Advertisement

Akute myeloische Leukämien

  • Christa Fonatsch
  • Ilse Schwarzinger
  • Gerlinde Mitterbauer
  • Ulrich Jäger
  • Rotraud Wieser
  • Christine Mannhalter
  • Klaus Lechner
Chapter
Part of the Molekulare Medizin book series (MOLMED)

Zusammenfassung

Die akute myeloische Leukämie (AML) ist eine Gruppe von malignen Erkrankungen, die durch das unkontrollierte Wachstum unreifer hämatologischer Vorläuferzellen (Blasten) bei gleichzeitiger Störung ihrer Differenzierungsfähigkeit gekennzeichnet sind. Die akuten myeloischen Leukämien entstehen in hämatopoetischen Stamm- oder Vorläuferzellen durch genetische Veränderungen, die im Lauf des Lebens erworben werden. Einige wenige Erkrankungen konnten auf äußere mutagene Einflüsse wie Benzol, ionisierende Strahlung oder Chemotherapeutika zurückgeführt werden (Rinsky et al. 1987; Jablon u. Kato 1970). Bei der Mehrheit der Patienten lässt sich jedoch keine spezifische kausale Exposition nachweisen. Eine Ausnahme stellt die Entwicklung einer AML nach Behandlung mit Epipodophyllotoxinen dar.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. Ambros PF, Mehes G, Hattinger C et al. (2001) Unequivocal identification of disseminated tumor cells in the bone marrow by combining immunological and genetic approaches — functional and prognostic information. Leukemia 15:275–277PubMedGoogle Scholar
  2. Baer MR, Stewart CC, Lawrence D et al. (1997) Expression of the neural cell adhesion molecule CD56 is associated with short remission duration and survival in acute myeloid leukemia with t(8;21)(q22;q22). Blood 90:1643–1648PubMedGoogle Scholar
  3. Bain JB (1988) Leukemia diagnosis. Guide to the FAB classification. Wolfe, LondonGoogle Scholar
  4. Beltinger CP, Debatin KM (1998) A simple combined microdissection and aspiration device for the rapid procurement of single cells from clinical peripheral blood smears. Mol Pathol 51:233–236PubMedGoogle Scholar
  5. Bene MC, Castoldi G, Knapp W et al. (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9:1783–1786PubMedGoogle Scholar
  6. Bene MC, Bernier M, Casasnovas RO et al. (1998) The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). Blood 92:596–599PubMedGoogle Scholar
  7. Bennett JM, Catovsky D, Daniel MT et al. (1976) Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 33:451–458PubMedGoogle Scholar
  8. Bennett JM, Catovsky D, Daniel MT et al. (1985 a) Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group. Ann Intern Med 103:460–462PubMedGoogle Scholar
  9. Bennett JM, Catovsky D, Daniel MT et al. (1985 b) Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med 103:620–625PubMedGoogle Scholar
  10. Bennett JM, Catovsky D, Daniel MT et al. (1991) Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-MO). Br J Haematol 78:325–329PubMedGoogle Scholar
  11. Bernstein ID (2000) Monoclonal antibodies to the myeloid stem cells: therapeutic implications of CMA-676, a humanized anti-CD33 antibody calicheamicin conjugate. Leukemia 14: 474–475PubMedGoogle Scholar
  12. Bitter MA, Le Beau MM, Rowley JD, Larson RA, Golomb HM, Vardiman JW (1987) Associations between morphology, karyotype, and clinical features in myeloid leukemias. Hum Pathol 18:211–225PubMedGoogle Scholar
  13. Bloomfield CD, Goldman A, Hossfeld D, Chapelle A de la (1984) Fourth International Workshop on Chromosomes in Leukemia 1982: Clinical significance of chromosomal abnormalities in acute nonlymphoblastic leukemia. Cancer Genet Cytogenet 11:332–350PubMedGoogle Scholar
  14. Bloomfield CD, Herzig GP, Peterson BA, Wolff SN (1997 a) Long-term survival of patients with acute myeloid leukemia: updated results from two trials evaluating postinduction chemotherapy. Cancer [Suppl 11] 80:2186–2190Google Scholar
  15. Bloomfield CD, Shuma C, Regal L et al. (1997 b) Long-term survival of patients with acute myeloid leukemia: a third follow-up of the Fourth International Workshop on Chromosomes in Leukemia. Cancer [Suppl 11] 80:2191–2198Google Scholar
  16. Bloomfield CD, Lawrence D, Byrd JC et al. (1998) Frequency of prolonged remission duration following high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res 58:4173–4179PubMedGoogle Scholar
  17. Bower M, Parry P, Carter M et al. (1994) Prevalence and clinical correlations of MLL gene rearrangements in AML-M4/M5. Blood 84:3776–3780PubMedGoogle Scholar
  18. Breen TR, Harte PJ (1991) Molecular characterization of the trithorax gene, a positive regulator of homeotic gene expression in Drosophila. Mech Dev 35:113–127PubMedGoogle Scholar
  19. Breen TR, Harte PJ (1993) Trithorax regulates multiple homeotic genes in the bithorax and antennapedia complexes and exerts different tissue-specific, parasegmentspecific and promotor-specific effects on each. Development 117:119–134PubMedGoogle Scholar
  20. Büchner T, Hiddemann W, Wörmann B et al. (1999) Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group. Blood 93:4116–4124PubMedGoogle Scholar
  21. Burnett AK (1999) Tailoring the treatment of acute myeloid leukemia. Curr Opin Oncol 11:14–19PubMedGoogle Scholar
