Bris MJ, Herry A, Le Calvez G, Marion V, et al. A fluorescence in situ hybridization study of TEL-AML1 fusion gene in B-cell acute lymphoblastic leukemia (1984–2001). Cancer Genet Cytogenet. 2003;144(2):143–7.PubMedGoogle Scholar
  12. 12.
    Mathew S, Shurtleff SA, Raimondi SC. Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AML1) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2001;32(2): 188–93.PubMedGoogle Scholar
  13. 13.
    Nordgren A, Heyman M, Sahlen S, Schoumans J, Soderhall S, Nordenskjold M, et al. Spectral karyotyping and interphase FISH reveal abnormalities not detected by conventional G-banding. Implications for treatment stratification of childhood acute lymphoblastic leukaemia: detailed analysis of 70 cases. Eur J Haematol. 2002;68(1):31–41.PubMedGoogle Scholar
  14. 14.
    Schichman SA, Caligiuri MA, Gu Y, Strout MP, Canaani E, Bloomfield CD, et al. ALL-1 partial duplication in acute leukemia. Proc Natl Acad Sci USA. 1994;91:6236–9.PubMedGoogle Scholar
  15. 15.
    Graux C, Cools J, Michaux L, Vandenberghe P, Hagemeijer A. Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia. 2006;20(9):1496–510.PubMedGoogle Scholar
  16. 16.
    Kearney L. Molecular cytogenetics. Best Pract Res Clin Haematol. 2001;14:645–68.PubMedGoogle Scholar
  17. 17.
    Robinson HM, Martineau M, Harris RL, Barber KE, Jalali GR, Moorman AV, et al. Derivative chromosome 9 deletions are a significant feature of childhood Philadelphia chromosome positive acute lymphoblastic leukaemia. Leukemia. 2005;19(4):564–71.PubMedGoogle Scholar
  18. 18.
    Poppe B, Cauwelier B, Van Limbergen H, Yigit N, Philippe J, Verhasselt B, et al. Novel cryptic chromosomal rearrangements in childhood acute lymphoblastic leukemia detected by multiple color fluorescent in situ hybridization. Haematologica. 2005;90(9):1179–85.PubMedGoogle Scholar
  19. 19.
    Moorman AV, Clark R, Farrell DM, Hawkins JM, Martineau M, Secker-Walker LM. Probes for hidden hyperdiploidy in acute lymphoblastic leukaemia. Genes Chromosomes Cancer. 1996;16(1):40–5.PubMedGoogle Scholar
  20. 20.
    Stark B, Jeison M, Gobuzov R, Krug H, Glaser-Gabay L, Luria D, et al. Near haploid childhood acute lymphoblastic leukemia masked by hyperdiploid line: detection by fluorescence in situ hybridization. Cancer Genet Cytogenet. 2001;128(2):108–13.PubMedGoogle Scholar
  21. 21.
    Speicher MR, Gwyn Ballard S, Ward DC. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nat Genet. 1996;12(4):368–75.PubMedGoogle Scholar
  22. 22.
    Schrock E, Veldman T, Padilla-Nash H, Ning Y, Spurbeck J, Jalal S, et al. Spectral karyotyping refines cytogenetic diagnostics of constitutional chromosomal abnormalities. Hum Genet. 1997;101(3):255–62.PubMedGoogle Scholar
  23. 23.
    Ried T, Schrock E, Ning Y, Wienberg J. Chromosome painting: a useful art. Hum Mol Genet. 1998;7(10):1619–26.PubMedGoogle Scholar
  24. 24.
    Liehr T, Starke H, Weise A, Lehrer H, Claussen U. Multicolor FISH probe sets and their applications. Histol Histopathol. 2004;19(1):229–37.PubMedGoogle Scholar
  25. 25.
    Verdorfer I. Comparative genomic hybridization-aided unraveling of complex karyotypes in human hematopoietic neoplasms. Cancer Genet Cytogenet. 2001;124:1–6.PubMedGoogle Scholar
  26. 26.
    Kowalczyk JR, Babicz M, Gaworczyk A, Lejman M, Winnicka D, Styka B, et al. Structural and numerical abnormalities resolved in one-step analysis: the most common chromosomal rearrangements detected by comparative genomic hybridization in childhood acute lymphoblastic leukemia. Cancer Genet Cytogenet. 2010;200(2):161–6.PubMedGoogle Scholar
  27. 27.
