Current Problems in Pediatric and Adolescent Health Care
Volume 38, Issue 3 , Pages 78-94 , March 2008

The ABCs of Infant Leukemia

  • Patrick A. Zweidler-McKay, MD, PhD

      Affiliations

    • The Children’s Cancer Hospital at the University of Texas M.D. Anderson Cancer Center, Houston, Texas
    • ,
  • Joanne M. Hilden, MD

      Affiliations

    • Peyton Manning Children’s Hospital at St. Vincent, Indianapolis, Indiana.

References 

  1. Ries L, Melbert D, Krapcho M, Mariotto A, Miller B, Feuer E, et al. In: SEER Cancer Statistics Review, 1975-2004. Vol. 2007:Bethesda (MD): National Cancer Institute; 2007;
  2. Isaacs H. Fetal and neonatal leukemia. J Pediatr Hematol Oncol. 2003;25:348–361
  3. Francis JS, Sybert VP, Benjamin DR. Congenital monocytic leukemia: report of a case with cutaneous involvement, and review of the literature. Pediatr Dermatol. 1989;6:306–311
  4. Biondi A, Cimino G, Pieters R, Pui CH. Biological and therapeutic aspects of infant leukemia. Blood. 2000;96:24–33
  5. Reaman G. Biology and treatment of acute leukemias in infants. In:  Pui C editors. Treatment of Acute Leukemias: New Directions for Clinical Research. Totowa (NJ): Humana Press; 2003;p. 75–83
  6. Reaman G, Zeltzer P, Bleyer WA, Amendola B, Level C, Sather H, et al. Acute lymphoblastic leukemia in infants less than one year of age: a cumulative experience of the Children’s Cancer Study Group. J Clin Oncol. 1985;3:1513–1521
  7. Pui CH, Kane JR, Crist WM. Biology and treatment of infant leukemias. Leukemia. 1995;9:762–769
  8. Dinndorf PA, Reaman GH. Acute lymphoblastic leukemia in infants: evidence for B cell origin of disease by use of monoclonal antibody phenotyping. Blood. 1986;68:975–978
  9. Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, et al. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet. 2007;370:240–250
  10. Basso G, Putti MC, Cantu-Rajnoldi A, Saitta M, Santostasi T, Santoro N, et al. The immunophenotype in infant acute lymphoblastic leukaemia: correlation with clinical outcome (An Italian multicentre study (AIEOP)). Br J Haematol. 1992;81:184–191
  11. Borkhardt A, Wuchter C, Viehmann S, Pils S, Teigler-Schlegel A, Stanulla M, et al. Infant acute lymphoblastic leukemia—combined cytogenetic, immunophenotypical and molecular analysis of 77 cases. Leukemia. 2002;16:1685–1690
  12. Austin GE, Alvarado CS, Austin ED, Hakami N, Zhao WG, Chauvenet A, et al. Prevalence of myeloperoxidase gene expression in infant acute lymphocytic leukemia. Am J Clin Pathol. 1998;110:575–581
  13. Alvarado CS, Austin GE, Borowitz MJ, Shuster JJ, Carroll AJ, Austin ED, et al. Myeloperoxidase gene expression in infant leukemia: a Pediatric Oncology Group Study. Leuk Lymphoma. 1998;29:145–160
  14. Wasserman R, Galili N, Ito Y, Reichard BA, Shane S, Rovera G. Predominance of fetal type DJH joining in young children with B precursor lymphoblastic leukemia as evidence for an in utero transforming event. J Exp Med. 1992;176:1577–1581
  15. Felix CA, Reaman GH, Korsmeyer SJ, Hollis GF, Dinndorf PA, Wright JJ, et al. Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy. Blood. 1987;70:536–541
  16. Jansen MW, Corral L, van der Velden VH, Panzer-Grumayer R, Schrappe M, Schrauder A, et al. Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement. Leukemia. 2007;21:633–641
  17. Pui CH, Ribeiro RC, Campana D, Raimondi SC, Hancock ML, Behm FG, et al. Prognostic factors in the acute lymphoid and myeloid leukemias of infants. Leukemia. 1996;10:952–956
  18. Hilden JM, Dinndorf PA, Meerbaum SO, Sather H, Villaluna D, Heerema NA, et al. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children’s Oncology Group. Blood. 2006;108:441–451
  19. Pui CH, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W, et al. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet. 2002;359:1909–1915
  20. Pui CH, Chessells JM, Camitta B, Baruchel A, Biondi A, Boyett JM, et al. Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements. Leukemia. 2003;17:700–706
  21. Dreyer Z, Dinndorf P, Sather H, Steuber C, Carroll W, Hilden J, et al. Shortened, intensified therapy in infant ALL: a Pediatric Oncology Group study. Toronto, Canada: American Society of Pediatric Hematology/Oncology; 2007;