  22. Byrd JC, Weiss RB, Arthur DC et al. (1997) Extramedullar leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461. J Clin Oncol 15:466–475PubMedGoogle Scholar
  23. Byrd JC, Dodge RK, Carroll A et al. (1999) Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered. J Clin Oncol 17:3767–3775PubMedGoogle Scholar
  24. Campana D, Pui CH (1995) Detection of minimal residual disease in acute leukemia: methodologie advances and clinical significance. Blood 85:1416–1434PubMedGoogle Scholar
  25. Campana D, Coustan-Smith E (1996) The use of flow cytometry to detect minimal residual disease in acute leukemia. Eur J Histochem [Suppl 1] 40:39–42Google Scholar
  26. Campana D, Coustan-Smith E (1999) Detection of minimal residual disease in acute leukemia by flow cytometry. Cytometry 38:139–152PubMedGoogle Scholar
  27. Castilla LH, Wijmenga C, Wang Q et al. (1996) Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in gene CBFB-MYH11. Cell 87:687–696PubMedGoogle Scholar
  28. Catovsky D, Matutes E, Buccheri V et al. (1991) A classification of acute leukaemia for the 1990 s. Ann Hematol 62:16–21PubMedGoogle Scholar
  29. Chang KS, Fan YH, Stass SA et al. (1993) Expression of AML1-ETO fusion transcripts and detection of minimal residual disease in t(8;21)-positive acute myeloid leukemia. Oncogene 8:983–988PubMedGoogle Scholar
  30. Chen Z, Guidez F, Rousselot P et al. (1994) PLZF-RAR alpha 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 91:1178–1182PubMedGoogle Scholar
  31. Chen SJ, Wang ZY, Chen Z (1995) Acute promyelocytic leukemia: from clinic to molecular biology. Stem Cells 13:22–31PubMedGoogle Scholar
  32. Cheson BD, Cassileth PA, Head DR et al. (1990) Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol 8:813–819PubMedGoogle Scholar
  33. Claxton DF, Liu P, Hsu HP et al. (1994) Detection of fusion transcripts generated by the inversion 16 chromosome in acute myelogenous leukemia. Blood 83:1750–1756PubMedGoogle Scholar
  34. Corey SJ, Locker J, Oliveri DR et al. (1994) A non-classical translocation involving 17q12 (retinoic receptor alpha) in acute promyelocytic leukemia (APML) with atypical features. Leukemia 8:1350–1353PubMedGoogle Scholar
  35. Costello R, Sainty D, Blaise D, Gastaut JA, Gabert J (1997) Prognosis value of residual disease monitoring by polymerase chain reaction in patients with CBFβ/MYH11-positive acute myeloblastic leukemia. Blood 89:2222–2223PubMedGoogle Scholar
  36. Dastugue N, Payen C, Lafage-Pochitaloff M et al. (1995) Prognostic significance of karyotype in de novo adult acute myeloid leukemia. The BGMT group. Leukemia 9:1491–1498PubMedGoogle Scholar
  37. David G, Alland L, Hong SH, Wong CW, DePinho RA, Dejean A (1998) Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLFZ protein. Oncogene 16:2549–2556PubMedGoogle Scholar
  38. De Thé H, Chomienne C, Lanotte M, Degos L, Dejean A (1990) The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature 347:558–561PubMedGoogle Scholar
  39. De Thé H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A (1991) The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 66:675–684PubMedGoogle Scholar
  40. Domer PH, Fakharzadeh SS, Chen CS et al. (1993) Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product. Proc Natl Acad Sci USA 90:7884–7888PubMedGoogle Scholar
  41. Downing JR, Head DR, Curcio-Brint AM et al. (1993) An AML1/ETO fusion transcript is consistently detected by RNA-based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation. Blood 81:2860–2865PubMedGoogle Scholar
  42. Drexler HG, Thiel E, Ludwig WD (1993) Acute myeloid leukemias expressing lymphoid-associated antigens: diagnostic incidence and prognostic significance. Leukemia 7:489–498PubMedGoogle Scholar
  43. Dyck JA, Maul GG, Miller JH Jr, Chen JD, Kakizuka A, Evans RM (1994) A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell 76:333–343PubMedGoogle Scholar
  44. Elmaagacli AH, Beelen DW, Kroll M, Trzensky S, Stein C, Schaefer UW (1998) Detection of CBFßeta/MYH11 fusion transcripts in patients with inv(16) acute myeloid leukemia after allogeneic bone marrow or peripheral blood progenitor cell transplantation. Bone Marrow Transplant 21:159–166PubMedGoogle Scholar
  45. Engel H, Goodacre A, Keyhani A et al. (1997) Minimal residual disease in acute myelogenous leukaemia and myelodysplastic syndromes: a follow-up of patients in clinical remission. Br J Haematol 99:64–75PubMedGoogle Scholar
  46. Erickson P, Gao J, Chang KS et al. (1992) Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood 80:1825–1831PubMedGoogle Scholar
  47. Estey EH (2000) Treatment of relapsed and refractory acute myelogenous leukemia. Leukemia 14:476–479PubMedGoogle Scholar
  48. Estey EH, Lima M de, Strom S, Pierce S, Freireich EJ, Keating MJ (1997) Long-term follow-up of patients with newly diagnosed acute myeloid leukemia treated at the University of Texas M.D. Anderson Cancer Center. Cancer [Suppl 11] 80:2176–2180Google Scholar
  49. Estey EH, Giles FJ, Kantarjian H et al. (1999) Molecular remissions induced by liposomal-encapsulated all-trans retinoic acid in newly diagnosed acute promyelocytic leukemia. Blood 94:2230–2235PubMedGoogle Scholar