    Larsen J, Ottesen AM, Kirchhoff M, Lundsteen C, Larsen JK. High resolution comparative genomic hybridization detects 7–8 megabasepair deletion in PCR amplified DNA. Anal Cell Pathol. 2001;23(2):61–4.PubMedGoogle Scholar
  28. 28.
    Bentz M, Plesch A, Stilgenbauer S, Dohner H, Lichter P. Minimal sizes of deletions detected by comparative genomic hybridization. Genes Chromosomes Cancer. 1998;21(2):172–5.PubMedGoogle Scholar
  29. 29.
    Kirchhoff M, Gerdes T, Maahr J, Rose H, Bentz M, Dohner H, et al. Deletions below 10 megabasepairs are detected in comparative genomic hybridization by standard reference intervals. Genes Chromosomes Cancer. 1999;25(4):410–3.PubMedGoogle Scholar
  30. 30.
    Gebhart E, Verdorfer I, Saul W, Trautmann U, Brecevic L. Delimiting the use of comparative genomic hybridization in human myeloid neoplastic disorders. Int J Oncol. 2000;16(6):1099–105.PubMedGoogle Scholar
  31. 31.
    Coe BP, Ylstra B, Carvalho B, Meijer GA, Macaulay C, Lam WL. Resolving the resolution of array CGH. Genomics. 2007;89(5):647–53.PubMedGoogle Scholar
  32. 32.
    Weiss MM, Hermsen MA, Meijer GA, van Grieken NC, Baak JP, Kuipers EJ, et al. Comparative genomic hybridization. Mol Pathol. 1999;52(5):243–51.PubMedGoogle Scholar
  33. 33.
    Haas O, Henn T, Romanakis K, du Manoir S, Lengauer C. Comparative genomic hybridization as part of a new diagnostic strategy in childhood hyperdiploid acute lymphoblastic leukemia. Leukemia. 1998;12(4):474–81.PubMedGoogle Scholar
  34. 34.
    Jarosova M, Holzerova M, Jedlickova K, Mihal V, Zuna J, Stary J, et al. Importance of using comparative genomic hybridization to improve detection of chromosomal changes in childhood acute lymphoblastic leukemia. Cancer Genet Cytogenet. 2000;123(2):114–22.PubMedGoogle Scholar
  35. 35.
    Karhu R, Siitonen S, Tanner M, Keinanen M, Makipernaa A, Lehtinen M, et al. Genetic aberrations in pediatric acute lymphoblastic leukemia by comparative genomic hybridization. Cancer Genet Cytogenet. 1997;95(2):123–9.PubMedGoogle Scholar
  36. 36.
    Kim MH, Stewart J, Devlin C, Kim YT, Boyd E, Connor M. The application of comparative genomic hybridization as an additional tool in the chromosome analysis of acute myeloid leukemia and myelodysplastic syndromes. Cancer Genet Cytogenet. 2001;126(1):26–33.PubMedGoogle Scholar
  37. 37.
    McGrattan P, Campbell S, Cuthbert R, Jones FG, McMullin MF, Humphreys M. Integration of conventional cytogenetics, comparative genomic hybridisation and interphase fluorescence in situ hybridisation for the detection of genomic rearrangements in acute leukaemia. J Clin Pathol. 2008;61(8):903–8.PubMedGoogle Scholar
  38. 38.
    Rice M, Breen CJ, O’Meara A, Breatnach F, O’Marcaigh AS, Stallings RL. Comparative genomic hybridization in pediatric acute lymphoblastic leukemia. Pediatr Hematol Oncol. 2000;17(2):141–7.PubMedGoogle Scholar
  39. 39.
    Szczepanski T, Harrison CJ, van Dongen JJ. Genetic aberrations in paediatric acute leukaemias and implications for management of patients. Lancet Oncol. 2010;11(9):880–9.PubMedGoogle Scholar
  40. 40.
    van Dongen JJ, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G, et al. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. report of the BIOMED-1 concerted action Investigation of minimal residual disease in acute leukemia. Leukemia. 1999;13(12):1901–28.PubMedGoogle Scholar
  41. 41.
    Chun SM, Kim YL, Choi HB, Oh YT, Kim YJ, Lee S, et al. Identification of leukemia-specific fusion gene transcripts with a novel oligonucleotide array. Mol Diagn Ther. 2007; 11(1):21–8.PubMedGoogle Scholar
  42. 42.
