MLL fusion genes in the 11q23 acute leukemias

  • James R. Downing
  • A. Thomas Look
Part of the Cancer Treatment and Research book series (CTAR, volume 84)


Remarkable progress has been made over the last five years in defining the molecular pathogenesis of the acute leukemias. Of the many leukemia-specific cytogenetic abnormalities that have been identified to date, structural lesions within the 11q23 chromosomal band are among the most common [1–4]. Translocations, deletions, and inversions within 11q23 have been detected in a variety of hematopoietic malignancies, including 7%–10% of the acute lymphoblastic leukemias (ALLs), 5%–6% of the acute myeloblasts leukemias (AMLs), and as many as 85% of secondary leukemias occurring in patients treated with topoisomerase II inhibitors [2,3,5–8]. Incidence rates of 11q23 translocations are strikingly high in infants (80% of ALL cases and 45% of AML), making these rearrangements the most common cytogenetic abnormalities in acute leukemias of this age group [9–11]. A number of different reciprocal chromosome bands have been shown to participate in balanced 11q23 translocations, including 1p32, 1q21, 2p21, 4q21, 5q31, 6q27, 7p15, 9p22, 10q12, 15q15, 16p13, 17q21, 19pl3, and Xql3, with the most common translocations being t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23; p13) [1]. Although some of these rearrangements are found almost exclusively in ALL (e.g., t(4;11)) or AML (e.g., t(9;11)), the majority have been observed in both myeloid and lymphoid leukemias, suggesting transformation of a pluripotent progenitor cell [1,12–16].


Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Acute Leukemia Breakpoint Cluster Region 11q23 Translocation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mitelman F (1994). Catalog of Chromosome Aberrations in Cancer, 5th ed.Google Scholar
  2. 2.
    Raimondi SC, Kalwinsky DK, Hayashi Y, Behm FG, Mirro J Jr, Williams DL (1989). Cytogenetics of childhood acute nonlymphocytic leukemia. Cancer Genet Cytogenet 40:13–27.PubMedCrossRefGoogle Scholar
  3. 3.
    Raimondi SC, Peiper SC, Kitchingman GR, Behm FG, Williams DL, Hancock ML, Mirro J (1989). Childhood acute lymphoblastic leukemia with chromosomal breakpoints at 11q23. Blood 73:1627–1634.PubMedGoogle Scholar
  4. 4.
    Raimondi SC (1993). Current status of cytogenetic research in childhood acute lymphoblastic leukemia. Blood 70:2237–2251.Google Scholar
  5. 5.
    DeVore R, Whitlock J, Hainsworth JD, Johnson DH (1989). Therapy-related acute nonlymphocytic leukemia with monocytic features and rearrangement of chromosome 11q. Ann Intern Med 110:740–742.Google Scholar
  6. 6.
    Pui C-H, Behm FG, Raimondi SC, Dodge RK, George SL, Rivera GK, Mirro J, Kalwinsky DK, Dahl GV, Murphy SB, Crist WM, Williams DL (1989). Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia. N Engl J Med 321:136–142.PubMedCrossRefGoogle Scholar
  7. 7.
    Pedersen-Bjergaard J, Daugaard G, Werner Hansen S, Philip P, Larsen SO, Rorth M (1991). Increased risk of myelodysplasia and leukemia following etoposide and cisplatin for germ cell tumors. Proc Am Soc Clin Oncol 10:221a.Google Scholar
  8. 8.
    Pui C-H, Ribeiro RC, Hancock ML, Rivera GK, Evans WE, Raimondi SC, Head DR, Behm FG, Mahmoud MH, Sandlund JT, Crist WM (1991). Acute myeloid leukemia in children treated with epipodophyllotoxins for acute lymphoblastic leukemia. N Engl J Med 325:1682–1687.PubMedCrossRefGoogle Scholar
  9. 9.
    Pui C-H, Frankel LS, Carroll AJ, Raimondi SC, Shuster JJ, Head DR, Crist WM, Land VJ, Pullen DJ, Steuber CP, Behm FG, Borowitz MJ (1991). Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases. Blood 77:440–447.PubMedGoogle Scholar
  10. 10.
    Kaneko Y, Maseki N, Takasaki M, Sakurai T, Hayashi Y, Nakazawa S, Mori T, Sakurai M, Takeda T, Shikano T, Hiroshi Y (1986). Clinical and hematologic characteristics in acute leukemia with 11q23 translocations. Blood 67:484–488.PubMedGoogle Scholar
  11. 11.