  50. Evans PA, Short MA, Jack AS et al. (1997) Detection and quantitation of the transcripts associated with the inv(16) in presentation and follow-up samples from patients with AML. Leukemia 11:364–369PubMedGoogle Scholar
  51. Exner M, Thalhammer R, Kapiotis S et al. (2000) The „typical“immunophenotype of acute promyelocytic leukemia (APL-M3): does it prove true for the M3-variant? Cytometry 42:106–109PubMedGoogle Scholar
  52. Fang L, Godley LA, Joslin J et al. (2001) Transcript map and comparative analysis of the 1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid diseases with a del(5q). Genomics 71:235–245Google Scholar
  53. Fenaux P, Castaigne S, Dombret H et al. (1992) All-trans retinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases. Blood 80:2176–2181PubMedGoogle Scholar
  54. Fenaux P, Chomienne C, Degos L (1997) Acute promyelocytic leukemia: biology and treatment. Semin Oncol 24:92–102PubMedGoogle Scholar
  55. Fenaux P, Chastang C, Chevret S et al. (1999) A randomized comparison of all-trans retinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood 94:1192–1200PubMedGoogle Scholar
  56. Fenaux P, Chevret S, Guerci A et al. (2000) Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia. European APL Group. Leukemia 14:1371–1377PubMedGoogle Scholar
  57. Fidanza V, Melotti P, Yano T et al. (1996) Double knockout of the ALL-1 gene blocks hematopoietic differentiation in vitro. Cancer Res 56:1179–1183PubMedGoogle Scholar
  58. Folkman J, Watson K, Ingber D, Hanahan D (1989) Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 339:58–61PubMedGoogle Scholar
  59. Fonatsch C, Nowotny H, Pittermann-Höcker E et al. (2001) Amplification of ribosomal RNA genes in acute myeloid leukemia. Genes Chromosomes Cancer 32:11–17PubMedGoogle Scholar
  60. Gaiger A, Schmid D, Heinze G et al. (1998) Detection of the WT1 transcript by RT-PCR in complete remission has no prognostic relevance in de novo acute myeloid leukemia. Leukemia 12:1886–1894PubMedGoogle Scholar
  61. Ganser A, Heil G, Seipelt G et al. (2000) Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with interleukin-2 for myelodysplastic syndromes and high-risk acute myeloid leukemia (AML). Ann Hematol 79:30–35PubMedGoogle Scholar
  62. Gao J, Erickson P, Gardiner K et al. (1991) Isolation of a yeast artificial chromosome spanning the 8;21 translocation breakpoint t(8;21)(q22;q22.3) in acute myelogenous leukemia. Proc Natl Acad Sci USA 88:4882–4886PubMedGoogle Scholar
  63. Giralt S, Khouri I, Champlin R (1999) Non myeloablative „mini transplants“. Cancer Treat Res 101:97–108PubMedGoogle Scholar
  64. Golub TR, Slonim DK, Tamayo P et al. (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286:531–537PubMedGoogle Scholar
  65. Greaves M (1997) Silence of the leukemic clone. N Engl J Med 336:367–369PubMedGoogle Scholar
  66. Greinix HT, Keil F, Brugger SA et al. (1996) Long-term leukemia-free survival after allogeneic marrow transplantation in patients with acute myelogenous leukemia. Ann Hematol 72:53–59PubMedGoogle Scholar
  67. Grignani F, De Matteis S, Nervi C et al. (1998) Fusion proteins of the retinoic receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature 391:815–818PubMedGoogle Scholar
  68. Grimwade D, Walker H, Oliver F et al. (1998) The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. Blood 92:2322–2333PubMedGoogle Scholar
  69. Guerrasio A, Rosso C, Martinelli G et al. (1995) Polyclonal haemopoiesis associated with long-term persistence of the AML1-ETO transcript in patients with FAB M2 acute myeloid leukaemia in continuous clinical remission. Br J Haematol 90:364–368PubMedGoogle Scholar
  70. Hajra A, Collins FS (1995) Structure of the leukemia-associated human CBFB gene. Genomics 26:571–579PubMedGoogle Scholar
  71. Harris NL, Jaffe ES, Diebold J et al. (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 17:3835–3849PubMedGoogle Scholar
  72. He LZ, Guidez F, Tribioli C et al. (1998) Distinct interactions of PML-RARαlpha and PLZF-RAR alpha with compressors determine differential responses to RA in APL. Nat Genet 18:126–135PubMedGoogle Scholar
  73. Hébert J, Cayuela JM, Daniel MT, Berger R, Sigaux F (1994) Detection of minimal residual disease in acute myelomonocytic leukemia with abnormal marrow eosinophils by nested polymerase chain reaction with allele specific amplification. Blood 84:2291–2296PubMedGoogle Scholar
  74. Heim S, Mitelman F (1995) Cancer cytogenetics, 2nd edn. Wiley-Liss, New YorkGoogle Scholar
  75. Hong SH, David G, Wong CW, Dejean A, Privalsky ML (1997) SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha oncoproteins associated with acute promyelocytic leukemia. Proc Natl Acad Sci USA 94:9028–9033PubMedGoogle Scholar
  76. Huang W, Sun GL, Li XS et al. (1993) Acute promyelocytic leukemia: clinical relevance of two major PML-RAR alpha isoforms and detection of minimal residual disease by retrotranscriptase/polymerase chain reaction to predict relapse. Blood 82:1264–1269PubMedGoogle Scholar