    Pakakasama S, Kajanachumpol S, Kanjanapongkul S, Sirachainan N, Meekaewkunchorn A, Ningsanond V, et al. Simple multiplex RT-PCR for identifying common fusion transcripts in childhood acute leukemia. Int J Lab Hematol. 2008;30(4):286–91.PubMedGoogle Scholar
  43. 43.
    Pihan G. Detection of gene fusions in acute leukemia using bead microarrays. Curr Protoc Cytom. 2006;Chapter 13:Unit13.7.Google Scholar
  44. 44.
    Scurto P, Hsu Rocha M, Kane JR, Williams WK, Haney DM, Conn WP, et al. A multiplex RT-PCR assay for the detection of chimeric transcripts encoded by risk-stratifying translocations of pediatric acute lymphoblastic leukemia. Leukemia. 1998;12(12):1994–2005.PubMedGoogle Scholar
  45. 45.
    Yang YL, Lin SR, Chen JS, Hsiao CC, Lin KH, Sheen JM, et al. Multiplex reverse transcription-polymerase chain reaction as diagnostic molecular screening of 4 common fusion chimeric genes in Taiwanese children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2010;32(8):e23–30.Google Scholar
  46. 46.
    De Braekeleer E, Meyer C, Douet-Guilbert N, Morel F, Le Bris MJ, Berthou C, et al. Complex and cryptic chromosomal rearrangements involving the MLL gene in acute leukemia: a study of 7 patients and review of the literature. Blood Cells Mol Dis. 2010;44(4):268–74.PubMedGoogle Scholar
  47. 47.
    Meyer C, Kowarz E, Hofmann J, Renneville A, Zuna J, Trka J, et al. New insights to the MLL recombinome of acute leukemias. Leukemia. 2009;23(8):1490–9.PubMedGoogle Scholar
  48. 48.
    Thorn I, Botling J, Hermansson M, Lonnerholm G, Sundstrom C, Rosenquist R, et al. Monitoring minimal residual disease with flow cytometry, antigen-receptor gene rearrangements and fusion transcript quantification in Philadelphia-positive childhood acute lymphoblastic leukemia. Leuk Res. 2009;33(8):1047–54.PubMedGoogle Scholar
  49. 49.
    Zaliova M, Fronkova E, Krejcikova K, Muzikova K, Mejstrikova E, Stary J, et al. Quantification of fusion transcript reveals a subgroup with distinct biological properties and predicts relapse in BCR/ABL-positive ALL: implications for residual disease monitoring. Leukemia. 2009;23(5):944–51.PubMedGoogle Scholar
  50. 50.
    Bartley PA, Martin-Harris MH, Budgen BJ, Ross DM, Morley AA. Rapid isolation of translocation breakpoints in chronic myeloid and acute promyelocytic leukaemia. Br J Haematol. 2010;149(2):231–6.PubMedGoogle Scholar
  51. 51.
    Grimwade D, Jovanovic JV, Hills RK, Nugent EA, Patel Y, Flora R, et al. Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol. 2009;27(22):3650–8.PubMedGoogle Scholar
  52. 52.
    Grimwade D, Tallman MS. Should minimal residual disease monitoring be the standard of care for all patients with acute promyelocytic leukemia? Leuk Res. 2011;35(1):3–7.PubMedGoogle Scholar
  53. 53.
    Endo C, Oda M, Nishiuchi R, Seino Y. Persistence of TEL-AML1 transcript in acute lymphoblastic leukemia in long-term remission. Pediatr Int. 2003;45(3):275–80.PubMedGoogle Scholar
  54. 54.
    Ford AM, Fasching K, Panzer-Grumayer ER, Koenig M, Haas OA, Greaves MF. Origins of “late” relapse in childhood acute lymphoblastic leukemia with TEL-AML1 fusion genes. Blood. 2001;98(3):558–64.PubMedGoogle Scholar
  55. 55.
    Campana D. Progress of minimal residual disease studies in childhood acute leukemia. Curr Hematol Malig Rep. 2010;5(3):169–76.PubMedGoogle Scholar
  56. 56.
    Stow P, Key L, Chen X, Pan Q, Neale GA, Coustan-Smith E, et al. Clinical significance of low levels of minimal residual disease at the end of remission induction therapy in childhood acute lymphoblastic leukemia. Blood. 2010;115(23):4657–63.PubMedGoogle Scholar
  57. 57.