    Heerema NA, Arthur DC, Sather H, Albo V, Feusner J, Lange BJ, Steinherz PG, Zeltzer P, Hammond D, Reaman GH (1994). Cytogenetic features of infants less than 12 months of age at diagnosis of acute lymphoblastic leukemia: impact of the 11q23 breakpoint on outcome: a report of the Children’s Cancer Group. Blood 83:2274–2284.PubMedGoogle Scholar
  12. 12.
    Arthur DC, Bloomfield CD, Linquist LL, Nesbit MEJ (1982). Translocation 4;11 in acute lymphoblastic leukemia: clinical characteristics and prognostic significance. Blood 59:96–99.PubMedGoogle Scholar
  13. 13.
    Kaneko Y, Rowley JD, Maurer HS, Variakojis D, Moohr JW (1982). Chromosome pattern in childhood acute nonlymphocytic leukemia (ANLL). Blood 60:389–399.PubMedGoogle Scholar
  14. 14.
    Nagasaka M, Maeda S, Maeda H, Chen HL, Kita K, Mabuchi O, Misu H, Matsuo T, Sugiyama T (1983). Four cases of t(4;11) acute leukemia and its myelomonocytic nature in infants. Blood 61:1174–1181.PubMedGoogle Scholar
  15. 15.
    Stong RC, Korsmeyer SJ, Parkin JL, Arthur DC, Kersey JH (1985). Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B-lineage and monocytic characteristics. Blood 65:21–31.PubMedGoogle Scholar
  16. 16.
    Mirro J, Kitchingman G, Williams D, Lauzon GJ, Lin C, Callihan T, Zipf TF (1986). Clinical and laboratory characteristics of acute leukemia with the 4;11 translocation. Blood 67:689–697.PubMedGoogle Scholar
  17. 17.
    Parkin JL, Arthur DC, Abramson CS, McKenna RW, Kersey JH, Heideman RL, Brunning RD (1982). Acute leukemia associated with the t(4;11) chromosome rearrangement: ultra-structural and immunologic characteristics. Blood 60:1321–1331.PubMedGoogle Scholar
  18. 18.
    Crist WM, Cleary ML, Grossi CE, Prasthofer EF, Heggie GD, Omurra G A, Carroll AJ, Link MP, Sklar J (1985). Acute leukemias associated with the 4;11 chromosome translocation have rearranged immunoglobulin heavy chain genes. Blood 66:33–38.PubMedGoogle Scholar
  19. 19.
    Bloomfield CD, Seeker-Walker LM, Goldman A, Van den Berghe H, de la Chappelle A, Ruutu T, Alimena G, Garson OM, Golomb HM, Rowley JD, Kaneko Y, Whang-Peng J, Prigogina E, Phillip P, Sandberg AA, Lawler SD, Mitelman F (1989). Six-year follow-up of the clinical significance of karyotype in acute lymphoblastic leukemia. Cancer Genet Cytogenet 40:171–185.PubMedCrossRefGoogle Scholar
  20. 20.
    Bloomfield CD, Goldman AI, Alimena G, Berger R, Borgstrom GH, Brandt L, Catovsky D, de la Chapelle A, Dewald GW, Garson OM, Garwicz S, Golomb HM, Hossfeld DK, Lawler SD, Mitelman F, Nilsson P, Pierre RV, Philip P, Prigogina E, Rowley JD, Sakurai M, Sandberg AA, Secker-Walker LM, Tricot G, Van Den Berghe H, Van Orshoven A, Vuopio P, Whang-Peng J (1986). Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia. Blood 67:415–420.PubMedGoogle Scholar
  21. 21.
    Stock W, Thirman MJ, Dodge RK, Rowley JD, Diaz MO, Wurster-Hill D, Sobol RE, Davey FR, Larson RA, Westbrook CA, Bloomfield CD (1994). Detection of MLL gene rearrangements in adult acute lymphoblastic leukemia. A cancer and leukemia group B study. Leukemia 8:1918–1922.PubMedGoogle Scholar
  22. 22.
    Diaz MO, Le Beau MM, Pitha P, Rowley JD (1986) Interferon and c-ets-1 genes in the translocation (9;11)(p22;q23) in human acute monocytic leukemia. Science 231:265–267.PubMedCrossRefGoogle Scholar
  23. 23.
    Bower M, Parry P, Carter M, Lillington DM, Amess J, Lister TA, Evans G, Young BD (1994). Prevalence and clinical correlations of MLL gene rearrangements in AML-M4/5. Blood 84:3776–3780.PubMedGoogle Scholar
  24. 24.