  77. Huang ME, Ye YC, Chen SR et al. (1998) Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72:567–572Google Scholar
  78. Hurwitz CA, Raimondi SC, Head D et al. (1992) Distinctive immunophenotypic features of t(8;21)(q22;q22) acute myeloblastic leukemia in children. Blood 80:3182–3188PubMedGoogle Scholar
  79. Hussong JW, Rodgers GM, Shami PJ (2000) Evidence of increased angiogenesis in patients with acute myeloid leukemia. Blood 95:309–313PubMedGoogle Scholar
  80. Jablon S, Kato H (1970) Childhood cancer in relation to prenatal exposure to atomic-bomb radiation. Lancet 2:1000–1003PubMedGoogle Scholar
  81. Jäger U, Laczika K, Scholten C, Mitterbauer M, Novak M, Lechner K (1996) Clinical use of the polymerase chain reaction for diagnosis and management of malignant diseases. Wien Klin Wochenschr 108:634–639PubMedGoogle Scholar
  82. Jurlander J, Caligiuri MA, Ruutu T et al. (1996) Persistence of the AML1/ETO fusion transcript in patients treated with allogeneic bone marrow transplantation for t(8;21) leukemia. Blood 88:2183–2191PubMedGoogle Scholar
  83. Kakizuka A, Miller WH Jr, Umesono K et al. (1991) Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell 66:663–674PubMedGoogle Scholar
  84. Kampmeier P, Spielberger R, Dickstein J, Mick R, Golomb H, Vardiman JW (1994) Increased incidence of second neoplasms in patients treated with interferon alpha 2b for hairy cell leukemia: a clinicopathologic assessment. Blood 83:2931–2938PubMedGoogle Scholar
  85. Kanamaru A, Takemoto Y, Tanimoto M et al. (1995) Alltrans retinoie acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group. Blood 85:1202–1206PubMedGoogle Scholar
  86. Kato H, Yoshimoto Y, Schull WJ (1989) Risk of cancer among children exposed to atomic bomb radiation in utero: a review. IARC Sci Publ 16:365–374Google Scholar
  87. Kennison JA (1993) Transcriptional activation of Drosophila homeotic genes from distant regulatory elements. Trends Genet 9:75–79PubMedGoogle Scholar
  88. Khalidi HS, Medeiros LJ, Chang KL, Brynes RK, Slovak ML, Arber DA (1998) The immunophenotype of adult acute myeloid leukemia: high frequency of lymphoid antigen expression and comparison of immunophenotype, French-American-British classification, and karyotypic abnormalities. Am J Clin Pathol 109:211–220PubMedGoogle Scholar
  89. Klampfer L, Zhang J, Zelenetz AO, Uchida H, Nimer SD (1996) The AML1/ETO fusion protein activates transcription of BCL-2. Proc Natl Acad Sci USA 93:14.059–14.064Google Scholar
  90. Korninger L, Knöbl P, Laczika K et al. (1994) PML-RARα PCR positivity in the bone marrow of patients with APL precedes haematological relapse by 2–3 months. Br J Haematol 88:427–431PubMedGoogle Scholar
  91. Kozu T, Miyoshi H, Shimizu K et al. (1993) Junctions of the AML1/MTG8(ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction. Blood 82:1270–1276PubMedGoogle Scholar
  92. Krauter J, Hoellge W, Wattjes M et al. (1999) Real time PCR for the detection and quantification of CBFβ/MYH11 fusion transcripts in inv(16) positive AML. Blood [Suppl 1] 94:207bGoogle Scholar
  93. Kusec R, Laczika K, Knöbl P et al. (1994) AML1/ETO fusion mRNA can be detected in remission blood samples of all patients with t(8;21) acute myeloid leukemia after chemotherapy or autologous bone marrow transplantation. Leukemia 8:735–739PubMedGoogle Scholar
  94. Kwok S, Higuchi R (1989) Avoiding false positives with PCR. Nature 339:237–238PubMedGoogle Scholar
  95. Laczika K, Mitterbauer G, Knoebl P et al. (1994) Rapid achievement of PML-RARα PCR-negativity by combined treatment with all-trans retinoic acid and chemotherapy: a pilot study. Leukemia 8:1–5PubMedGoogle Scholar
  96. Laczika K, Novak M, Hilgarth B et al. (1998) Competitive CBFβeta/MYH11 reverse-transcriptase polymerase chain reaction for quantitative assessment of minimal residual disease during postremission therapy in acute myeloid leukemia with inversion(16): a pilot study. J Clin Oncol 16:1519–1525PubMedGoogle Scholar
  97. Laczika K, Mitterbauer G, Weltermann A et al. (2000) Prolonged third remission in a patient with acute promyelocytic leukemia after consolidation chemotherapy with intermittent intermediate dose Ara-C and maintenance with intermittent all-trans retinoic acid (ATRA). Leuk Lymphoma 36:625–629PubMedGoogle Scholar
  98. Lai F, Godley LA, Joslin J et al. (2001) Transcript map and comparative analysis of the 1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid diseases with a del(5q). Genomics 71:235–245PubMedGoogle Scholar
  99. Lamy T, Goasguen JE, Mordelet E et al. (1994) P-glycoprotein (P-170) and CD34 expression in adult acute myeloid leukemia (AML). Leukemia 8:1879–1883PubMedGoogle Scholar
  100. Langabeer SE, Walker H, Gale RE et al. (1997) Frequency of CBFβeta/MYH11 fusion transcripts in patients entered into UK MRC AML trials. Br J Haematol 96:736–739PubMedGoogle Scholar
  101. Lay ton DM, Mufti GJ (1986) Myelodysplastic syndromes: their history, evolution and relation to acute myeloid leukaemia. Blut 53:423–436Google Scholar