  22. Pieters R, den Boer ML, Durian M, Janka G, Schmiegelow K, Kaspers GJ, et al. Relation between age, immunophenotype and in vitro drug resistance in 395 children with acute lymphoblastic leukemia—implications for treatment of infants. Leukemia. 1998;12:1344–1348
  23. Tomizawa D, Koh K, Sato T, Kinukawa N, Morimoto A, Isoyama K, et al. Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group. Leukemia. 2007;21(11):2258–2263Epub 2007 Aug 9
  24. Gibson BE, Wheatley K, Hann IM, Stevens RF, Webb D, Hills RK, et al. Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials. Leukemia. 2005;19:2130–2138
  25. Lie SO, Jonmundsson G, Mellander L, Siimes MA, Yssing M, Gustafsson G. A population-based study of 272 children with acute myeloid leukaemia treated on two consecutive protocols with different intensity: best outcome in girls, infants, and children with Down’s syndrome (Nordic Society of Paediatric Haematology and Oncology (NOPHO)). Br J Haematol. 1996;94:82–88
  26. Ross JA, Davies SM, Potter JD, Robison LL. Epidemiology of childhood leukemia, with a focus on infants. Epidemiol Rev. 1994;16:243–272
  27. Webb DK, Harrison G, Stevens RF, Gibson BG, Hann IM, Wheatley K. Relationships between age at diagnosis, clinical features, and outcome of therapy in children treated in the Medical Research Council AML 10 and 12 trials for acute myeloid leukemia. Blood. 2001;98:1714–1720
  28. Ishii E, Okamura J, Tsuchida M, Kobayashi M, Akiyama Y, Nakahata T, et al. Infant leukemia in Japan: clinical and biological analysis of 48 cases. Med Pediatr Oncol. 1991;19:28–32
  29. Vormoor J, Ritter J, Creutzig U, Boos J, Heyen P, Ludwig WD, et al. Acute myelogenous leukaemia in children under 2 years—experiences of the West German AML studies BFM-78, -83 and -87 (AML-BFM Study Group). Br J Cancer Suppl. 1992;18:S63–S67
  30. Felix CA, Lange BJ. Leukemia in infants. Oncologist. 1999;4:225–240
  31. Mundschau G, Gurbuxani S, Gamis AS, Greene ME, Arceci RJ, Crispino JD. Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis. Blood. 2003;101:4298–4300
  32. Homans AC, Verissimo AM, Vlacha V. Transient abnormal myelopoiesis of infancy associated with trisomy 21. Am J Pediatr Hematol Oncol. 1993;15:392–399
  33. Al-Kasim F, Doyle JJ, Massey GV, Weinstein HJ, Zipursky A. Incidence and treatment of potentially lethal diseases in transient leukemia of Down syndrome: Pediatric Oncology Group Study. J Pediatr Hematol Oncol. 2002;24:9–13
  34. Bresters D, Reus AC, Veerman AJ, van Wering ER, van der Does-van den Berg A, Kaspers GJ. Congenital leukaemia: the Dutch experience and review of the literature. Br J Haematol. 2002;117:513–524
  35. Lange B. Infant AML. Am Soc Pediatr Hematol/Oncol. 2007;
  36. Ziemin-van der Poel S, McCabe NR, Gill HJ, Espinosa R, Patel Y, Harden A, 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
  37. Cimino G, Moir DT, Canaani O, Williams K, Crist WM, Katzav S, et al. 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. 1991;51:6712–6714
  38. Djabali M, Selleri L, Parry P, Bower M, Young BD, Evans GA. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat Genet. 1992;2:113–118
  39. Chen CS, Sorensen PH, Domer PH, Reaman GH, Korsmeyer SJ, Heerema NA, 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
  40. Taki T, Ida K, Bessho F, Hanada R, Kikuchi A, Yamamoto K, et al. Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia. Leukemia. 1996;10:1303–1307
  41. Silverman LB, McLean TW, Gelber RD, Donnelly MJ, Gilliland DG, Tarbell NJ, et al. Intensified therapy for infants with acute lymphoblastic leukemia: results from the Dana-Farber Cancer Institute Consortium. Cancer. 1997;80:2285–2295
  42. Martinez-Climent JA, Garcia-Conde J. Chromosomal rearrangements in childhood acute myeloid leukemia and myelodysplastic syndromes. J Pediatr Hematol Oncol. 1999;21:91–102
  43. Pieters R. Biology and treatment of infant leukemias. In:  Pui C editors. Treatment of Acute Leukemias: New Directions for Clinical Research. Totowa (NJ): Humana Press; 2003;p. 61–73
  44. Martinez-Climent JA, Thirman MJ, Espinosa R, Le Beau MM, Rowley JD. Detection of 11q23/MLL rearrangements in infant leukemias with fluorescence in situ hybridization and molecular analysis. Leukemia. 1995;9:1299–1304
  45. Heerema NA, Arthur DC, Sather H, Albo V, Feusner J, Lange BJ, et al. 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. 1994;83:2274–2284