    Sorensen HB, Chen C, Smith FO, Arthur DC, Domer PH, Bernstein ID, Korsmeyer SJ, Hammond GD, Kersey JH (1994). Molecular rearrangements of the MLL gene are present in most cases of infant acute myeloid leukemia and are strongly correlated with monocytic or myelomonocytic phenotypes. J Clin Invest 93:429–437.PubMedCrossRefGoogle Scholar
  25. 25.
    Rowley JD, Diaz MO, Espinosa R, Patel YD, van Melle E, Ziemin S, Taillon-Miller P, Lichter P, Evans GA, Kersey JH (1990). Mapping chromosome band 11q23 in human acute leukemia with biotinylated probes: identification of 11q23 translocation breakpoints with a yeast artificial chromosome. Proc Natl Acad Sci USA 87:9358–9362.PubMedCrossRefGoogle Scholar
  26. 26.
    Ziemin-van der Poel S, McCabe NR, Gill HJ, Espinosa R, Patel Y, Harden A, Rubinelli P, Smith SD, Lebeau MM, Rowley JD, Diaz MO (1991). Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci USA 88:10735–10739.CrossRefGoogle Scholar
  27. 27.
    Cimino G, Moir DT, Canaani O, Williams K, Crist WM, Katzav S, Cannizzaro L, Lange B, Nowell PC, Croce CM, Canaani E (1991). Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations. Cancer Res 51:6712–6714.PubMedGoogle Scholar
  28. 28.
    Tkachuk DC, Kohler S, Cleary ML (1992). Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell 71:691–700.PubMedCrossRefGoogle Scholar
  29. 29.
    Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G, Croce CM, Cananni E (1992). The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithoriax, to the AF-4 gene. Cell 71:701–708.PubMedCrossRefGoogle Scholar
  30. 30.
    Parry P, Djabali M, Bower M, Khristich J, Waterman M Gibbons B, Young BD, Evans G (1993). Structure and expression of the human trithorax-like gene 1 involved in acute leukemias. Proc Natl Acad Sci USA 90:4738–4742.PubMedCrossRefGoogle Scholar
  31. 31.
    McCabe NR, Burnett RC, Gill HJ, Thirman MJ, Mbangkollo D, Kipiniak M, vanMelle E, Ziemin-van der Poel S, Rowley JD, Diaz MO (1992). Cloning of cDNAs of the MLL gene that detect DNA rearrangements and altered RNA transcripts in human leukemic cells with 11q23 translocations. Proc Natl Acad Sci USA 89:11794–11798.PubMedCrossRefGoogle Scholar
  32. 32.
    Ma Q, Alder H, Nelson KK, Chatterjee D, Gu Y, Nakamura T, Canaani E, Croce CM, Siracusa LD, Buchberg AM (1993). Analysis of the murine ALL-1 gene reveals conserved domains with human ALL-1 and identified a motif shared with DNA methyltransferases. Proc Natl Acad Sci USA 90:6350–6354.PubMedCrossRefGoogle Scholar
  33. 33.
    Domer PH, Fakharzadeh SS, Chen CS, Jockei J, Johansen L, Silverman GA, Kersey JH, Korsmeyer SJ (1993). Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product. Proc Natl Acad Sci USA 90:7884–7888.PubMedCrossRefGoogle Scholar
  34. 34.
    Ingham PW (1985). Genetic control of the spatial pattern of selector gene expression in Drosophila. Cold Spring Harbor Symp Quant Biol 50:201–208.PubMedGoogle Scholar
  35. 35.
    Mazo AM, Huang DH, Mozer BA, Dawid IB (1990). The trithorax gene, a trans-acting regulator of the bithorax-complex in Drosophila, encodes a protein with zinc-binding domains. Proc Natl Acad Sci USA 87:2112–2116.PubMedCrossRefGoogle Scholar
  36. 36.
    Jones RS, Gelbart WM (1993). The Drosophila polycomb-group gene enhancer of zeste contains a region with sequence similarity to trithorax. Mol Cell Biol 13:6357–6366.PubMedGoogle Scholar
  37. 37.
    Zeleznik-Le NJ, Harden AM, Rowley JD (1994). 11q23 translocations split the ‘AT-hook’ cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc Natl Acad Sci USA 91:10610–10614.PubMedCrossRefGoogle Scholar
  38. 38.