  102. Le Beau MM, Larson RA, Bitter MA, Vardiman JW, Golomb HM, Rowley JD (1983) Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia. A unique cytogenetic-clinicopathological association. N Engl J Med 309:630–636PubMedGoogle Scholar
  103. Legrand O, Per rot JY, Simonin G et al. (1998) Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression. Br J Haematol 100:147–155PubMedGoogle Scholar
  104. Leone G, Mele L, Pulsoni A, Equitani F, Pagano L (1999) The incidence of secondary leukemias. Haematologica 84:937–945PubMedGoogle Scholar
  105. Levine EG, Bloomfield CD (1992) Leukemias and myelodysplastic syndromes secondary to drug, radiation, and environmental exposure. Semin Oncol 19:47–84PubMedGoogle Scholar
  106. Lewis EB (1978) A gene complex controlling segmentation in Drosophila. Nature 276:565–570PubMedGoogle Scholar
  107. Lin RJ, Nagy L, Inoue S, Shao W, Miller WH Jr, Evans RM (1998) Role of the histone deacetylase complex in acute promyelocytic leukemia. Nature 391:811–814PubMedGoogle Scholar
  108. Liu P, Tarlé SA, Hajra A et al. (1993) Fusion between transcription factor CBFβ/PEBP2β and myosin heavy chain in acute myeloid leukemia. Science 261:1041–1044PubMedGoogle Scholar
  109. Liu PP, Hajra A, Wijmenga C, Collins FS (1995) Molecular pathogenesis of the chromosome 16 inversion in the M4Eo subtype of acute myeloid leukemia. Blood 85:2289–2302PubMedGoogle Scholar
  110. Liu Yin JA (1999) Detection of minimal residual disease in acute myeloid leukemia: methodologies, clinical and biological significance. Br J Haematol 106:578–590Google Scholar
  111. Lo YM, Mehal WZ, Fleming KA (1988) False-positive results and the polymerase chain reaction. Lancet 2:679PubMedGoogle Scholar
  112. Lockhart DJ, Dong H, Byrne MC et al. (1996) Expression monitoring by hybridization to high-density oligonucleotide arrays. Nat Biotechnol 14:1675–1680PubMedGoogle Scholar
  113. LoCoco F, Diverio D, Awisati G et al. (1999) Therapy of molecular relapse in acute promyelocytic leukemia. Blood 94:2225–2229Google Scholar
  114. Look AT (1997) Oncogenic transcription factors in the human acute leukemias. Science 278:1059–1064PubMedGoogle Scholar
  115. Ma Q, Alder H, Nelson KK et al. (1993) Analysis of the murine All-1 gene reveals conserved domains with human ALL-1 and identifies a motif shared with DNA methyltransferases. Proc Natl Acad Sci USA 90:6350–6354PubMedGoogle Scholar
  116. Mandelli F, Diverio D, Awisati G et al. (1997) Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood 90:1014–1021PubMedGoogle Scholar
  117. Marcucci G, Caligiuri MA, Bloomfield CD (1997) Defining the „absence“of the CBFβ/MYH11 fusion transcript in patients with acute myeloid leukemia and inversion of chromosome 16 to predict long-term complete remission: a call for definitions. Blood 90:5022–5025PubMedGoogle Scholar
  118. Marcucci G, Livak KJ, Bi W, Strout MP, Bloomfield CD, Caligiuri MA (1998) Detection of minimal residual disease in patients with AML1/ETO-associated acute myeloid leukemia using a novel quantitative reverse transcription polymerase chain reaction assay. Leukemia 12:1482–1489PubMedGoogle Scholar
  119. Marcucci G, Caligiuri MA, Maghraby EA et al. (1999) Quantification of CBFβ/MYH11 transcripts in inv(16) acute myeloid leukemia (AML) by real time RT-PCR. Blood [Suppl 1] 94:740aGoogle Scholar
  120. Martin G, Barragan E, Bolufer P et al. (2000) Relevance of presenting white blood cell count and kinetics of molecular remission in the prognosis of acute myeloid leukemia with CBFβ/MYH11 rearrangement. Haematologica 85:699–703PubMedGoogle Scholar
  121. Martinelli G, Ottaviani E, Testoni N, Montefusco V, Pastano R, Tura S (2000) Long-term disease-free acute myeloblastic leukemia with inv(16) is associated with PCR undetectable CBFβ/MYH11 transcript. Haematologica 8:552–555Google Scholar
  122. Martinez-Climent JA, Espinosa R 3rd, Thirman MJ, Le Beau MM, Rowley JD (1995) Abnormalities of chromosome band 11q23 and the MLL gene in pediatric myelomonocytic and monoblastic leukemias. Identification of the t(9;ll) as an indicator of long survival. J Pediatr Hematol Oncol 17:277–283PubMedGoogle Scholar
  123. Mayer RJ, Davis RB, Schiffer CA et al. (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 331:896–903PubMedGoogle Scholar
  124. Mazo AM, Huang DH, Mozer BA, Dawid IB (1990) The trithorax gene, a trans-acting regulator of the bithorax complex in Drosophilay encodes a protein with zinc-binding domains. Proc Natl Acad Sci USA 87:2112–2116PubMedGoogle Scholar
  125. Meloni G, Diverio D, Vignetti M et al. (1997) Autologous bone marrow transplantation for acute promyelocytic leukemia in second remission: prognostic relevance of pretransplant minimal residual disease assessment by reverse-transcription polymerase chain reaction of the PML/RAR alpha fusion gene. Blood 90:1321–1325PubMedGoogle Scholar
  126. Meyers S, Downing JR, Hiebert SW (1993) Identification of AML1 and the t(8;21) translocation protein (AML1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA-binding and protein-protein interactions. Mol Cell Biol 13:6336–6345PubMedGoogle Scholar