  46. van der Burg M, Beverloo HB, Langerak AW, Wijsman J, van Drunen E, Slater R, et al. Rapid and sensitive detection of all types of MLL gene translocations with a single FISH probe set. Leukemia. 1999;13:2107–2113
  47. Mathew S, Behm F, Dalton J, Raimondi S. Comparison of cytogenetics, Southern blotting, and fluorescence in situ hybridization as methods for detecting MLL gene rearrangements in children with acute leukemia and with 11q23 abnormalities. Leukemia. 1999;13:1713–1720
  48. Hilden JM, Frestedt JL, Moore RO, Heerema NA, Arthur DC, Reaman GH, et al. Molecular analysis of infant acute lymphoblastic leukemia: MLL gene rearrangement and reverse transcriptase-polymerase chain reaction for t(4; 11)(q21; q23). Blood. 1995;86:3876–3882
  49. Barber KE, Ford AM, Harris RL, Harrison CJ, Moorman AV. MLL translocations with concurrent 3′ deletions: interpretation of FISH results. Genes Chromosomes Cancer. 2004;41:266–271
  50. Harrison CJ, Griffiths M, Moorman F, Schnittger S, Cayuela JM, Shurtleff S, et al. A multicenter evaluation of comprehensive analysis of MLL translocations and fusion gene partners in acute leukemia using the MLL FusionChip device. Cancer Genet Cytogenet. 2007;173:17–22
  51. Kowarz E, Burmeister T, Lo Nigro L, Jansen MW, Delabesse E, Klingebiel T, et al. Complex MLL rearrangements in t(4;11) leukemia patients with absent AF4.MLL fusion allele. Leukemia. 2007;21:1232–1238
  52. Heerema NA, Sather HN, Ge J, Arthur DC, Hilden JM, Trigg ME, et al. Cytogenetic studies of infant acute lymphoblastic leukemia: poor prognosis of infants with t(4;11)—a report of the Children’s Cancer Group. Leukemia. 1999;13:679–686
  53. Pui CH, Behm FG, Downing JR, Hancock ML, Shurtleff SA, Ribeiro RC, et al. 11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia. J Clin Oncol. 1994;12:909–915
  54. Moorman AV, Raimondi SC, Pui CH, Baruchel A, Biondi A, Carroll AJ, et al. No prognostic effect of additional chromosomal abnormalities in children with acute lymphoblastic leukemia and 11q23 abnormalities. Leukemia. 2005;19:557–563
  55. Satake N, Maseki N, Nishiyama M, Kobayashi H, Sakurai M, Inaba H, et al. Chromosome abnormalities and MLL rearrangements in acute myeloid leukemia of infants. Leukemia. 1999;13:1013–1017
  56. Pui CH, Raimondi SC, Srivastava DK, Tong X, Behm FG, Razzouk B, et al. Prognostic factors in infants with acute myeloid leukemia. Leukemia. 2000;14:684–687
  57. Lie SO, Abrahamsson J, Clausen N, Forestier E, Hasle H, Hovi L, et al. Treatment stratification based on initial in vivo response in acute myeloid leukaemia in children without Down’s syndrome: results of NOPHO-AML trials. Br J Haematol. 2003;122:217–225
  58. Rubnitz JE, Camitta BM, Mahmoud H, Raimondi SC, Carroll AJ, Borowitz MJ, et al. Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19)(q23;p13.3) translocation. J Clin Oncol. 1999;17:191–196
  59. Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL, Swanton S, et al. Hematologic malignancies with t(4;11)(q21;q23)—a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases (European 11q23 Workshop participants). Leukemia. 1998;12:779–787
  60. Nagayama J, Tomizawa D, Koh K, Nagatoshi Y, Hotta N, Kishimoto T, et al. Infants with acute lymphoblastic leukemia and a germline MLL gene are highly curable with use of chemotherapy alone: results from the Japan Infant Leukemia Study Group. Blood. 2006;107:4663–4665
  61. Sorensen PH, Chen CS, Smith FO, Arthur DC, Domer PH, Bernstein ID, et al. 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. 1994;93:429–437
  62. Ernst P, Wang J, Korsmeyer SJ. The role of MLL in hematopoiesis and leukemia. Curr Opin Hematol. 2002;9:282–287
  63. Fidanza V, Melotti P, Yano T, Nakamura T, Bradley A, Canaani E, et al. Double knockout of the ALL-1 gene blocks hematopoietic differentiation in vitro. Cancer Res. 1996;56:1179–1183
  64. Corral J, Lavenir I, Impey H, Warren AJ, Forster A, Larson TA, et al. An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes. Cell. 1996;85:853–861
  65. Huret JL, Minor SL, Dorkeld F, Dessen P, Bernheim A. Atlas of genetics and cytogenetics in oncology and haematology, an interactive database. Nucleic Acids Res. 2000;28:349–351
  66. Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet. 2002;30:41–47
  67. Brown P, Small D. FLT3 inhibitors: a paradigm for the development of targeted therapeutics for paediatric cancer. Eur J Cancer. 2004;40:707–721discussion 722-4.