    Thirman MJ, Gill HJ, Burnett RC, Mbangkollo D, McCabe NR, Kobayashi H, Ziemin-van der Poel S, Kaneko Y, Morgan R, Sandberg AA, Chaganti RSK, Larson RA, Le Beau MM, Diaz MO, Rowley JD (1993). Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med 329:909–914.PubMedCrossRefGoogle Scholar
  39. 39.
    Chen C, Sorensen PHB, Domer PH, Reaman GH, Korsmeyer SJ, Heerema NA, Hammond GD, Kersey JH (1993). Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood 81:2386–2393.PubMedGoogle Scholar
  40. 40.
    Gu Y, Alder H, Nakamura T, Schichman SA, Prasad R, Canaani O, Saito H, Croce CM, Canaani E (1994). Sequence analysis of the breakpoint cluster region in the ALL-1 gene involved in acute leukemia. Cancer Res 54:2327–2330.PubMedGoogle Scholar
  41. 41.
    Rowley JD (1992). The der(11) chromosome contains the critical breakpoint junction in the 4;11, 9;11, and 11;19 translocations in acute leukemia. Genes Chrom Cancer 5:264–266.PubMedCrossRefGoogle Scholar
  42. 42.
    Downing JR, Head DR, Raimondi SC, Carroll AJ, Curcio-Brint AM, Motroni TA, Hulshof MG, Pullen J, Domer PH (1994). The der(11)-encoded MLL/AF-4 fusion transcript is consistently detected in t(4;11)(q21;q23)-containing acute lymphoblastic leukemia. Blood 83:330–335.PubMedGoogle Scholar
  43. 43.
    Borkhardt A, Repp R, Haupt E, Brettreich S, Buchen U, Gossen R, Lampert P (1994). Moleular analysis of MLL-1/AF4 recombination in infant acute lymphoblastic leukemia. Leukemia 8:549–553.PubMedGoogle Scholar
  44. 44.
    Morrissey J, Tkachuk DC, Milatovich A, Francke U, Link M, Cleary ML (1993). A serine/proline-rick protein is fused to HRX in t(4;11) acute leukemias. Blood 81:1124–1131.PubMedGoogle Scholar
  45. 45.
    Rubnitz JE, Morrissey J, Savage PA, Cleary ML (1994). ENL, the gene fused withHRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells. Blood 84:1747–1752.PubMedGoogle Scholar
  46. 46.
    Nakamura T, Alder H, Gu Y, Prasad R, Canaani O, Kamada N, Gale RP, Lange B, Crist WM, Nowell PC, Croce CM, Canaani E (1993). Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequnce homology and/or common motifs. Proc Natl Acad Sci USA 90:4631–4635.PubMedCrossRefGoogle Scholar
  47. 47.
    Iida S, Seot M, Yamamoto K, Komatsu H, Tojo A, Asano S, Kamada N, Ariyoshi Y, Takahashi T, Ueda R (1993). MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 in 19pl3. Oncogene 8:3085–3092.PubMedGoogle Scholar
  48. 48.
    Corral J, Forster A, Thompson S, Lampert F, Kaneko Y, Slater R, Kroes WG, Van der Schoot CE, Ludwig WD, Karpas A, Pocock C, Cotter F, Rabbitts TH (1993). Acute leukemias of different lineages have similar MLL gene fusions encoding related chimeric proteins resulting from chromosomal translocation. Proc Natl Acad Sci USA 90:8538–8542.PubMedCrossRefGoogle Scholar
  49. 49.
    Parry P, Wei Y, Evans G (1994). Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family. Genes Chrom Cancer 11:79–84.PubMedCrossRefGoogle Scholar
  50. 50.
    Thirman MJ, Levitan DA, Kobayashi H, Simon MC, Rowley JD (1994). Cloning of ELL, a gene that fuses of MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia. Proc Natl Acad Sci USA 91;12110–12114.PubMedCrossRefGoogle Scholar
  51. 51.
    Chaplin T, Ayton P, Bernard O A, Saha V, Delia Valle V, Hillion J, Gregorini A, Lillington D, Berger R, Young BD (1995). A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia. Blood 85:11435–11441.Google Scholar
  52. 52.
    Prasad R, Leshkowitz D, Gu Y, Alder H, Nakamura T, Saito H, Huebner K, Berger R, Croce CM, Canaani E (1994). Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1 (MLL) in acute leukemia. Proc Natal Acad Sci USA 91:8107–8111.CrossRefGoogle Scholar
  53. 53.