    Basso G, Veltroni M, Valsecchi MG, Dworzak MN, Ratei R, Silvestri D, et al. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol. 2009;27(31):5168–74.PubMedGoogle Scholar
  58. 58.
    de Souza FT, Ornellas MH, Otero de Carvalho L, Tabak D, Abdelhay E. Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia. Leuk Res. 2000;24(10):839–48.Google Scholar
  59. 59.
    Luria D, Rosenthal E, Steinberg D, Kodman Y, Safanaiev M, Amariglio N, et al., The Israel National Study Group of Childhood ALL. Prospective comparison of two flow cytometry methodologies for monitoring minimal residual disease in a multicenter treatment protocol of childhood acute lymphoblastic leukemia. Cytometry B Clin Cytom. 2010;78(6):365–71.Google Scholar
  60. 60.
    Malec M, van der Velden VH, Bjorklund E, Wijkhuijs JM, Soderhall S, Mazur J, et al. Analysis of minimal residual disease in childhood acute lymphoblastic leukemia: comparison between RQ-PCR analysis of Ig/TcR gene rearrangements and multicolor flow cytometric immunophenotyping. Leukemia. 2004;18(10):1630–6.PubMedGoogle Scholar
  61. 61.
    Kitchingman GR, Rovigatti U, Mauer AM, Melvin S, Murphy SB, Stass S. Rearrangement of immunoglobulin heavy chain genes in T cell acute lymphoblastic leukemia. Blood. 1985; 65(3):725–9.PubMedGoogle Scholar
  62. 62.
    Dyer MJ, Akasaka T, Capasso M, Dusanjh P, Lee YF, Karran EL, et al. Immunoglobulin heavy chain locus chromosomal translocations in B-cell precursor acute lymphoblastic leukemia: rare clinical curios or potent genetic drivers? Blood. 2010;115(8):1490–9.PubMedGoogle Scholar
  63. 63.
    Felix CA, Reaman GH, Korsmeyer SJ, Hollis GF, Dinndorf PA, Wright JJ, et al. Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy. Blood. 1987;70(2):536–41.PubMedGoogle Scholar
  64. 64.
    Fey MF, Tobler A, Stadelmann B, Hirt A, Theilkas L, Khandjian EW, et al. Immunogenotyping with antigen receptor gene probes as a diagnostic tool in childhood acute lymphoblastic leukaemia. Eur J Haematol. 1990;45(4):215–22.PubMedGoogle Scholar
  65. 65.
    Meleshko AN, Belevtsev MV, Savitskaja TV, Potapnev MP. The incidence of T-cell receptor gene rearrangements in childhood B-lineage acute lymphoblastic leukemia is related to immunophenotype and fusion oncogene expression. Leuk Res. 2006;30(7):795–800.PubMedGoogle Scholar
  66. 66.
    Szczepański T, Beishuizen A, Pongers-Willemse MJ, Hählen K, Van Wering ER, Wijkhuijs AJ, et al. Cross-lineage T cell receptor gene rearrangements occur in more than ninety percent of childhood precursor-B acute lymphoblastic leukemias: alternative PCR targets for detection of minimal residual disease. Leukemia. 1999;13(2):196–205.PubMedGoogle Scholar
  67. 67.
    van Dongen JJ, Wolvers-Tettero IL. Analysis of immunoglobulin and T cell receptor genes. Part II: possibilities and limitations in the diagnosis and management of lymphoproliferative diseases and related disorders. Clin Chim Acta. 1991;198(1–2):93–174.PubMedGoogle Scholar
  68. 68.
    Cheng GY, Minden MD, Toyonaga B, Mak TW, McCulloch EA. T cell receptor and immunoglobulin gene rearrangements in acute myeloblastic leukemia. J Exp Med. 1986; 163(2):414–24.PubMedGoogle Scholar
  69. 69.
    Kode J, Dudhal N, Banavali S, Advani S, Chiplunkar S. Clonal T-cell receptor gamma and delta gene rearrangements in T-cell acute lymphoblastic leukemia at diagnosis: predictor of prognosis and response to chemotherapy. Leuk Lymphoma. 2004;45(1):125–33.PubMedGoogle Scholar
  70. 70.
    Meleshko AN, Lipay NV, Stasevich IV, Potapnev MP. Rearrangements of IgH, TCRD and TCRG genes as clonality marker of childhood acute lymphoblastic leukemia. Exp Oncol. 2005;27(4):319–24.PubMedGoogle Scholar
  71. 71.
