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10 - Molecular genetics of acute lymphoblastic leukemia

from Part II - Cell biology and pathobiology

Published online by Cambridge University Press:  01 July 2010

By
Adolfo A. Ferrando ,
Jeffrey E. Rubnitz  and
A. Thomas Look
Edited by
Ching-Hon Pui
Adolfo A. Ferrando
Affiliation:
Assistant Professor of Pathology and Pediatrics Institute for Cancer Genetics, Columbia University, Irving Cancer Research Center, New York, NY, USA
Jeffrey E. Rubnitz
Affiliation:
Associate Member, Department of Hematology/Oncology, Director of Fellowship Program, St. Jude Children's Research Hospital, Memphis, TN, USA
A. Thomas Look
Affiliation:
Professor of Pediatrics, Harvard Medical School, Vice Chair for Research, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Ching-Hon Pui
Affiliation:
St. Jude Children's Research Hospital, Memphis
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Summary

Introduction

Although most cases of acute lymphoblastic leukemia (ALL) do not arise from a recognized predisposing genetic condition, this disease is still considered to have a genetic basis. That is, somatically acquired genetic changes contribute in pivotal ways to the genesis of ALL and have important implications for its diagnosis and treatment. Such acquired lesions, restricted to the leukemic clone, include alterations in both the number (ploidy) and structure of the blast cell chromosomes, the latter consisting of reciprocal translocations, inversions, deletions, gene amplifications, and point mutations. Although many of these abnormalities can be detected by routine cytogenetic analysis, others require molecular assays. Molecular identification of the genetic targets of these alterations has led to the isolation and characterization of numerous oncogenes and tumor suppressors, providing valuable clues to the mechanisms of leukemogenesis. In this chapter, we review the molecular basis of childhood ALL, emphasizing the oncogenes, oncoproteins, and tumor suppressors that appear to be critical components of a limited number of transforming pathways.

Proto-oncogene activation

Standard karyotyping can identify chromosomal translocations, including both recurrent and random rearrangements, in about 50% of cases of childhood ALL. When molecular assays are used with cytogenetic analysis, evidence of a translocation is seen in about 70% of cases (Fig. 10.1). Translocations in ALL most often disrupt genes that encode transcription factors (Tables 10.1 and 10.2), defined as nuclear proteins that bind to DNA and regulate the expression of other cellular proteins.

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Information
Childhood Leukemias , pp. 272 - 297
Publisher: Cambridge University Press
Print publication year: 2006

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  • Molecular genetics of acute lymphoblastic leukemia
    • By Adolfo A. Ferrando, Assistant Professor of Pathology and Pediatrics Institute for Cancer Genetics, Columbia University, Irving Cancer Research Center, New York, NY, USA, Jeffrey E. Rubnitz, Associate Member, Department of Hematology/Oncology, Director of Fellowship Program, St. Jude Children's Research Hospital, Memphis, TN, USA, A. Thomas Look, Professor of Pediatrics, Harvard Medical School, Vice Chair for Research, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.011
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  • Molecular genetics of acute lymphoblastic leukemia
    • By Adolfo A. Ferrando, Assistant Professor of Pathology and Pediatrics Institute for Cancer Genetics, Columbia University, Irving Cancer Research Center, New York, NY, USA, Jeffrey E. Rubnitz, Associate Member, Department of Hematology/Oncology, Director of Fellowship Program, St. Jude Children's Research Hospital, Memphis, TN, USA, A. Thomas Look, Professor of Pediatrics, Harvard Medical School, Vice Chair for Research, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.011
Available formats
×

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To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Molecular genetics of acute lymphoblastic leukemia
    • By Adolfo A. Ferrando, Assistant Professor of Pathology and Pediatrics Institute for Cancer Genetics, Columbia University, Irving Cancer Research Center, New York, NY, USA, Jeffrey E. Rubnitz, Associate Member, Department of Hematology/Oncology, Director of Fellowship Program, St. Jude Children's Research Hospital, Memphis, TN, USA, A. Thomas Look, Professor of Pediatrics, Harvard Medical School, Vice Chair for Research, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.011
Available formats
×