  127. Meyers S, Lenny N, Hiebert SW (1995) The t(8;21) fusion protein interferes with AML-1B-dependent transcriptional activation. Mol Cell Biol 15:1974–1982PubMedGoogle Scholar
  128. Michallet M, Thomas X, Vernant JP et al. (2000) Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societe Francaise de Greffe de Moelle (SFGM). Bone Marrow Transplant 26:1157–1163PubMedGoogle Scholar
  129. Miller WH Jr, Levine K, DeBlasio A, Frankel SR, Dmitrovsky E, Warrell RP Jr (1993) Detection of minimal residual disease in acute promyelocytic leukemia by a reverse transcription polymerase chain reaction assay for the PML/RAR-alpha fusion mRNA. Blood 82:1689–1694PubMedGoogle Scholar
  130. Mitterbauer M, Kusec R, Schwarzinger I, Haas OA, Lechner K, Jaeger U (1998) Comparison of karyotype analysis and RT-PCR for AML1/ETO in 204 unselected patients with AML. Ann Hematol 76:139–143PubMedGoogle Scholar
  131. Mitterbauer G, Zimmer C, Fonatsch C et al. (1999) Monitoring of minimal residual leukemia in patients with MLL-AF9 positive acute myeloid leukemia by RT-PCR. Leukemia 13:1519–1524PubMedGoogle Scholar
  132. Mitterbauer M, Laczika K, Novak M et al. (2000 a) High concordance of karyotype analysis and RT-PCR for CBF beta/ MYH11 in unselected patients with acute myeloid leukemia. A single center study. Am J Clin Pathol 113:406–410PubMedGoogle Scholar
  133. Mitterbauer G, Zimmer C, Pirc-Danoewinata H et al. (2000 b) Monitoring of minimal residual disease in patients with MLL-AF6-positive acute myeloid leukemia by reverse transcriptase polymerase chain reaction. Br J Haematol 109:622–628PubMedGoogle Scholar
  134. Miwa H, Kita K, Nishii K et al. (1993) Expression of MDR1 gene in acute leukemia cells: association with CD7+ acute myeloblastic leukemia/acute lymphoblastic leukemia. Blood 82:3445–3451PubMedGoogle Scholar
  135. Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M (1991) t(8;21) breakpoints on chromosome 21 in acute myeloid leukaemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci USA 88: 10431–10434PubMedGoogle Scholar
  136. Mrózek K, Heinonen K, Chapelle A de la, Bloomfield CD (1997 a) Clinical significance of cytogenetics in acute myeloid leukemias. Semin Oncol 24:17–31PubMedGoogle Scholar
  137. Mrózek K, Heinonen K, Lawrence D et al. (1997 b) Adult patients with de novo acute myeloid leukemia and t(9;11)(p22;q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study. Blood 90:4532–4538PubMedGoogle Scholar
  138. Mrózek K, Heinonen K, Bloomfield CD (2001) Clinical importance of cytogenetics in acute myeloid leukemia. Baillieres Best Pract Res Clin Haematol 14:19–47Google Scholar
  139. Nucifora G, Birn DJ, Erickson P et al. (1993 a) Detection of DNA rearrangements in the AML1 and ETO loci and of an AML1/ETO fusion mRNA in patients with t(8;21) acute myeloid leukemia. Blood 81:883–888PubMedGoogle Scholar
  140. Nucifora G, Larson RA, Rowley JD (1993 b) Persistence of the 8;21 translocation in patients with acute myeloid leukemia type M2 in long-term remission. Blood 82:712–715PubMedGoogle Scholar
  141. Nucifora G, Dickstein JI, Torbenson V, Roulston D, Rowley JD, Vardiman JW (1994) Correlation between cell morphology and expression of the AML1/ETO chimeric transcript in patients with acute myeloid leukemia without the t(8;21). Leukemia 8:1533–1538PubMedGoogle Scholar
  142. Okuda T, Deursen J van, Hiebert SW, Grosveld G, Downing JR (1996) AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84:321–330PubMedGoogle Scholar
  143. Okuda T, Cai Z, Yang S et al. (1998) Expression of a knocked- in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors. Blood 91:3134–3143PubMedGoogle Scholar
  144. Oosterveld M, Witte T de (2000) Intensive treatment strategies in patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia. Blood Rev 14:182–189PubMedGoogle Scholar
  145. Padro T, Ruiz S, Bieker R et al. (2000) Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia. Blood 95:2637–2644PubMedGoogle Scholar
  146. Paietta E (1995) Proposals for the immunological classification of acute leukemias. Leukemia 9:2147–2148PubMedGoogle Scholar
  147. Paietta E, Wiernik PH, Andersen J, Bennett J, Yunis J (1993) Acute myeloid leukemia M4 with inv(16) (p13q22) exhibits a specific immunophenotype with CD2 expression. Blood 82:2595PubMedGoogle Scholar
  148. Paietta E, Andersen J, Wiernik PH (1996) A new approach to analyzing the utility of immunophenotyping for predicting clinical outcome in acute leukemia. Eastern Cooperative Oncology Group. Leukemia 10:1–4PubMedGoogle Scholar
  149. Pallisgaard N, Hokland P, Riishoj DC, Pedersen B, Jorgensen P (1998) Multiplex reverse transcription-polymerase chain reaction and chromosomal aberrations in acute myeloid leukemia. Blood 92:574–588PubMedGoogle Scholar
  150. Pedersen-Bjergaard J, Rowley JD (1994) The balanced and the unbalanced chromosome aberrations of acute myeloid leukemia may develop in different ways and may contribute differently to malignant transformation. Blood 83:2780–2786PubMedGoogle Scholar