  68. Xu F, Taki T, Eguchi M, Kamada N, Ishii E, Endo M, et al. Tandem duplication of the FLT3 gene is infrequent in infant acute leukemia (Japan Infant Leukemia Study Group). Leukemia. 2000;14:945–947
  69. Wang J, Wang T, Li S, Lin L, Gang Y. Flt-3/ITD mutation in pediatric leukemia and its clinical significance. Ai Zheng. 2007;26:58–63
  70. Armstrong SA, Kung AL, Mabon ME, Silverman LB, Stam RW, Den Boer ML, et al. Inhibition of FLT3 in MLL (Validation of a therapeutic target identified by gene expression based classification). Cancer Cell. 2003;3:173–183
  71. Taketani T, Taki T, Sugita K, Furuichi Y, Ishii E, Hanada R, et al. FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant ALL with MLL rearrangements and pediatric ALL with hyperdiploidy. Blood. 2004;103:1085–1088
  72. Armstrong SA, Mabon ME, Silverman LB, Li A, Gribben JG, Fox EA, et al. FLT3 mutations in childhood acute lymphoblastic leukemia. Blood. 2004;103:3544–3546
  73. Stam RW, Schneider P, de Lorenzo P, Valsecchi MG, den Boer ML, Pieters R. Prognostic significance of high-level FLT3 expression in MLL-rearranged infant acute lymphoblastic leukemia. Blood. 2007;110:2774–2775
  74. Stam RW, den Boer ML, Schneider P, Nollau P, Horstmann M, Beverloo HB, et al. Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia. Blood. 2005;106:2484–2490
  75. Brown P, Levis M, Shurtleff S, Campana D, Downing J, Small D. FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression. Blood. 2005;105:812–820
  76. Brown P, Levis M, McIntyre E, Griesemer M, Small D. Combinations of the FLT3 inhibitor CEP-701 and chemotherapy synergistically kill infant and childhood MLL-rearranged ALL cells in a sequence-dependent manner. Leukemia. 2006;20:1368–1376
  77. Rozovskaia T, Feinstein E, Mor O, Foa R, Blechman J, Nakamura T, et al. Upregulation of Meis1 and HoxA9 in acute lymphocytic leukemias with the t(4:11) abnormality. Oncogene. 2001;20:874–878
  78. Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002;1:133–143
  79. Milne TA, Martin ME, Brock HW, Slany RK, Hess JL. Leukemogenic MLL fusion proteins bind across a broad region of the Hox a9 locus, promoting transcription and multiple histone modifications. Cancer Res. 2005;65:11367–11374
  80. Yu BD, Hess JL, Horning SE, Brown GA, Korsmeyer SJ. Altered Hox expression and segmental identity in Mll-mutant mice. Nature. 1995;378:505–508
  81. Roche J, Zeng C, Baron A, Gadgil S, Gemmill RM, Tigaud I, et al. Hox expression in AML identifies a distinct subset of patients with intermediate cytogenetics. Leukemia. 2004;18:1059–1063
  82. Hess JL, Bittner CB, Zeisig DT, Bach C, Fuchs U, Borkhardt A, et al. c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells. Blood. 2006;108:297–304
  83. Sun L, Heerema N, Crotty L, Wu X, Navara C, Vassilev A, et al. Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia. Proc Natl Acad Sci USA. 1999;96:680–685
  84. Yagi T, Hibi S, Takanashi M, Kano G, Tabata Y, Imamura T, et al. High frequency of Ikaros isoform 6 expression in acute myelomonocytic and monocytic leukemias: implications for up-regulation of the antiapoptotic protein Bcl-XL in leukemogenesis. Blood. 2002;99:1350–1355
  85. Ruiz A, Jiang J, Kempski H, Brady HJ. Overexpression of the Ikaros 6 isoform is restricted to t(4;11) acute lymphoblastic leukaemia in children and infants and has a role in B-cell survival. Br J Haematol. 2004;125:31–37
  86. Winandy S, Wu P, Georgopoulos K. A dominant mutation in the Ikaros gene leads to rapid development of leukemia and lymphoma. Cell. 1995;83:289–299
  87. Gurney JG, Ross JA, Wall DA, Bleyer WA, Severson RK, Robison LL. Infant cancer in the U.S.: histology-specific incidence and trends, 1973 to 1992. J Pediatr Hematol Oncol. 1997;19:428–432
  88. Ross JA, Robison LL. MLL rearrangements in infant leukemia: is there a higher frequency in females?. Leuk Res. 1997;21:793–795
  89. Wiemels JL, Pagnamenta A, Taylor GM, Eden OB, Alexander FE, Greaves MF. A lack of a functional NAD(P)H:quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions (United Kingdom Childhood Cancer Study Investigators). Cancer Res. 1999;59:4095–4099
  90. Smith MT, Wang Y, Skibola CF, Slater DJ, Lo Nigro L, Nowell PC, et al. Low NAD(P)H:quinone oxidoreductase activity is associated with increased risk of leukemia with MLL translocations in infants and children. Blood. 2002;100:4590–4593
  91. Eguchi-Ishimae M, Eguchi M, Ishii E, Knight D, Sadakane Y, Isoyama K, et al. The association of a distinctive allele of NAD(P)H:quinone oxidoreductase with pediatric acute lymphoblastic leukemias with MLL fusion genes in Japan. Haematologica. 2005;90:1511–1515
  92. Lanciotti M, Dufour C, Corral L, Di Michele P, Pigullo S, De Rossi G, et al. Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements. Leukemia. 2005;19:214–216
  93. Garte S, Taioli E, Crosti F, Sainati L, Barisone E, Luciani M, et al. Deletion of parental GST genes as a possible susceptibility factor in the etiology of infant leukemia. Leuk Res. 2000;24:971–974
