B-lineage transcription factors and cooperating gene lesions required for leukemia development

E Tijchon, J Havinga, F N van Leeuwen, B Scheijen

Research output: Contribution to journalReview articlepeer-review

Abstract

Differentiation of hematopoietic stem cells into B lymphocytes requires the concerted action of specific transcription factors, such as RUNX1, IKZF1, E2A, EBF1 and PAX5. As key determinants of normal B-cell development, B-lineage transcription factors are frequently deregulated in hematological malignancies, such as B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and affected by either chromosomal translocations, gene deletions or point mutations. However, genetic aberrations in this developmental pathway are generally insufficient to induce BCP-ALL, and often complemented by genetic defects in cytokine receptors and tyrosine kinases (IL-7Rα, CRLF2, JAK2 and c-ABL1), transcriptional cofactors (TBL1XR1, CBP and BTG1), as well as the regulatory pathways that mediate cell-cycle control (pRB and INK4A/B). Here we provide a detailed overview of the genetic pathways that interact with these B-lineage specification factors, and describe how mutations affecting these master regulators together with cooperating lesions drive leukemia development.

Original languageEnglish
Pages (from-to)541-52
Number of pages12
JournalLeukemia
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 2013
Externally publishedYes

Keywords

  • Animals
  • B-Lymphocytes/pathology
  • Humans
  • Leukemia/etiology
  • Mutation/genetics
  • Neoplasm Proteins/genetics
  • Transcription Factors/genetics

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