  151. Pedersen-Bjergaard J, Andersen MK (1998 a) Secondary or therapy-related MDS and AML and their chromosome aberrations: important to study but difficult to establish causality. Haematologica 83:481–482PubMedGoogle Scholar
  152. Pedersen-Bjergaard J, Andersen MK, Johansson B (1998 b) Balanced chromosome aberrations in leukemias following chemotherapy with DNA-topoisomerase II inhibitors. J Clin Oncol 16:1897–1898PubMedGoogle Scholar
  153. Poirel H, Radford-Weiss I, Rack K et al. (1995) Detection of chromosome 16 CBFβ-MYH11 fusion transcript in myelomonocytic leukemias. Blood 85:1313–1322PubMedGoogle Scholar
  154. Pui CH, Behm FG, Raimondi SC et al. (1989) Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia. N Engl J Med 321:136–142PubMedGoogle Scholar
  155. Reeves R, Nissen MS (1990) The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA-structure. J Biol Chem 265:8573–8582PubMedGoogle Scholar
  156. Rege K, Swansbury GJ, Atra AA et al. (2000) Disease features in acute myeloid leukemia with t(8;21)(q22;q22). Influence of age, secondary karyotype abnormalities, CD 19 status, and extramedullary leukemia on survival. Leuk Lymphoma 404:67–77Google Scholar
  157. Rimsza LM, Kopecky KJ, Ruschulte J et al. (2000) Microsatellite instability is not a defining genetic feature of acute myeloid leukemogenesis in adults: results of a retrospective study of 132 patients and review of the literature. Leukemia 14:1044–1051PubMedGoogle Scholar
  158. Rinsky RA, Smith AB, Hornung R et al. (1987) Benzene and leukemia. An epidemiologic risk assessment. N Engl J Med 316:1044–1050PubMedGoogle Scholar
  159. Rowley JD (1992) The der(11) chromosome contains the critical breakpoint junction in the 4;11, 9;11, and the 11;19 translocations in acute leukemia. Genes Chromosomes Cancer 5:254–266Google Scholar
  160. Rowley JD (2000) Cytogenetic analysis in leukemia and lymphoma: an introduction. Semin Hematol 37:315–319PubMedGoogle Scholar
  161. Rozenblatt-Rosen O, Rozovskaia T, Burakov D et al. (1998) The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex. Proc Natl Acad Sci USA 95:4152–4157PubMedGoogle Scholar
  162. San Miguel JF, Martinez A, Macedo A et al. (1997) Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. Blood 90:2465–2470PubMedGoogle Scholar
  163. Sanz MA, LoCoco F, Martin G et al. (2000) Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood 96:1247–1253PubMedGoogle Scholar
  164. Sasaki K, Yagi H, Bronson RT et al. (1996) Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor beta. Proc Natl Acad Sci USA 3:12.359–12.363Google Scholar
  165. Saunders MJ, Tobal K, Yin JA (1994) Detection of t(8;21) by reverse transcriptase polymerase chain reaction in patients in remission of acute myeloid leukaemia type M2 after chemotherapy or bone marrow transplantation. Leuk Res 18:891–895PubMedGoogle Scholar
  166. Schena M, Shalon M, Heller R, Chai QA, Brown PO, Davis RW (1996) Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. Proc Natl Acad Sci USA 93:10.614–10.619Google Scholar
  167. Schmid D, Heinze G, Linnerth B et al. (1997) Prognostic significance of WT1 gene expression at diagnosis in adult de novo acute myeloid leukemia. Leukemia 11:639–643PubMedGoogle Scholar
  168. Schoch C, Haase D, Haferlach T et al. (1996) Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor. Leukemia 10: 1288–1295PubMedGoogle Scholar
  169. Second MIC Cooperative Study Group (1988) Morphologic, immunologic and cytogenetic (MIC) working classification of the acute myeloid leukemias. Br J Haematol 68:487–497Google Scholar
  170. Sedkov Y, Tillib S, Mizrokhi L, Mazo A (1994) The bithorax complex is regulated by trithorax earlier during Drosophila embryogenesis than is the antennapedia complex, correlating with a bithorax-like expression pattern of distinct early trithorax transcripts. Development 120:1907–1917PubMedGoogle Scholar
  171. Sievers EL, Appelbaum FR, Spielberger RT et al. (1999) Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calcheamicin immunoconjugate. Blood 93: 3678–3684PubMedGoogle Scholar
  172. Slovak ML, Kopecky KJ, Cassileth PA et al. (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood 96: 4075–4083PubMedGoogle Scholar
  173. Smith MA, McCaffrey RP, Karp JE (1996) The secondary leukemias: challenges and research directions. J Natl Cancer Inst 88:407–418PubMedGoogle Scholar
  174. Stindl R, Fiegl M, Regele H, Gisslinger H, Breitenseher MJ, Fonatsch C (1998) Alveolar rhabdomyosarcoma in a 68-year-old patient identified by cytogenetic analysis of bone marrow. Cancer Genet Cytogenet 107:43–47PubMedGoogle Scholar
  175. Stoiser B, Knöbl P, Fonatsch C et al. (2000) Prognosis of patients with a second relapse of acute myeloid leukaemia. Leukemia 14:2059–2063PubMedGoogle Scholar
  176. Streubel B, Valent P, Jäger U et al. (2000) Amplification of the MLL gene on double minutes, a homogeneously staining region, and ring chromosomes in five patients with acute myeloid leukemia or myelodysplastic syndrome. Genes Chromosomes Cancer 27:380–386PubMedGoogle Scholar