  94. Wiemels JL, Smith RN, Taylor GM, Eden OB, Alexander FE, Greaves MF. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA. 2001;98:4004–4009
  95. Hjalgrim LL, Rostgaard K, Hjalgrim H, Westergaard T, Thomassen H, Forestier E, et al. Birth weight and risk for childhood leukemia in Denmark (Sweden, Norway, and Iceland). J Natl Cancer Inst. 2004;96:1549–1556
  96. Ross JA, Perentesis JP, Robison LL, Davies SM. Big babies and infant leukemia: a role for insulin-like growth factor-1?. Cancer Causes Control. 1996;7:553–559
  97. Tower RL, Spector LG. The epidemiology of childhood leukemia with a focus on birth weight and diet. Crit Rev Clin Lab Sci. 2007;44:203–242
  98. Spector LG, Davies SM, Robison LL, Hilden JM, Roesler M, Ross JA. Birth characteristics, maternal reproductive history, and the risk of infant leukemia: a report from the Children’s Oncology Group. Cancer Epidemiol Biomarkers Prev. 2007;16:128–134
  99. Spector LG, Xie Y, Robison LL, Heerema NA, Hilden JM, Lange B, et al. Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children’s oncology group. Cancer Epidemiol Biomarkers Prev. 2005;14:651–655
  100. Ford AM, Ridge SA, Cabrera ME, Mahmoud H, Steel CM, Chan LC, et al. In utero rearrangements in the trithorax-related oncogene in infant leukaemias. Nature. 1993;363:358–360
  101. Gale KB, Ford AM, Repp R, Borkhardt A, Keller C, Eden OB, et al. Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA. 1997;94:13950–13954
  102. Greaves M. Pre-natal origins of childhood leukemia. Rev Clin Exp Hematol. 2003;7:233–245
  103. Hunger SP, McGavran L, Meltesen L, Parker NB, Kassenbrock CK, Bitter MA. Oncogenesis in utero: fetal death due to acute myelogenous leukaemia with an MLL translocation. Br J Haematol. 1998;103:539–542
  104. Yeazel MW, Buckley JD, Woods WG, Ruccione K, Robison LL. History of maternal fetal loss and increased risk of childhood acute leukemia at an early age (A report from the Children’s Cancer Group). Cancer. 1995;75:1718–1727
  105. Ross JA, Potter JD, Shu XO, Reaman GH, Lampkin B, Robison LL. Evaluating the relationships among maternal reproductive history, birth characteristics, and infant leukemia: a report from the Children’s Cancer Group. Ann Epidemiol. 1997;7:172–179
  106. Wen W, Shu XO, Potter JD, Severson RK, Buckley JD, Reaman GH, et al. Parental medication use and risk of childhood acute lymphoblastic leukemia. Cancer. 2002;95:1786–1794
  107. Pombo-de-Oliveira MS, Koifman S. Infant acute leukemia and maternal exposures during pregnancy. Cancer Epidemiol Biomarkers Prev. 2006;15:2336–2341
  108. Alexander FE, Patheal SL, Biondi A, Brandalise S, Cabrera ME, Chan LC, et al. Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion. Cancer Res. 2001;61:2542–2546
  109. Shu XO, Ross JA, Pendergrass TW, Reaman GH, Lampkin B, Robison LL. Parental alcohol consumption, cigarette smoking, and risk of infant leukemia: a Children’s Cancer Group study. J Natl Cancer Inst. 1996;88:24–31
  110. Menegaux F, Steffen C, Bellec S, Baruchel A, Lescoeur B, Leverger G, et al. Maternal coffee and alcohol consumption during pregnancy, parental smoking and risk of childhood acute leukaemia. Cancer Detect Prev. 2005;29:487–493
  111. Trivers KF, Mertens AC, Ross JA, Steinbuch M, Olshan AF, Robison LL. Parental marijuana use and risk of childhood acute myeloid leukaemia: a report from the Children’s Cancer Group. Paediatr Perinat Epidemiol. 2006;20:110–118(United States and Canada)
  112. Casteleyn L, van Damme K. Pilot study on the influence of maternal and paternal occupational exposure and of other external factors on the incidence of congenital leukemia (European Commission Biomedical and Health Research Programme). Lueven, Belgium: University of Leuven; 1998;
  113. Mangano JJ. Childhood leukaemia in US may have risen due to fallout from Chernobyl. BMJ. 1997;314:1200
  114. Pui CH, Relling MV, Rivera GK, Hancock ML, Raimondi SC, Heslop HE, et al. Epipodophyllotoxin-related acute myeloid leukemia: a study of 35 cases. Leukemia. 1995;9:1990–1996
  115. Felix CA, Hosler MR, Winick NJ, Masterson M, Wilson AE, Lange BJ. ALL-1 gene rearrangements in DNA topoisomerase II inhibitor-related leukemia in children. Blood. 1995;85:3250–3256
  116. Pedersen-Bjergaard J, Andersen MK, Johansson B. Balanced chromosome aberrations in leukemias following chemotherapy with DNA-topoisomerase II inhibitors. J Clin Oncol. 1998;16:1897–1898
  117. Pui CH, Relling MV, Behm FG, Hancock ML, Boyett JM, Raimondi SC, et al. L-asparaginase may potentiate the leukemogenic effect of the epipodophyllotoxins. Leukemia. 1995;9:1680–1684
  118. Aplan PD, Chervinsky DS, Stanulla M, Burhans WC. Site-specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitors. Blood. 1996;87:2649–2658
  119. Libura J, Slater DJ, Felix CA, Richardson C. Therapy-related acute myeloid leukemia-like MLL rearrangements are induced by etoposide in primary human CD34+ cells and remain stable after clonal expansion. Blood. 2005;105:2124–2131