    Szczepanski T, Willemse MJ, Brinkhof B, van Wering ER, van der Burg M, van Dongen JJ. Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at relapse of childhood precursor-B-ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease. Blood. 2002;99(7):2315–23.PubMedGoogle Scholar
  72. 72.
    van der Velden VH, Bruggemann M, Hoogeveen PG, de Bie M, Hart PG, Raff T, et al. TCRB gene rearrangements in childhood and adult precursor-B-ALL: frequency, applicability as MRD-PCR target, and stability between diagnosis and relapse. Leukemia. 2004;18(12):1971–80.PubMedGoogle Scholar
  73. 73.
    Pongers-Willemse MJ, Verhagen OJ, Tibbe GJ, Wijkhuijs AJ, de Haas V, Roovers E, et al. Real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia using junctional region specific TaqMan probes. Leukemia. 1998;12(12):2006–14.PubMedGoogle Scholar
  74. 74.
    Pongers-Willemse MJ, Seriu T, Stolz F, d’Aniello E, Gameiro P, Pisa P, et al. Primers and protocols for standardized detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets: report of the BIOMED-1 CONCERTED ACTION: investigation of minimal residual disease in acute leukemia. Leukemia. 1999;13(1):110–8.PubMedGoogle Scholar
  75. 75.
    Szczepański T, Orfao A, van der Velden VH, San Miguel JF, Van Dongen JJ. Minimal residual disease in leukaemia patients. Lancet Oncol. 2001;2(7):409–17.PubMedGoogle Scholar
  76. 76.
    Beishuizen A, Verhoeven MA, van Wering ER, Hahlen K, Hooijkaas H, van Dongen JJ. Analysis of ig and T-cell receptor genes in 40 childhood acute lymphoblastic leukemias at diagnosis and subsequent relapse: implications for the detection of minimal residual disease by polymerase chain reaction analysis. Blood. 1994;83(8):2238–47.PubMedGoogle Scholar
  77. 77.
    Bungaro S, Dell’Orto MC, Zangrando A, Basso D, Gorletta T, Lo Nigro L, et al. Integration of genomic and gene expression data of childhood ALL without known aberrations identifies subgroups with specific genetic hallmarks. Genes Chromosomes Cancer. 2009;48(1):22–38.PubMedGoogle Scholar
  78. 78.
    Kawamata N, Ogawa S, Zimmermann M, Kato M, Sanada M, Hemminki K, et al. Molecular allelokaryotyping of pediatric acute lymphoblastic leukemias by high-resolution single nucleotide polymorphism oligonucleotide genomic microarray. Blood. 2008;111(2):776–84.PubMedGoogle Scholar
  79. 79.
    Kawamata N, Ogawa S, Seeger K, Kirschner-Schwabe R, Huynh T, Chen J, et al. Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia. Int J Oncol. 2009; 34(6):1603–12.PubMedGoogle Scholar
  80. 80.
    Paulsson K, Forestier E, Lilljebjorn H, Heldrup J, Behrendtz M, Young BD, et al. Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2010;107(50):21719–24.PubMedGoogle Scholar
  81. 81.
    Gondek LP, Tiu R, O’Keefe CL, Sekeres MA, Theil KS, Maciejewski JP. Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood. 2008;111(3):1534–42.PubMedGoogle Scholar
  82. 82.
    Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007; 446(7137):758–64.PubMedGoogle Scholar
  83. 83.
    Haferlach T, Kohlmann A, Wieczorek L, Basso G, Kronnie GT, Bene MC, et al. Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the international microarray innovations in leukemia study group. J Clin Oncol. 2010;28(15):2529–37.PubMedGoogle Scholar
  84. 84.
    Collins-Underwood JR, Mullighan CG. Genomic profiling of high-risk acute lymphoblastic leukemia. Leukemia. 2010;24(10):1676–85.PubMedGoogle Scholar
  85. 85.
    Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST, et al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol. 2009;10(2):125–34.Google Scholar
  86. 86.
    Gutierrez A, Dahlberg SE, Neuberg DS, Zhang J, Grebliunaite R, Sanda T, et al. Absence of biallelic TCRgamma deletion predicts early treatment failure in pediatric T-cell acute lymphoblastic leukemia. J Clin Oncol. 2010;28(24):3816–23.PubMedGoogle Scholar
  87. 87.
