TY - JOUR
T1 - B-lineage transcription factors and cooperating gene lesions required for leukemia development
AU - Tijchon, E
AU - Havinga, J
AU - van Leeuwen, F N
AU - Scheijen, B
N1 - Funding Information:
We thank RP Kuiper, LT van der Meer and C Murre for critically reading the manuscript. ET, JH and BS are supported by grants from the Dutch childhood oncology foundation KiKa. FNvL is supported by a grant from The Quality of Life Gala foundation.
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
KW - Animals
KW - B-Lymphocytes/pathology
KW - Humans
KW - Leukemia/etiology
KW - Mutation/genetics
KW - Neoplasm Proteins/genetics
KW - Transcription Factors/genetics
UR - http://www.scopus.com/inward/record.url?scp=84875231561&partnerID=8YFLogxK
U2 - 10.1038/leu.2012.293
DO - 10.1038/leu.2012.293
M3 - Review article
C2 - 23047478
SN - 0887-6924
VL - 27
SP - 541
EP - 552
JO - Leukemia
JF - Leukemia
IS - 3
ER -