  120. Moneypenny CG, Shao J, Song Y, Gallagher EP. MLL rearrangements are induced by low doses of etoposide in human fetal hematopoietic stem cells. Carcinogenesis. 2006;27:874–881
  121. Ross JA, Potter JD, Robison LL. Infant leukemia, topoisomerase II inhibitors, and the MLL gene. J Natl Cancer Inst. 1994;86:1678–1680
  122. Ross JA. Dietary flavonoids and the MLL gene: a pathway to infant leukemia?. Proc Natl Acad Sci USA. 2000;97:4411–4413
  123. Strick R, Strissel PL, Borgers S, Smith SL, Rowley JD. Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proc Natl Acad Sci USA. 2000;97:4790–4795
  124. van Waalwijk van Doorn-Khosrovani SB, Janssen J, Maas LM, Godschalk RW, Nijhuis JG, van Schooten FJ. Dietary flavonoids induce MLL translocations in primary human CD34+ cells. Carcinogenesis. 2007;28:1703–1709
  125. Yamashita Y, Kawada S, Nakano H. Induction of mammalian topoisomerase II dependent DNA cleavage by nonintercalative flavonoids, genistein and orobol. Biochem Pharmacol. 1990;39:737–744
  126. Borkhardt A, Wilda M, Fuchs U, Gortner L, Reiss I. Congenital leukaemia after heavy abuse of permethrin during pregnancy. Arch Dis Child Fetal Neonatal Ed. 2003;88:F436–F437
  127. Ross JA, Potter JD, Reaman GH, Pendergrass TW, Robison LL. Maternal exposure to potential inhibitors of DNA topoisomerase II and infant leukemia (United States): a report from the Children’s Cancer Group. Cancer Causes Control. 1996;7:581–590
  128. Ross JA. Maternal diet and infant leukemia: a role for DNA topoisomerase II inhibitors?. Int J Cancer Suppl. 1998;11:26–28
  129. Hurwitz CA, Schell MJ, Pui CH, Crist WM, Behm F, Mirro J. Adverse prognostic features in 251 children treated for acute myeloid leukemia. Med Pediatr Oncol. 1993;21:1–7
  130. Creutzig U, Ritter J, Schellong G. Identification of two risk groups in childhood acute myelogenous leukemia after therapy intensification in study AML-BFM-83 as compared with study AML-BFM-78 (AML-BFM Study Group). Blood. 1990;75:1932–1940
  131. Woods WG, Kobrinsky N, Buckley JD, Lee JW, Sanders J, Neudorf S, et al. Timed-sequential induction therapy improves postremission outcome in acute myeloid leukemia: a report from the Children’s Cancer Group. Blood. 1996;87:4979–4989
  132. Pui CH, Kalwinsky DK, Schell MJ, Mason CA, Mirro J, Dahl GV. Acute nonlymphoblastic leukemia in infants: clinical presentation and outcome. J Clin Oncol. 1988;6:1008–1013
  133. Chessells JM, Harrison CJ, Kempski H, Webb DK, Wheatley K, Hann IM, et al. Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukaemia working party. Leukemia. 2002;16:776–784
  134. Ravindranath Y, Chang M, Steuber CP, Becton D, Dahl G, Civin C, et al. Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000. Leukemia. 2005;19:2101–2116
  135. Michel G, Baruchel A, Tabone MD, Nelken B, Leblanc T, Thuret I, et al. Induction chemotherapy followed by allogeneic bone marrow transplantation or aggressive consolidation chemotherapy in childhood acute myeloblastic leukemia (A prospective study from the French Society of Pediatric Hematology and Immunology (SHIP)). Hematol Cell Ther. 1996;38:169–176
  136. Grier HE, Gelber RD, Camitta BM, Delorey MJ, Link MP, Price KN, et al. Prognostic factors in childhood acute myelogenous leukemia. J Clin Oncol. 1987;5:1026–1032
  137. Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, et al. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia (Results of the Medical Research Council’s 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council). Blood. 1997;89:2311–2318
  138. Kawasaki H, Isoyama K, Eguchi M, Hibi S, Kinukawa N, Kosaka Y, et al. Superior outcome of infant acute myeloid leukemia with intensive chemotherapy: results of the Japan Infant Leukemia Study Group. Blood. 2001;98:3589–3594
  139. Palle J, Frost BM, Forestier E, Gustafsson G, Nygren P, Hellebostad M, et al. Cellular drug sensitivity in MLL-rearranged childhood acute leukaemia is correlated to partner genes and cell lineage. Br J Haematol. 2005;129:189–198
  140. Odom LF, Gordon EM. Acute monoblastic leukemia in infancy and early childhood: successful treatment with an epipodophyllotoxin. Blood. 1984;64:875–882
  141. Nishikawa A, Nakamura Y, Nobori U, Aoki T, Higashino H, Matsui T, et al. Acute monocytic leukemia in children (Response to VP-16-213 as a single agent). Cancer. 1987;60:2146–2149
  142. Stam RW, den Boer ML, Meijerink JP, Ebus ME, Peters GJ, Noordhuis P, et al. Differential mRNA expression of Ara-C-metabolizing enzymes explains Ara-C sensitivity in MLL gene-rearranged infant acute lymphoblastic leukemia. Blood. 2003;101:1270–1276
  143. Ludwig WD, Rieder H, Bartram CR, Heinze B, Schwartz S, Gassmann W, et al. Immunophenotypic and genotypic features, clinical characteristics, and treatment outcome of adult pro-B acute lymphoblastic leukemia: results of the German multicenter trials GMALL 03/87 and 04/89. Blood. 1998;92:1898–1909
