Overexpression of CEBPA resulting from the translocation t(14;19)(q32;q13) of human precursor B acute lymphoblastic leukemia.
Subtle variation in the expression or function of a small group of transcription factors can drive leukemogenesis. The CEBPA protein is known to regulate the balance between cell proliferation and differentiation during early hematopoietic development and myeloid differentiation. In human myeloid leukemia, CEBPA is frequently inactivated by mutation and indirect and posttranslational mechanisms, in keeping with tumor suppressor properties. We report that CEBPA is activated by juxtaposition to the immunoglobulin gene enhancer upon its rearrangement with the immunoglobulin heavy-chain locus in precursor B-cell acute lymphoblastic leukemia harboring t(14;19)(q32;q13). Overexpression of apparently normal CEBPA RNA or protein was observed in 6 patients. These data indicate that CEBPA may exhibit oncogenic as well as tumor suppressor properties in human leukemogenesis.
Chapiro
Elise
E
Assistance Publique-Hôpitaux de Paris (AP-HP) Service d'Hématologie Biologique, Hôpital Pitié-Salpêtrière, Paris, France.
Russell
Lisa
L
Radford-Weiss
Isabelle
I
Bastard
Christian
C
Lessard
Michel
M
Struski
Stephanie
S
Cave
Helene
H
Fert-Ferrer
Sandra
S
Barin
Carole
C
Maarek
Odile
O
Della-Valle
Veronique
V
Strefford
Jonathan C
JC
Berger
Roland
R
Harrison
Christine J
CJ
Bernard
Olivier A
OA
Nguyen-Khac
Florence
F
D000328:Adult; D000368:Aged; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002648:Child; D002883:Chromosomes, Human, Pair 14; D002888:Chromosomes, Human, Pair 19; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics*; D012334:RNA, Neoplasm / Q000032:analysis; D014178:Translocation, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D007143:Immunoglobulin Heavy Chains; D012334:RNA, Neoplasm