  177. Strout MP, Marcucci G, Caligiuri MA, Bloomfield CD (1999) Core-binding factor (CBF) and MLL-associated primary acute myeloid leukemia: biology and clinical implications. Ann Hematol 78:251–264PubMedGoogle Scholar
  178. Tallman MS, Andersen JW, Schiffer CA et al. (1997) All-trans retinoic acid in acute promyelocytic leukemia. N Engl J Med 337:1021–1028PubMedGoogle Scholar
  179. Tallmann MS, Andersen JW, Schiffer CA et al. (2000) Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood 95:90–95Google Scholar
  180. Tamayo P, Slonim D, Mesirov J et al. (1999) Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation. Proc Nati Acad Sci USA 96:2907–2912Google Scholar
  181. Taylor PR, Reid MM, Stark AN, Bown N, Hamilton PJ, Proctor SJ (1995) De novo acute myeloid leukaemia in patients over 55-years-old: a population-based study of incidence, treatment and outcome. Northern Region Haematology Group. Leukemia 9:231–237PubMedGoogle Scholar
  182. Taylor CG, Stasi R, Bastianelli C et al. (1996) Diagnosis and classification of the acute leukemias: recent advances and controversial issues. Hematopathol Mol Hematol 10:1–38PubMedGoogle Scholar
  183. Thalhammer F, Geissler K, Jäger U et al. (1996) Duration of second complete remission in patients with acute myeloid leukemia treated with chemotherapy: a retrospective single-center study. Ann Hematol 72:216–222PubMedGoogle Scholar
  184. Thirman MJ, Gill HJ, Burnett RC et al. (1993) Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med 329:909–914PubMedGoogle Scholar
  185. Tobal K, Johnson PRE, Saunders MJ, Harrison CJ, Liu Yin JA (1995) Detection of CBFβ/MYH11 transcripts in patients with inversion and other abnormalities of chromosome 16 at presentation and remission. Br J Haematol 91:104–108PubMedGoogle Scholar
  186. Tobal K, Newton J, Macheta M et al. (2000) Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse. Blood 95:815–819PubMedGoogle Scholar
  187. Van der Reijden BA, Dauwerse JG, Wessels JW et al. (1993) A gene for a myosin peptide is disrupted by the inv(16) (p13q22) in acute nonlymphocytic leukemia M4Eo. Blood 82:2948–2952PubMedGoogle Scholar
  188. Van der Reijden BA, Lombardo M, Dauwerse HG et al. (1995) RT-PCR diagnosis of patients with acute nonlymphocytic leukemia and inv(16)(p13q22) and identification of new alternative splicing in CBFB-MYH11 transcripts. Blood 86:277–282PubMedGoogle Scholar
  189. Venditti A, Buccisano F, Del PG et al. (2000) Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood 96:3948–3952PubMedGoogle Scholar
  190. Wang Q, Stacy T, Binder M, Marin-Padilla M, Sharpe AH, Speck NA (1996 a) Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci USA 93:3444–3449PubMedGoogle Scholar
  191. Wang Q, Stacy T, Miller JD et al. (1996b) The CBFβ subunit is essential for CBFalpha2 (AML1) function in vivo. Cell 87:697–708PubMedGoogle Scholar
  192. Warrell RP Jr, De Thé H, Wang ZY, Degos L (1993) Acute promyelocytic leukemia. N Engl J Med 329:177–189PubMedGoogle Scholar
  193. Warrell RP Jr, Maslak P, Eardley A, Heller G, Miller WH Jr, Frankel SR (1994) Treatment of acute promyelocytic leukemia with all-trans retinoic acid: an update of the New York experience. Leukemia 8:929–933PubMedGoogle Scholar
  194. Wattjes MP, Krauter J, Nagel S, Heidenreich O, Ganser A, Heil G (2000) Comparison of nested competitive RT-PCR and real-time RT-PCR for the detection and quantification of AML1/MTG8 fusion transcripts in t(8;21) positive acute myelogenous leukemia. Leukemia 14:329–335PubMedGoogle Scholar
  195. Westendorf JJ, Yamamoto CM, Lenny N, Downing JR, Selsted ME, Hiebert SW (1998) The t(8;21) fusion product, AML1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation. Mol Cell Biol 18:322–333PubMedGoogle Scholar
  196. Wieser R, Schreiner U, Pirc-Danoewinata H et al. (2001) Interphase fluorescence in situ hybridization assay for the detection of 3q21 rearrangements in myeloid malignancies. Genes Chromosomes Cancer 32: 373–380PubMedGoogle Scholar
  197. Willman CL (1999) Acute leukemias: a paradigm for the integration of new technologies in diagnosis and classification. Mod Pathol 12:218–228PubMedGoogle Scholar
  198. Wörmann B, Safford M, Konemann S, Büchner T, Hiddemann W, Terstappen LW (1993) Detection of aberrant antigen expression in acute myeloid leukemia by multiparameter flow cytometry. Recent Results Cancer Res 131:185–196PubMedGoogle Scholar
  199. Yergeau DA, Hetherington CJ, Wang Q et al. (1997) Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1-ETO fusion gene. Nat Genet 15:303–306PubMedGoogle Scholar
  200. Yu BD, Hess JL, Horning SE, Brown GA, Korsmeyer SJ (1995) Altered HOX expression and segmental identity in Mil-mutant mice. Nature 378:505–508PubMedGoogle Scholar
  201. Zhang Z, Nakamura M, Taniguchi E, Shan L, Yokoi T, Kakudo K (1997) A simple approach to single-cell microdissection and molecular analysis. Anal Quant Cytol Histol 19:514–518PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • Christa Fonatsch
  • Ilse Schwarzinger
  • Gerlinde Mitterbauer
  • Ulrich Jäger
  • Rotraud Wieser
  • Christine Mannhalter
  • Klaus Lechner

There are no affiliations available

Personalised recommendations