  144. Chessells JM, Eden OB, Bailey CC, Lilleyman JS, Richards SM. Acute lymphoblastic leukaemia in infancy: experience in MRC UKALL trials (Report from the Medical Research Council Working Party on Childhood Leukaemia). Leukemia. 1994;8:1275–1279
  145. Reaman GH, Sposto R, Sensel MG, Lange BJ, Feusner JH, Heerema NA, et al. Treatment outcome and prognostic factors for infants with acute lymphoblastic leukemia treated on two consecutive trials of the Children’s Cancer Group. J Clin Oncol. 1999;17:445–455
  146. Thompson PA, Murry DJ, Rosner GL, Lunagomez S, Blaney SM, Berg SL, et al. Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2007;59:847–853
  147. McLeod HL, Relling MV, Crom WR, Silverstein K, Groom S, Rodman JH, et al. Disposition of antineoplastic agents in the very young child. Br J Cancer Suppl. 1992;18:S23–S29
  148. Dordelmann M, Reiter A, Borkhardt A, Ludwig WD, Gotz N, Viehmann S, et al. Prednisone response is the strongest predictor of treatment outcome in infant acute lymphoblastic leukemia. Blood. 1999;94:1209–1217
  149. Ishii E, Kawasaki H, Isoyama K, Eguchi-Ishimae M, Eguchi M. Recent advances in the treatment of infant acute myeloid leukemia. Leuk Lymphoma. 2003;44:741–748
  150. Woolfrey AE, Gooley TA, Sievers EL, Milner LA, Andrews RG, Walters M, et al. Bone marrow transplantation for children less than 2 years of age with acute myelogenous leukemia or myelodysplastic syndrome. Blood. 1998;92:3546–3556
  151. Emminger W, Emminger-Schmidmeier W, Haas OA, Urban C, Ambros P, Peters C, et al. Treatment of infant leukemia with busulfan, cyclophosphamide +/− etoposide and bone marrow transplantation. Bone Marrow Transplant. 1992;9:313–318
  152. Michel G, Leverger G, Leblanc T, Nelken B, Baruchel A, Landman-Parker J, et al. Allogeneic bone marrow transplantation vs aggressive post-remission chemotherapy for children with acute myeloid leukemia in first complete remission (A prospective study from the French Society of Pediatric Hematology and Immunology (SHIP)). Bone Marrow Transplant. 1996;17:191–196
  153. Marco F, Bureo E, Ortega JJ, Badell I, Verdaguer A, Martinez A, et al. High survival rate in infant acute leukemia treated with early high-dose chemotherapy and stem-cell support (Groupo Espanol de Trasplante de Medula Osea en Ninos). J Clin Oncol. 2000;18:3256–3261
  154. Dreyer Z, Dinndorf P, Sather H, Hilden J, Devidas M, Heerema N, et al. Hematopoietic stem cell transplant (HSCT) versus intensive chemotherapy in infant acute lymphoblastic leukemia (ALL). J Clin Oncol. 2007;25:9514
  155. Pirich L, Haut P, Morgan E, Marymount M, Kletzel M. Total body irradiation, cyclophosphamide, and etoposide with stem cell transplant as treatment for infants with acute lymphocytic leukemia. Med Pediatr Oncol. 1999;32:1–6
  156. Jacobsohn DA, Hewlett B, Morgan E, Tse W, Duerst RE, Kletzel M. Favorable outcome for infant acute lymphoblastic leukemia after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005;11:999–1005
  157. Sanders JE, Im HJ, Hoffmeister PA, Gooley TA, Woolfrey AE, Carpenter PA, et al. Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia. Blood. 2005;105:3749–3756
  158. Landier W, Bhatia S, Eshelman DA, Forte KJ, Sweeney T, Hester AL, et al. Development of risk-based guidelines for pediatric cancer survivors: the Children’s Oncology Group Long-Term Follow-Up Guidelines from the Children’s Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol. 2004;22:4979–4990
  159. Nathan PC, Patel SK, Dilley K, Goldsby R, Harvey J, Jacobsen C, et al. Guidelines for identification of, advocacy for, and intervention in neurocognitive problems in survivors of childhood cancer: a report from the Children’s Oncology Group. Arch Pediatr Adolesc Med. 2007;161:798–806
  160. Leung W, Hudson M, Zhu Y, Rivera GK, Ribeiro RC, Sandlund JT, et al. Late effects in survivors of infant leukemia. Leukemia. 2000;14:1185–1190
  161. Perkins JL, Kunin-Batson AS, Youngren NM, Ness KK, Ulrich KJ, Hansen MJ, et al. Long-term follow-up of children who underwent hematopoeitic cell transplant (HCT) for AML or ALL at less than 3 years of age. Pediatr Blood Cancer. 2007;49(7):958–963Dec
  162. Mulhern RK, Kovnar E, Langston J, Carter M, Fairclough D, Leigh L, et al. Long-term survivors of leukemia treated in infancy: factors associated with neuropsychologic status. J Clin Oncol. 1992;10:1095–1102
  163. Phipps S, Dunavant M, Srivastava DK, Bowman L, Mulhern RK. Cognitive and academic functioning in survivors of pediatric bone marrow transplantation. J Clin Oncol. 2000;18:1004–1011
  164. Oliansky DM, Rizzo JD, Aplan PD, Arceci RJ, Leone L, Ravindranath Y, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in children: an evidence-based review. Biol Blood Marrow Transplant. 2007;13:1–25
  165. Triplett B, Handgretinger R, Pui CH, Leung W. KIR-incompatible hematopoietic-cell transplantation for poor prognosis infant acute lymphoblastic leukemia. Blood. 2006;107:1238–1239
