Advertisement

Akute lymphoblastische Leukämie (ALL) im Kindesalter

  • Arndt Borkhardt
Part of the Molekulare Medizin book series (MOLMED)

Zusammenfassung

Die akute lymphoblastische Leukämie (ALL) ist durch die ungehemmte, klonale Proliferation unreifer lymphoider Zellen im Knochenmark gekennzeichnet. Sekundär können alle extramedullären Organe, z.B. Lymphknoten, Milz, Leber, Niere, Hoden oder das zentrale Nervensystem, durch die Blastenpopulation infiltriert werden. Die maligne Transformation kann auf jeder Stufe der frühen B-oder T-Zell-Differenzierung entstehen. Dies erklärt die Heterogenität der ALL bzw. die besonders charakterisierbaren ALL-Untertypen. Ohne zytotoxische Chemotherapie führt jede ALL obligat in wenigen Wochen infolge Knochenmarkinsuffizienz (Anämie, Thrombozytopenie, Granulozytopenie) durch Blutungen oder Infektionen zum Tod.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. Barrios C, Brawand P, Berney M, Brandt C, Lambert P-H, Siegrist C-A (1996) Neonatal and early life immune responses to various forms of vaccine antigens quantitatively differ from adult responses: predominance of Th2-biased pattern which persists after adult boosting. Eur J Immunol 26:1489–1496PubMedCrossRefGoogle Scholar
  2. Behm FG, Raimondi SC, Frestedt JL et al. (1996) Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age. Blood 87:2870–2877PubMedGoogle Scholar
  3. Blackwood EM, Eisenman RN (1991) A helix-loop-helix zipper protein that forms a sequence-specific DNA binding complex with myc. Science 251:1211–1213PubMedCrossRefGoogle Scholar
  4. Borgmann A, Hartmann R, Schmid H et al. (1995) Isolated extramedullary relapse in children with acute lymphoblastic leukemia: a comparison between treatment results of chemotherapy and bone marrow transplantation. Bone Marrow Transplant 15:515–521PubMedGoogle Scholar
  5. Borkhardt A, Cazzaniga G, Viehmann S et al. (1997) Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastoc leukemia (ALL) enrolled in the German and Italien multicenter therapy trials. Blood 90:571–577PubMedGoogle Scholar
  6. Borkhardt A, Harbott J, Lampert F (1999) Biology and clinical significance of the TEL/AML1 rearrangement. Curr OpinPediatr 11:33–38Google Scholar
  7. Caspersson T, Zech L, Johansson C (1970) Differential binding of alkylating fluorochromes in human chromosomes. Exp Cell Res 60:315–319PubMedCrossRefGoogle Scholar
  8. Cimino G, Rapanotti MC, Rivolta A et al. (1995) Prognostic relevance of ALL-1 gene rearrangement in infant acute leukemias. Leukemia 9:391–395PubMedGoogle Scholar
  9. Cimino G, Rapanotti MC, Sprovieri T, Elia L (1998) ALL1 gene alterations in acute leukemia: biological and clinical aspects. Haematologica 83:350–357PubMedGoogle Scholar
  10. Cui XM, Vivo I de, Slany R, Miyamoto A, Firestein R, Cleary ML (1998) Association of SET domain and myotubularin-related proteins modulates growth control. Nat Genet 18:331–337PubMedCrossRefGoogle Scholar
  11. Cutler S J, Axtell L, Heise H (1967) Ten thousand cases of leukemia: 1940–1962. J Natl Cancer Inst 39:993–999PubMedGoogle Scholar
  12. Daley GQ, Etten RA van, Baltimore D (1990) Induction of chronic myelogenous leukemia in mice by p210BCR-ABL gene of the Philadelphia chromosome. Science 247:824–830PubMedCrossRefGoogle Scholar
  13. Danial NN, Rothman P (2000) JAK-STAT signaling activated by Abl oncogenes. Oncogene 19:2523–2531PubMedCrossRefGoogle Scholar
  14. DiMartino JF, Cleary ML (1999) MLL rearrangements in haematological malignancies: lessons from clinical and biological studies. Br J Haematol 106:614–626PubMedCrossRefGoogle Scholar