    Kang H, Chen IM, Wilson CS, Bedrick EJ, Harvey RC, Atlas SR, et al. Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Blood. 2010;115(7):1394–405.PubMedGoogle Scholar
  88. 88.
    Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10(2):147–56.PubMedGoogle Scholar
  89. 89.
    Burmeister T, Gökbuget N, Reinhardt R, Rieder H, Hoelzer D, Schwartz S. NUP214-ABL1 in adult T-ALL: the GMALL study group experience. Blood. 2006;1081(10):3556–9.Google Scholar
  90. 90.
    Cauwelier B, Dastugue N, Cools J, Poppe B, Herens C, De PA, et al. Molecular cytogenetic study of 126 unselected T-ALL cases reveals high incidence of TCRbeta rearrangements and putative new T-cell oncogenes. Leukemia. 2006;20:1238–44.PubMedGoogle Scholar
  91. 91.
    Flex E, Petrangeli V, Stella L, Chiaretti S, Hornakova T, Knoops L, et al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J Exp Med. 2008;205(4):751–8.PubMedGoogle Scholar
  92. 92.
    Graux C, Cools J, Melotte C, Quentmeier H, Ferrando A, Levine R, et al. Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet. 2004; 36(10):1084–9.PubMedGoogle Scholar
  93. 93.
    Rao SS, O’Neil J, Liberator CD, Hardwick JS, Dai X, Zhang T, et al. Inhibition of NOTCH signaling by gamma secretase inhibitor engages the RB pathway and elicits cell cycle exit in T-cell acute lymphoblastic leukemia cells. Cancer Res. 2009;69(7):3060–8.PubMedGoogle Scholar
  94. 94.
    Real PJ, Tosello V, Palomero T, Castillo M, Hernando E, de Stanchina E, et al. Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nat Med. 2009;15(1):50–8.PubMedGoogle Scholar
  95. 95.
    Downing JR. Acute leukemia: subtype discovery and prediction of outcome by gene expression profiling. Verh Dtsch Ges Pathol. 2003;87:66–71.PubMedGoogle Scholar
  96. 96.
    Mullighan CG, Su X, Zhang J, Radtke I, Phillips LA, Miller CB, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470–80.PubMedGoogle Scholar
  97. 97.
    Harvey RC, Mullighan CG, Wang X, Dobbin KK, Davidson GS, Bedrick EJ, et al. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome. Blood. 2010;116(23):4874–84.PubMedGoogle Scholar
  98. 98.
    Izraeli S. Application of genomics for risk stratification of childhood acute lymphoblastic leukaemia: from bench to bedside? Br J Haematol. 2010;151(2):119–31.PubMedGoogle Scholar
  99. 99.
    Roll JD, Reuther GW. CRLF2 and JAK2 in B-progenitor acute lymphoblastic leukemia: a novel association in oncogenesis. Cancer Res. 2010;70(19):7347–52.PubMedGoogle Scholar
  100. 100.
    Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LA, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA. 2009;106(23):9414–8.PubMedGoogle Scholar
  101. 101.
    Bercovich D, Ganmore I, Scott LM, Wainreb G, Birger Y, Elimelech A, et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with down’s syndrome. Lancet. 2008;372(9648):1484–92.PubMedGoogle Scholar
  102. 102.
    Mullighan CG. New strategies in acute lymphoblastic leukemia: translating advances in genomics into clinical practice. Clin Cancer Res. 2011;17(3):396–400.PubMedGoogle Scholar
  103. 103.
    Roberts KG, Mullighan CG. How new advances in genetic analysis are influencing the understanding and treatment of childhood acute leukemia. Curr Opin Pediatr. 2011;23(1):34–40.PubMedGoogle Scholar
  104. 104.
    Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999;286(5439):531–7.PubMedGoogle Scholar
  105. 105.
    Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet. 2002;30(1):41–7.PubMedGoogle Scholar
  106. 106.
    Kohlmann A, Kipps TJ, Rassenti LZ, Downing JR, Shurtleff SA, Mills KI, et al. An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the microarray innovations in LEukemia study prephase. Br J Haematol. 2008;142(5):802–7.PubMedGoogle Scholar
  107. 107.
    Song JH, Kim HJ, Lee CH, Kim SJ, Hwang SY, Kim TS. Identification of gene expression signatures for molecular classification in human leukemia cells. Int J Oncol. 2006; 29(1):57–64.PubMedGoogle Scholar
  108. 108.