  166. Carroll WL, Bhojwani D, Min DJ, Raetz E, Relling M, Davies S, et al. Pediatric acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2003;102–131
  167. Luciani M, Rana I, Pansini V, Caniglia M, Coletti V, Maraschini A, et al. Infant leukaemia: clinical, biological and therapeutic advances. Acta Paediatr Suppl. 2006;95:47–51
  168. Biondi A, Rizzari C, Valsecchi MG, De Lorenzo P, Arico M, Basso G, et al. Role of treatment intensification in infants with acute lymphoblastic leukemia: results of two consecutive AIEOP studies. Haematologica. 2006;91:534–537
  169. Niitsu N, Hayashi Y, Sugita K, Honma Y. Sensitization by 5-aza-2′-deoxycytidine of leukaemia cells with MLL abnormalities to induction of differentiation by all-trans retinoic acid and 1alpha,25-dihydroxyvitamin D3. Br J Haematol. 2001;112:315–326
  170. Stam RW, den Boer ML, Passier MM, Janka-Schaub GE, Sallan SE, Armstrong SA, et al. Silencing of the tumor suppressor gene FHIT is highly characteristic for MLL gene rearranged infant acute lymphoblastic leukemia. Leukemia. 2006;20:264–271
  171. Yao Q, Weigel B, Kersey J. Synergism between etoposide and 17-AAG in leukemia cells: critical roles for Hsp90 (FLT3, topoisomerase II, Chk1, and Rad51). Clin Cancer Res. 2007;13:1591–1600
  172. Yokoyama A, Somervaille TC, Smith KS, Rozenblatt-Rosen O, Meyerson M, Cleary ML. The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. Cell. 2005;123:207–218
  173. Nakanishi H, Nakamura T, Canaani E, Croce CM. ALL1 fusion proteins induce deregulation of EphA7 and ERK phosphorylation in human acute leukemias. Proc Natl Acad Sci USA. 2007;104:14442–14447
  174. Wood CM, Goodman PA, Vassilev AO, Uckun FM. CD95 (APO-1/FAS) deficiency in infant acute lymphoblastic leukemia: detection of novel soluble Fas splice variants. Eur J Haematol. 2003;70:156–171
  175. Inukai T, Zhang X, Goto M, Hirose K, Uno K, Akahane K, et al. Resistance of infant leukemia with MLL rearrangement to tumor necrosis factor-related apoptosis-inducing ligand: a possible mechanism for poor sensitivity to antitumor immunity. Leukemia. 2006;20:2119–2129
  176. Arakawa H, Nakamura T, Zhadanov AB, Fidanza V, Yano T, Bullrich F, et al. Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene. Proc Natl Acad Sci USA. 1998;95:4573–4578
  177. Lauer SJ, Camitta BM, Leventhal BG, Mahoney D, Shuster JJ, Kiefer G, et al. Intensive alternating drug pairs after remission induction for treatment of infants with acute lymphoblastic leukemia: A Pediatric Oncology Group Pilot Study. J Pediatr Hematol Oncol. 1998;20:229–233
  178. Moricke A, Zimmermann M, Reiter A, Gadner H, Odenwald E, Harbott J, et al. Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: data from the trials ALL-BFM 86, 90, and 95. Klin Padiatr. 2005;217:310–320
  179. van Wering ER, Kamps WA. Acute leukemia in infants (A unique pattern of acute nonlymphocytic leukemia). Am J Pediatr Hematol Oncol. 1986;8:220–224
  180. Park KU, Lee DS, Lee HS, Kim CJ, Cho HI. Granulocytic sarcoma in MLL-positive infant acute myelogenous leukemia: fluorescence in situ hybridization study of childhood acute myelogenous leukemia for detecting MLL rearrangement. Am J Pathol. 2001;159:2011–2016
  181. Rubnitz JE, Link MP, Shuster JJ, Carroll AJ, Hakami N, Frankel LS, et al. Frequency and prognostic significance of HRX rearrangements in infant acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood. 1994;84:570–573
  182. Ludwig WD, Bartram CR, Harbott J, Koller U, Haas OA, Hansen-Hagge T, et al. Phenotypic and genotypic heterogeneity in infant acute leukemia (I. Acute lymphoblastic leukemia). Leukemia. 1989;3:431–439
  183. Cimino G, Rapanotti MC, Elia L, Biondi A, Fizzotti M, Testi AM, et al. ALL-1 gene rearrangements in acute myeloid leukemia: association with M4-M5 French-American-British classification subtypes and young age. Cancer Res. 1995;55:1625–1628
  184. Koller U, Haas OA, Ludwig WD, Bartram CR, Harbott J, Panzer-Grumayer R, et al. Phenotypic and genotypic heterogeneity in infant acute leukemia (II. Acute nonlymphoblastic leukemia). Leukemia. 1989;3:708–714
  185. Ferster A, Bertrand Y, Benoit Y, Boilletot A, Behar C, Margueritte G, et al. Improved survival for acute lymphoblastic leukaemia in infancy: the experience of EORTC-Childhood Leukaemia Cooperative Group. Br J Haematol. 1994;86:284–290
  186. Frankel LS, Ochs J, Shuster JJ, Dubowy R, Bowman WP, Hockenberry-Eaton M, et al. Therapeutic trial for infant acute lymphoblastic leukemia: the Pediatric Oncology Group experience (POG 8493). J Pediatr Hematol Oncol. 1997;19:35–42
  187. Chessells JM, Harrison CJ, Watson SL, Vora AJ, Richards SM. Treatment of infants with lymphoblastic leukaemia: results of the UK Infant Protocols 1987-1999. Br J Haematol. 2002;117:306–314

PII: S1538-5442(07)00116-2

doi: 10.1016/j.cppeds.2007.12.001

Current Problems in Pediatric and Adolescent Health Care
Volume 38, Issue 3 , Pages 78-94 , March 2008

Article Tools

* Image Usage & Resolution