  15. Dobson CL, Warren AJ, Pannell R, Forster A, Rabbitts TH (2000) Tumorigenesis in mice with a fusion of the leukaemia oncogene Mil and the bacterial lacZ gene. EMBO J 19:843–851PubMedCrossRefGoogle Scholar
  16. Feer E, Finkelstein H, Ibrahim J et al. (1921) Lehrbuch der Kinderheilkunde. Fischer, JenaGoogle Scholar
  17. Fletcher JA, Lynch EA, Kimball VM, Donnelly M, Tantravahi R, Sallan SE (1991) Translocation (9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia. Blood 77:435–439PubMedGoogle Scholar
  18. Ford AM, Ridge SA, Cabrera ME et al. (1993) In utero rearrangement in the trithorax-related onogene in infant leukaemias. Nature 363:358–360PubMedCrossRefGoogle Scholar
  19. Gale KB, Ford AM, Repp R et al. (1997) Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA 94:13.950–13.954Google Scholar
  20. Gaston I, Stenberg PE, Bhat A, Druker BJ (2000) Abl kinase but not PI3-kinase links to the cytoskeletal defects in Bcr-Abl transformed cells. Exp Hematol 28:77–86PubMedCrossRefGoogle Scholar
  21. Golub TR, Barker GF, Lovett M, Gilliland DG (1994) Fusion of the PDGF receptor b to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 77:307–316PubMedCrossRefGoogle Scholar
  22. Golub TR, Barker GF, Bohlander SK et al. (1995) Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci USA 92:4917–4921PubMedCrossRefGoogle Scholar
  23. Götz G, Weh H-J, Walter TA et al. (1992) Clinical and prognostic significance of the Philadelphia chromosome in adult patients with acute lymphoblastic leukemia. Ann Hematol 64:97–100PubMedCrossRefGoogle Scholar
  24. Greaves MF (1990) The Sellafield childhood leukemia cluster: are germline mutations responsible. Leukemia 4:391–396PubMedGoogle Scholar
  25. Greaves MF (1991) Models of childhood acute lymphoblastic leukaemia. Leukemia 5:819–821PubMedGoogle Scholar
  26. Greaves MF (1997) Aetiology of acute leukaemia. Lancet 349:344–349PubMedCrossRefGoogle Scholar
  27. Greaves M (1999) Molecular genetics, natural history and the demise of childhood leukaemia. Eur J Cancer Part A 35:173–185CrossRefGoogle Scholar
  28. Greaves MF, Brown G, Rapson N, Lister TA (1975) Antisera to acute lymphoblastic leukemia cells. Clin Immunol Immunopathol 4:67–84PubMedCrossRefGoogle Scholar
  29. Guidez F, Petrie K, Ford AM et al. (2000) Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein. Blood 96:2557–2561PubMedGoogle Scholar
  30. Harbott J (1993) Chromosomenaberrationen bei akuten Leukämien im Kindesalter. Enke, StuttgartGoogle Scholar
  31. Harbott J, Budde M, Creutzig U et al. (1987) Prognostic meaning of chromosome aberrations in acute lymphocytic leukemia and acute nonlymphocytic leukemia patients of the BFM study group. Haematol Blood Transfus 30:497–503PubMedGoogle Scholar
  32. Harbott J, Ritterbach J, Janka-Schaub G et al. (1990) Cytogenetics of childhood acute lymphoblastic leukemia in multicenter trials. Haematol Blood Transfus 33:451–458PubMedGoogle Scholar
  33. Harbott J, Ritterbach J, Ludwig WD, Bartram CR, Reiter A, Lampert F (1991) Clinical significance of cytogenetic studies in childhood ALL: Experience of the ALL-BFM trials. In: NN (ed) Recent results in cancer research. Springer, Berlin Heidelberg New YorkGoogle Scholar
  34. Hertl M, Landbeck G (1969) Leukämie bei Kindern. Thieme, Stuttgart New YorkGoogle Scholar
  35. Hiebert SW, Sun WH, Davis JN et al. (1996) The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription. Mol Cell Biol 16:1349–1355PubMedGoogle Scholar
  36. Hong SL, O’Hagan RC, Hou H Jr, Horner JW II, Lee HW, DePinho RA (2000) Essential role for Max in early embryonic growth and development. Genes Dev 14:17–22Google Scholar
