Seminars in Hematology
Volume 40, Issue 4 , Pages 268-273 , October 2003

MLL-rearranged leukemias: insights from gene expression profiling

  • Scott A Armstrong

      Affiliations

    • Departments of Pediatric Oncology, Cancer, Immunology and AIDS, and Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    • The Whitehead Institute Genome Center, Cambridge, MA, USA
  • ,
  • Todd R Golub

      Affiliations

    • Departments of Pediatric Oncology, Cancer, Immunology and AIDS, and Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
  • ,
  • Stanley J Korsmeyer

      Affiliations

    • Departments of Pediatric Oncology, Cancer, Immunology and AIDS, and Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    • Corresponding Author InformationAddress correspondence to Stanley J. Korsmeyer, MD, Dana-Farber Cancer Institute, One Jimmy Find Way, Boston, MA 02115, USA

References 

  1. Allander SV, Nupponen NN, Ringner M, et al.  Gastrointestinal stromal tumors with KIT mutations exhibit a remarkably homogeneous gene expression profile. Cancer Res. 2001;61:8624–8628
  2. Armstrong SA, Hsieh JJ, Korsmeyer SJ. Genomic approaches to the pathogenesis and treatment of acute lymphoblastic leukemias. Curr Opin Hematol. 2002;9:339–344
  3. Armstrong SA, Kung AL, Mabon ME, et al.  Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell. 2003;3:173–183
  4. Armstrong SA, Staunton JE, Silverman LB, et al.  MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet. 2002;30:41–47
  5. Ayton PM, Cleary ML. Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene. 2001;20:5695–5707
  6. Biondi A, Cimino G, Pieters R, et al.  Biological and therapeutic aspects of infant leukemia. Blood. 2000;96:24–33
  7. Borrow J, Shearman AM, Stanton VP, et al.  The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet. 1996;12:159–167
  8. Buske C, Humphries RK. Homeobox genes in leukemogenesis. Int J Hematol. 2000;71:301–308
  9. Chen CS, Sorensen PH, Domer PH, et al.  Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood. 1993;81:2386–2393
  10. Cumano A, Paige CJ, Iscove NN, et al.  Bipotential precursors of B cells and macrophages in murine fetal liver. Nature. 1992;356:612–615
  11. Dannaeus K, Johannisson A, Nilsson K, et al.  Flt3 ligand induces the outgrowth of Mac-1+B220+ mouse bone marrow progenitor cells restricted to macrophage differentiation that coexpress early B cell-associated genes. Exp Hematol. 1999;27:1646–1654
  12. Debernardi S, Lillington DM, Chaplin T, et al.  Genome-wide analysis of acute myeloid leukemia with normal karyotype reveals a unique pattern of homeobox gene expression distinct from those with translocation-mediated fusion events. Genes Chromosomes Cancer. 2003;37:149–158
  13. Demetri GD, von Mehren M, Blanke CD, et al.  Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–480
  14. DiMartino JF, Miller T, Ayton PM, et al.  A carboxy-terminal domain of ELL is required and sufficient for immortalization of myeloid progenitors by MLL-ELL. Blood. 2000;96:3887–3893
  15. Domer PH, Fakharzadeh SS, Chen CS, et al.  Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product. Proc Natl Acad Sci USA. 1993;90:7884–7888
  16. Druker BJ, Talpaz M, Resta DJ, et al.  Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031–1037
  17. Felix CA, Hosler MR, Winick NJ, et al.  ALL-1 gene rearrangements in DNA topoisomerase II inhibitor-related leukemia in children. Blood. 1995;85:3250–3256
  18. Ferrando AA, Armstrong SA, Neuberg DS, et al.  Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias (Dominance of HOX dysregulation). Blood. 2003;102:262–268