    Tse W, Zhu W, Chen HS, Cohen A (1995). A novel gene, AF1q, fused to MLL in t(1;11)(q21;q23), is specifically expressed in leukemic and immature hematopoietic cells. Blood 85:650–656.PubMedGoogle Scholar
  54. 54.
    McCabe NR, Kipiniak M, Kobayashi H, Thirman M, Gill H, Rowley JD, Diaz MO (1994). DNA rearrangements and altered transcripts of the MLL gene in a human T-ALL cell line karpas 45 with a t(X;11)(ql3;q23) translocation. Genes Chrom Cancer 9:221–224.PubMedCrossRefGoogle Scholar
  55. 55.
    Prasad R, Gu Y, Alder H, Nakamura T, Canaani O, Saito H, Huebner K, Gale RP, Nowell PC, Kuriyama K, Miyazaki Y, Croce CM, Canaani E (1993). Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation. Cancer Res 53:5624–5628.PubMedGoogle Scholar
  56. 56.
    Cleary ML (1993). A promiscuous oncogene in acute leukemia. N Engl J Med 329:958–959.PubMedCrossRefGoogle Scholar
  57. 57.
    Caligiuri MA, Schichman SA, Strout MP, Mrozek K, Baer MR, Frankel SR, Barcos M, Herzig GP, Croce CM, Bloomfield CD (1994). Molecular rearrangment of the ALL-1 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocations. Cancer Res 54:370–373.PubMedGoogle Scholar
  58. 58.
    Schichman SA, Caligiuri MA, Gu Y, Strout MP, Canaani E, Bloomfield CD, Croce CM (1994). ALL-1 partial duplication in acute leukemia. Proc Natl Acad Sci 91:6236–6239.PubMedCrossRefGoogle Scholar
  59. 59.
    Schichman SA, Caligiuri MA, Strout MP, Carter SL, Gu Y, Canaani E, Bloomfield CD, Crocel CM (1994). ALL-1 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements. Cancer Res 54:4277–4280.PubMedGoogle Scholar
  60. 60.
    Hudson MM, Raimondi SC, Behm FG, Pui C (1991). Childhood acute leukemia with t(11;19)(q23;pl3). Leukemia 5:1064–1068.PubMedGoogle Scholar
  61. 61.
    Greaves MF, Chan LC, Furley AJ, Watt SM, Molgaard HV (1986). Lineage promiscuity in hemopoietic differentiation and leukemia. Blood 67:1–11.PubMedGoogle Scholar
  62. 62.
    Ford AM, Ridge SA, Cabrera ME, Mahmoud H, Steel CM, Chan LC, Greaves M (1993). In utero rearrangements in the trithorax-related oncogene in infant leukaemias. Nature 363:358–360.PubMedCrossRefGoogle Scholar
  63. 63.
    Super HJG, Rothberg PG, Kobayashi H, Freeman AI, Diaz MO, Rowley JD (1994). Clonal, nonconstitutional rearrangements of the MLL gene in infant twins with acute lymphoblastic leukemia: in utero chromosome rearrangement of 11q23. Blood 83:641–644.Google Scholar
  64. 64.
    Gu Y, Cimino G, Alder H, Nakamura T, Prasad R, Canaani O, Moir DT, Jones C, Nowell PC, Croce CME (1992). The t(4;11)(q21;q23) chromosome translocations in acute leukemias involve the VDJ recombinase. Proc Natl Acad Sci USA 89:10464–10468.PubMedCrossRefGoogle Scholar
  65. 65.
    Negrini M, Felix CA, Martin C, Lange BJ, Nakamura T, Canaani E, Croce CM (1993). Potential topoisomerase II DNA-binding sites at the breakpoints of a t(9;11) chromosome translocation in acute myeloid leukemia. Cancer Res 53:4489–4492.PubMedGoogle Scholar
  66. 66.
    Super HJG, McCabe NR, Thirman MJ, Larson RA, Lebeau MM, Pedersen-Bjergaard J, Philip P, Diaz MO, Rowley JD (1993). Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA-topoisomerase II. Blood 81:3705–3711.Google Scholar
  67. 67.
    Hunger SP, Tkachuk DC, Amylon MD, Link MP, Carroll AJ, Welborn JL, Willman CL, Cleary ML (1993).HRX involvement in de novo and secondary leukemias with diverse chromosome 11q23 abnormalities. Blood 81:3197–3203.PubMedGoogle Scholar
  68. 68.
    Wang JC (1985). DNA topoisomerases. Annu Rev Biochem 54:665–697.PubMedCrossRefGoogle Scholar
  69. 69.
