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Molecularly Targeted Therapy for Infant ALL

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Molecularly Targeted Therapy for Childhood Cancer

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Abstract

Rational combinations of molecularly targeted agents with synergistic conventional cytotoxic chemotherapeutic agents or, ultimately, with one another are urgently needed for infants with acute leukemia. Leukemia is the commonest malignancy during infancy, comprises 2.5 to 5% of ALL and 6 to 14% of AML in pediatrics overall, (Gurney et al. 1999; Smith et al. 1999a; Pui et al. 1995; SEER Cancer Statistics Review 1975–2006) and represents a special leukemia subtype characterized by MLL (Mixed Lineage Leukemia) gene translocations. MLL translocations with heterogeneous partner genes, of which there are >60, (Meyer et al. 2009) are the primary molecular aberrations in infant ALL and infant AML alike; approximately 75 to 80% of infant ALL cases and myelomonocytic/monoblastic AML feature MLL translocations (Pui et al. 1995; Rubnitz et al. 1994; Robinson et al. 2009). Within infant ALL cases with MLL translocations, 70 and 13% involve the AF4 (ALL-1 fused gene from chromosome 4) or ENL (Eleven-nineteen leukemia) partner genes, respectively, (Pui et al. 2003) whereas the partner genes in AML are more diverse. In one recent infant ALL treatment study, these more common partner genes were associated with only approximately 30% 5-year event free survival, with a poorer outcome associated with the CD10− immunophenotype and younger age at diagnosis (Hilden et al. 2006).

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Acknowledgment

The work is supported by Leukemia & Lymphoma Society SCOR 7372-07.

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Authors and Affiliations

  1. Division of Oncology, Department of Pediatrics, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Colket Translational Research Building, Room 4006, 3501 Civic Center Blvd, Philadelphia, PA, USA

    Carolyn A. Felix

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  1. Patrick A. Brown
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  2. Carolyn A. Felix
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Correspondence to Carolyn A. Felix .

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Editors and Affiliations

  1. Director, Center for Childhood Cancer, Nationwide Children’s Hospital, The Research Institute, 700 Children’s Drive 332, Columbus, 43205, Ohio, USA

    Peter J. Houghton

  2. Johns Hopkins The Bunting & Blaustein Ca, Medicine Kimmel Comprehensive Cancer Cen, Orleans Street 1650, Baltimore, 21231, Maryland, USA

    Robert J. Arceci

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Brown, P.A., Felix, C.A. (2010). Molecularly Targeted Therapy for Infant ALL. In: Houghton, P., Arceci, R. (eds) Molecularly Targeted Therapy for Childhood Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69062-9_3

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