  37. Hoogerbrugge PM, Gerritsen EJ, Berg VD den et al. (1995) Case-control analysis of allogeneic bone marrow transplantation versus maintenance chemotherapy for relapsed ALL in children. Bone Marrow Transplant 15:255–259PubMedGoogle Scholar
  38. Hunger SP (1996) Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis. Blood 87:1211–1224PubMedGoogle Scholar
  39. IMSD (2000) Jahresbericht 1999 des Deutschen Kinderkrebsregisters. Johannes-Gutenberg-Universität, MainzGoogle Scholar
  40. Kaspers GJL, Veerman AJP, Pieters R et al. (1997) In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood 90:2723–2729PubMedGoogle Scholar
  41. Kato GJ, Dang CV (1992) Function of the c-Myc oncoprotein. FASEB J 6:3065–3072PubMedGoogle Scholar
  42. Kelliher MA, McLaughlin J, Witte ON, Rosenberg N (1990) Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci USA 87:6649–6653PubMedCrossRefGoogle Scholar
  43. Kelliher M, Knott A, McLaughlin J, Witte ON, Rosenberg N (1991) Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. Mol Cell Biol 11:4710–4716PubMedGoogle Scholar
  44. Kim-Rouille MH, MacGregor A, Wiedemann LM, Greaves MF, Navarrete C (1999) MLL-AF4 gene fusions in normal newborns. Blood 93:1107–1108PubMedGoogle Scholar
  45. Kobayashi Y, Hayashi Y, Ozawa K, Asano S (1995) HRX gene rearrangement in secondary acute lymphoblastic leukemia. Leuk Lymphoma 17:391–399PubMedCrossRefGoogle Scholar
  46. Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497PubMedCrossRefGoogle Scholar
  47. Kulozik AE, Hentze MW, Hagemeier C, Bartram CR (2000) Molekulare Medizin, de Gruyter, Berlin New YorkCrossRefGoogle Scholar
  48. Lampert F, Henze G, Langermann HJ, Schellong G, Gadner H, Riehm H (1984) Acute lymphoblastic leukemia: current status of therapy in children. Recent Results Cancer Res 93:159–181PubMedGoogle Scholar
  49. Lavau C, Szilvassy SJ, Slany R, Cleary ML (1997) Immortalization and leukemic transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL. EMBO J 16:4226–4237PubMedCrossRefGoogle Scholar
  50. Lestingi TM, Hooberman AL (1993) Philadelphia chromosome positive acute lymphoblastic leukemia. Hematol Oncol Clin North Am 7:161–175PubMedGoogle Scholar
  51. Ludwig WD, Thiel E (1993) Diagnosis of acute leukemia with morphologic, immunologic and cytogenetic procedures. Internist 34:498–510PubMedGoogle Scholar
  52. Ludwig WD, Harbott J, Bartram CR et al. (1991) Incidence, biologic features, and clinical impact of myeloid-antigen expression in childhood ALL (MY+ALL). Haematologica 76:33Google Scholar
  53. Ludwig WD, Raghavachar A, Thiel E (1994) Immunophenotypic classification of acute lymphoblastic leukaemia. Baillieres Clin Haematol 7:235–262PubMedCrossRefGoogle Scholar
  54. Mahon FX, Deininger MW, Schultheis B et al. (2000) Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood 96:1070–1079PubMedGoogle Scholar
  55. Maurer J, Janssen JWG, Thiel E et al. (1991) Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by the polymerase chain reaktion. Lancet 337:1055–1058PubMedCrossRefGoogle Scholar
  56. McNally RJ, Birch JM, Taylor GM, Eden OB (2000) Incidence of childhood precursor B-cell acute lymphoblastic leukaemia in north-west England. Lancet 356:485–486PubMedCrossRefGoogle Scholar
  57. Melo JV (1996 a) The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. Blood 88:2375–2384PubMedGoogle Scholar
  58. Melo JV (1996 b) The molecular biology of chronic myeloid leukaemia. Leukemia 10:S4–S9Google Scholar