    Basso G, Case C, Dell’Orto MC. Diagnosis and genetic subtypes of leukemia combining gene expression and flow cytometry. Blood Cells Mol Dis. 2007;39(2):164–8.PubMedGoogle Scholar
  109. 109.
    Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009; 361(11):1058–66.PubMedGoogle Scholar
  110. 110.
    Meeker ND, Yang JJ, Schiffman JD. Pharmacogenomics of pediatric acute lymphoblastic leukemia. Expert Opin Pharmacother. 2010;11(10):1621–32.PubMedGoogle Scholar
  111. 111.
    Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002;1(2):133–43.PubMedGoogle Scholar
  112. 112.
    Holleman A, den Boer ML, de Menezes RX, Cheok MH, Cheng C, Kazemier KM, et al. The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia. Blood. 2006;107(2):769–76.PubMedGoogle Scholar
  113. 113.
    Chiusolo P, Reddiconto G, Farina G, Mannocci A, Fiorini A, Palladino M, et al. MTHFR polymorphisms’ influence on outcome and toxicity in acute lymphoblastic leukemia patients. Leuk Res. 2007;31(12):1669–74.PubMedGoogle Scholar
  114. 114.
    Huang L, Tissing WJ, de Jonge R, van Zelst BD, Pieters R. Polymorphisms in folate-related genes: association with side effects of high-dose methotrexate in childhood acute lymphoblastic leukemia. Leukemia. 2008;22(9):1798–800.PubMedGoogle Scholar
  115. 115.
    Kager L, Cheok M, Yang W, Zaza G, Cheng Q, Panetta JC, et al. Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics. J Clin Invest. 2005;115(1):110–7.PubMedGoogle Scholar
  116. 116.
    Kishi S, Cheng C, French D, Pei D, Das S, Cook EH, et al. Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood. 2007;109(10):4151–7.PubMedGoogle Scholar
  117. 117.
    Marino S, Verzegnassi F, Tamaro P, Stocco G, Bartoli F, Decorti G, et al. Response to glucocorticoids and toxicity in childhood acute lymphoblastic leukemia: role of polymorphisms of genes involved in glucocorticoid response. Pediatr Blood Cancer. 2009;53(6):984–91.PubMedGoogle Scholar
  118. 118.
    Bolufer P, Collado M, Barragan E, Calasanz MJ, Colomer D, Tormo M, et al. Profile of polymorphisms of drug-metabolising enzymes and the risk of therapy-related leukaemia. Br J Haematol. 2007;136(4):590–6.PubMedGoogle Scholar
  119. 119.
    Fleury I, Primeau M, Doreau A, Costea I, Moghrabi A, Sinnett D, et al. Polymorphisms in genes involved in the corticosteroid response and the outcome of childhood acute lymphoblastic leukemia. Am J Pharmacogenomics. 2004;4(5):331–41.PubMedGoogle Scholar
  120. 120.
    Lennard L, Lilleyman JS, Van Loon J, Weinshilboum RM. Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet. 1990;336(8709): 225–9.PubMedGoogle Scholar
  121. 121.
    McLeod HL, Krynetski EY, Relling MV, Evans WE. Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia. 2000;14(4):567–72.PubMedGoogle Scholar
  122. 122.
    Schmiegelow K, Forestier E, Kristinsson J, Soderhall S, Vettenranta K, Weinshilboum R, et al., Nordic Society of Paediatric Haematology and Oncology. Thiopurine methyltransferase activity is related to the risk of relapse of childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study. Leukemia. 2009;23(3):557–64.Google Scholar
  123. 123.
    Stanulla M, Schaeffeler E, Flohr T, Cario G, Schrauder A, Zimmermann M, et al. Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA. 2005;293(12):1485–9.PubMedGoogle Scholar
  124. 124.
    Relling MV, Pui CH, Cheng C, Evans WE. Thiopurine methyltransferase in acute lymphoblastic leukemia. Blood. 2006;107(2):843–4.PubMedGoogle Scholar
  125. 125.
    Relling MV, Hancock ML, Boyett JM, Pui CH, Evans WE. Prognostic importance of 6-mercaptopurine dose intensity in acute lymphoblastic leukemia. Blood. 1999;93(9):2817–23.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department PathologyUniversity of Arkansas for Medical SciencesLittle RockUSA
  2. 2.Department of Pathology and Laboratory MedicinUniversity of North Carolina at Chapel HillChapel HillUSA

Personalised recommendations