title: B-lineage transcription factors and cooperating gene lesions required for leukemia development.
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.
authors.affiliation: Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Tijchon
authors.forename: J
authors.initials: J
authors.lastname: Havinga
authors.forename: F N
authors.initials: FN
authors.lastname: van Leeuwen
authors.forename: B
authors.initials: B
authors.lastname: Scheijen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D006801:Humans; D007938:Leukemia / Q000209:etiology* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D014157:Transcription Factors