  59. Michaelis J, Kaletsch U, Burkart W, Grosche B (1997) Infant leukaemia after the Chernobyl accident. Nature 387:246–247PubMedCrossRefGoogle Scholar
  60. Miller DR, Miller LP (1990) Acute lymphoblastic leukemia in children: an update of clinical, biological, and therapeutic aspects. CRC Crit Rev Oncol Hematol 10:131–164CrossRefGoogle Scholar
  61. Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M (1991) t(8;21) Breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci USA 88:10431–10434PubMedCrossRefGoogle Scholar
  62. Miyoshi H, Kozu T, Shimizu K et al. (1993) The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J 12:2715–2721PubMedGoogle Scholar
  63. Nowell PC, Hungerford DA (1960) A minute chromosome in human chronic granulocytic leukemia. Science 132:1497–1497Google Scholar
  64. Nüsslein-Volhard C (1996) The identification of genes controlling development in flies and fishes (Nobel lecture). Angewandte Chemie Int Edn 35:2177–2188Google Scholar
  65. O’Hagan RC, Schreiber-Agus N, Chen K et al. (2000) Genetarget recognition among members of the Myc superfamily and implications for oncogenesis. Nat Genet 24:113–119PubMedCrossRefGoogle Scholar
  66. Okuda T, Van Deursen J, 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 84:321–330PubMedCrossRefGoogle Scholar
  67. Petridou E, Trichopoulos D, Dessypris N et al. (1996) Infant leukaemia after in utero exposure to radiation from Chernobyl. Nature 382:352–353PubMedCrossRefGoogle Scholar
  68. Pieters R, Huismans DR, Loonen AH et al. (1991) Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia. Lancet 338:399–403PubMedCrossRefGoogle Scholar
  69. Pieters R, Den Boer ML, Durian M et al. (1998) Relation between age, immunophenotype and in vitro drug resistance in 395 children with acute lymphoblastic leukemia — implications for treatment of infants. Leukemia 12:1344–1348PubMedCrossRefGoogle Scholar
  70. Pui C-H (1995) Childhood leukemias. N Engl J Med 332:1618–1630PubMedCrossRefGoogle Scholar
  71. Raimondi SC (1993) Current status of cytogenetic research in childhood acute lymphoblastic leukemia. Blood 81:2237–2251PubMedGoogle Scholar
  72. Repp R, Keller C, Borkhardt A et al. (1992) Detection of a hepatitis B virus variant with a truncated X gene and enhancer II. Arch Virol 125:299–304PubMedCrossRefGoogle Scholar
  73. Repp R, Horsten B von, Cseke A et al. (1993) Clinical and immunological aspects of hepatitis B virus infection in children receiving multidrug cancer chemotherapy. Arch Virol [Suppl] 8:103–111Google Scholar
  74. Ribeiro RC, Pui C-H (1993) Prognostic factors in childhood acute lymphoblastic leukemia. Hematol Pathol 7:121–142PubMedGoogle Scholar
  75. Ross JA (2000) Dietary flavonoids and the MLL gene: a pathway to infant leukemia? Proc Natl Acad Sci USA 97:4411–4413PubMedCrossRefGoogle Scholar
  76. Rowley JD (1973) A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290–293PubMedCrossRefGoogle Scholar
  77. Rubnitz JE, Shuster JJ, Land VJ et al. (1997) Case-control study suggests a favorable impact of TEL rearrangement in patients with B-lineage acute lymphoblastic leukemia treated with antimetabolite-based therapy: a pediatric oncology group study. Blood 89:1143–1146PubMedGoogle Scholar
  78. Rubnitz JE, Camitta BM, Mahmoud H et al. (1999) Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19)(q23;p13.3) translocation. J Clin Oncol 17:191–196PubMedGoogle Scholar
  79. Salgia R, Li JL, Ewaniuk DS et al. (1997) BCR/ABL induces multiple abnormalities of cytoskeletal function. J Clin Invest 100:46–57PubMedCrossRefGoogle Scholar