    Bae YS, Kawasaki I, Ikeda H, Liu LF (1988). Illegitimate recombination mediated by calf thymus DNA topoisomerase II in vitro. Proc Natl Acad Sci USA 85:2076–2080.PubMedCrossRefGoogle Scholar
  70. 70.
    Sperry AO, Blasquez VC, Garrard WT (1989). Dysfunction of chromosomal loop attachment sites: illegitimate recombination linked to matrix association regions and topoisomerase II. Proc Natl Acad Sci USA 86:5497–5501.PubMedCrossRefGoogle Scholar
  71. 71.
    Chen C, Medberry PS, Arthur DC, Kersey JH (1991). Breakpoint clustering in t(4;11)(q21;q23) acute leukemia. Blood 78:2498–2504.PubMedGoogle Scholar
  72. 72.
    Lo Coco F, Mandelli F, Breccia M, Annino L, Guglielmi C, Petti MC, Testi AM, Alimena G, Croce CM, Canaani E, Cimino G (1993). Southern blot analysis of ALL-1 rearrangements at chromosome 11q23 in acute leukemia. Cancer Res 53:3800–3803.PubMedGoogle Scholar
  73. 73.
    Hilden JM, Chen C, Moore R, Frestedt J, Kersey JH (1993). Herogeneity in ALL/AF-4 fusion messenger RNA detected by polymerase chain reaction in t(4;11) acute leukemia. Cancer Res 53:3853–3856.PubMedGoogle Scholar
  74. 74.
    Biondi A, Rambaldi A, Rossi V, Elia L, Caslini C, Basso Q, Battista R, Barbui T, Mandelli F, Masera G, Croce CM, Canaani E, Cimini G (1993). Detection of ALL-1/AF4 fusion transcript by reverse transcription-polymerase chain reaction for diagnosis and monitoring of acute leukemias with the t(4;11) translocation. Blood 82:2943–2947.PubMedGoogle Scholar
  75. 75.
    Chen C, Hilden JM, Frestedt J, Domer PH, Moore R, Korsmeyer SJ, Kersey JH (1993). The chromosome 4q21 gene (AF-4/FEL) is widely expressed in normal tissues and shows breakpoint diversity in t(4;11)(q21;q23) acute leukemia. Blood 82:1080–1085.PubMedGoogle Scholar
  76. 76.
    Repp R, Borkhardt A, Haupt E, Kreuder J, Brettreich S, Hammermann J, Nishida K, Harbott J, Lampert F (1995). Detection of four different 11q23 chromosomal abnormalities by multi-plex-PCR and fluorescence-based automatic DNA-fragment analysis. Leukemia 9:210–215.PubMedGoogle Scholar
  77. 77.
    Rubnitz JE, Link MP, Shuster JJ, Carroll AJ, Hakami N, Frankel LS, Pullen DJ, Cleary ML (1994). Frequency and prognostic significance of HRX rearrangements in infant acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood 84:570–573.PubMedGoogle Scholar
  78. 78.
    Pui C-H, Behm FG, Downing JR, Hancock ML, Shurtleff SA, Ribeiro RC, Head DR, Mahmoud HH, Sandlund JT, Furman WL, Roberts WM, Crist WM, Raimondi SC (1994). 11q23/MLL rearrangment confers a poor prognosis in infants with acute lymphoblastic leukemia. J Clin Oncol 12:909–915.PubMedGoogle Scholar
  79. 79.
    Raimondi SC, Pui C-H, Downing JR, Head DR, Behm FG (1995). Acute lymphoblastic leukemias with deletion of 11q23 or a novel inversion (11)(pl3q23) lack MLL gene rearrangements and have favorable clinical features. Blood 86:1881–1884.PubMedGoogle Scholar
  80. 80.
    Akato Y, Seto M, Yamamoto K, Iida S, Nakazawa S, Inazawa J, Abe T, Takahashi T, Ueda R (1992). The RCK gene associated with t(11;14) translocation is distinct from the MLL/ALL-1 gene with t(4;11) and t(11;19) translocations. Cancer Res 52:6083–6087.Google Scholar
  81. 81.
    Chen Z, Guidez F, Rousselot P, Agadir A, Chen S, Wang Z, Degos L, Zelent A, Waxman S, Chomienne C (1994). PLZF-RARα fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors. Proc Natl Acad Sci USA 91:1178–1182.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers, Boston 1996

Authors and Affiliations

  • James R. Downing
  • A. Thomas Look

There are no affiliations available

Personalised recommendations