  19. Ferrando AA, Neuberg DS, Staunton J, et al.  Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell. 2002;1:75–87
  20. Gorre ME, Mohammed M, Ellwood K, et al.  Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293:876–880
  21. Greaves MF, Chan LC, Furley AJ, et al.  Lineage promiscuity in hemopoietic differentiation and leukemia. Blood. 1986;67:1–11
  22. Gu Y, Nakamura T, Alder H, et al.  The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. Cell. 1992;71:701–708
  23. Hess JL, Yu BD, Li B, et al.  Defects in yolk sac hematopoiesis in Mll-null embryos. Blood. 1997;90:1799–1806
  24. McCulloch EA. Stem cells in normal and leukemic hemopoiesis (Henry Stratton Lecture, 1982). Blood. 1983;62:1–13
  25. Miettinen M, Majidi M, Lasota J. Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs) (A review). Eur J Cancer. 2002;38(suppl 5):S39–S51
  26. Milne TA, Briggs SD, Brock HW, et al.  MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol Cell. 2002;10:1107–1117
  27. Montecino-Rodriguez E, Leathers H, Dorshkind K. Bipotential B-macrophage progenitors are present in adult bone marrow. Nat Immunol. 2001;2:83–88
  28. Nakamura T, Largaespada DA, Lee MP, et al.  Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nat Genet. 1996;12:154–158
  29. Nakamura T, Mori T, Tada S, et al.  ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell. 2002;10:1119–1128
  30. Owens BM, Hawley RG. HOX and non-HOX homeobox genes in leukemic hematopoiesis. Stem Cells. 2002;20:364–379
  31. Rowley JD. The critical role of chromosome translocations in human leukemias. Annu Rev Genet. 1998;32:495–519
  32. Rubnitz JE, Raimondi SC, Tong X, et al.  Favorable impact of the t(9;11) in childhood acute myeloid leukemia. J Clin Oncol. 2002;20:2302–2309
  33. Silverman LB, McLean TW, Gelber RD, et al.  Intensified therapy for infants with acute lymphoblastic leukemia (Results from the Dana-Farber Cancer Institute Consortium). Cancer. 1997;80:2285–2295
  34. So CW, Karsunky H, Passegue E, et al.  MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell. 2003;3:161–171
  35. Thorsteinsdottir U, Mamo A, Kroon E, et al.  Overexpression of the myeloid leukemia-associated Hoxa9 gene in bone marrow cells induces stem cell expansion. Blood. 2002;99:121–129
  36. Thorsteinsdottir U, Sauvageau G, Humphries RK. Enhanced in vivo regenerative potential of HOXB4-transduced hematopoietic stem cells with regulation of their pool size. Blood. 1999;94:2605–2612
  37. Tkachuk DC, Kohler S, Cleary ML. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell. 1992;71:691–700
  38. Yamamoto Y, Kiyoi H, Nakano Y, et al.  Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood. 2001;97:2434–2439
  39. Yeoh EJ, Ross ME, Shurtleff SA, et al.  Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002;1:133–143
  40. Yu BD, Hanson RD, Hess JL, et al.  MLL, a mammalian trithorax-group gene, functions as a transcriptional maintenance factor in morphogenesis. Proc Natl Acad Sci USA. 1998;95:10632–10636
  41. Yu BD, Hess JL, Horning SE, et al.  Altered Hox expression and segmental identity in Mll-mutant mice. Nature. 1995;378:505–508
  42. Zeisig BB, Garcia-Cuellar MP, Winkler TH, et al.  The oncoprotein MLL-ENL disturbs hematopoietic lineage determination and transforms a biphenotypic lymphoid/myeloid cell. Oncogene. 2003;22:1629–1637
  43. Ziemin-van der Poel S, McCabe NR, Gill HJ, et al.  Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci USA. 1991;88:10735–10739

PII: S0037-1963(03)00196-3

doi: 10.1016/S0037-1963(03)00196-3

Seminars in Hematology
Volume 40, Issue 4 , Pages 268-273 , October 2003