  80. Schlehofer B, Blettner M, Geletneky K et al. (1996) Sero-epidemiological analysis of the risk of virus infections for childhood leukaemia. Int J Cancer 65:584–590PubMedCrossRefGoogle Scholar
  81. Schlieben S, Borkhardt A, Reinisch I et al. (1996) Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05-92. Leukemia 10:957–963PubMedGoogle Scholar
  82. Schrappe M, Arico M, Harbott J et al. (1998) Philadelphia chromosome-positive (Ph+) childhood acute lymphoblastic leukemia: good initial steroid response allows early prediction of a favorable treatment outcome. Blood 92:2730–2741PubMedGoogle Scholar
  83. Seeker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV (1991) Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. Leukemia 5:196–199Google Scholar
  84. Strick R, Strissel PL, Borgers S, Smith SL, Rowley J (2000) Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proc Natl Acad Sci USA 97:4790–4795PubMedCrossRefGoogle Scholar
  85. Taki T, Ida K, Bessho F et al. (1996) Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia. Leukemia 10:1303–1307PubMedGoogle Scholar
  86. Taylor CG, Stasi R, Bastianelli C et al. (1996) Diagnosis and classification of the acute leukemias: recent advances and controversial issues. Hematol Pathol 10:1–38Google Scholar
  87. Uchida H, Downing JR, Miyazaki Y, Frank R, Zhang J, Nimer SD (1999) Three distinct domains in TEL-AML1 are required for transcriptional repression of the IL-3 promoter. Oncogene 18:1015–1022PubMedCrossRefGoogle Scholar
  88. Ulrich O (1932) Blutransfusionen bei Leukosen im Kindesalter. Z Kinderheilkd 53:487–491CrossRefGoogle Scholar
  89. Van Dongen JJ, Seriu T, Panzer-Grümayer ER et al. (1998) Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet 352:1731–1738PubMedCrossRefGoogle Scholar
  90. Vogler LB, Crist WM, Bockman DE, Peari ER, Lawton AR, Cooper MD (1978) Pre-B-cell leukemia. A new phenotype of childhood lymphoblastic leukemia. N Engl J Med 298:872–878PubMedCrossRefGoogle Scholar
  91. Voncken JW, Kaartinen V, Pattengale PK, Germeraad WTV, Groffen J, Heisterkamp N (1995) BCR/ABL P210 and PI90 cause distinct leukemia in transgenic mice. Blood 86:4603–4611PubMedGoogle Scholar
  92. Wang LC, Kuo F, Fujiwara Y, Gilliland DG, Golub TR, Orkin SH (1997) Yolk sac angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets-related factor TEL. EMBO J 16:4374–4383PubMedCrossRefGoogle Scholar
  93. Weisberg E, Griffin JD (2000) Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABL-transformed hematopoietic cell lines. Blood 95:3498–3505PubMedGoogle Scholar
  94. Westbrook CA, Hooberman AL, Spino C et al. (1992) Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: a cancer and leukemia group B study (8762). Blood 80:2983–2990PubMedGoogle Scholar
  95. Wiemels JL, Ford AM, Wering ER van, Postma A, Greaves M (1999 a) Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero. Blood 94:1057–1062PubMedGoogle Scholar
  96. Wiemels JL, Pagnamenta A, Taylor GM et al. (1999b) A lack of a functional NAD(P)H:quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions. Cancer Res 59:4095–4099PubMedGoogle Scholar
  97. Wiersma SR, Ortega J, Sobol E, Weinberg KI (1991) Clinical importance of myeloid-antigen expression in acute lymphoblastic leukemia of childhood. N Engl J Med 325:1378–1382CrossRefGoogle Scholar
  98. Wilimas JA, Marina N, Crist W et al. (1999) Developing a pediatric hematology/oncology parthnership program (PHOPP) in El Salvador. Blood 94 [Suppl 1] 10:367a–367aGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • Arndt Borkhardt

There are no affiliations available

Personalised recommendations