Suppression of E-protein activity interferes with the development of BCR-ABL-mediated myeloproliferative disease.
E-proteins are a class of helix-loop-helix (HLH) proteins, which play multiple roles throughout lymphoid development. The DNA binding activities of the E-proteins are regulated by a distinct class of antagonistic HLH proteins, named Id1-4. Here we demonstrate that Id2 deficient mice in a C57BL/6 genetic background exhibit increased cellularity in the granulocyte/myeloid progenitor compartment and show significantly higher numbers of maturing neutrophils. Within 6 months of age, Id2 deficient mice succumbed from overwhelming granulocytosis. The disease closely mimicked the distinctive features of human chronic myeloid leukemia: leukocytosis with maturing neutrophils, splenomegaly, hepatomegaly, and myeloid infiltration into peripheral tissues, including spleen, liver, and lungs. Strikingly, forced Id2 expression in murine bone marrow cells substantially delayed the onset of myeloproliferative disease (MPD). Collectively, these studies show that suppression of E-protein activity interferes with the development of BCR-ABL-mediated MPD.
Ko
Jinkyung
J
Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093, USA.
Patel
Nihal
N
Ikawa
Tomokatsu
T
Kawamoto
Hiroshi
H
Frank
Oliver
O
Rivera
Richard R
RR
Van Etten
Richard A
RA
Murre
Cornelis
C
D016475:3T3 Cells; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D051797:Inhibitor of Differentiation Protein 2 / Q000172:deficiency* / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009196:Myeloproliferative Disorders / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology
C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D016044:Fusion Proteins, bcr-abl