title: Differential requirements for c-Myc in chronic hematopoietic hyperplasia and acute hematopoietic malignancies in Pten-null mice.
abstract: Myeloproliferative disorders (MPDs), lymphoproliferative disorders (LPDs), acute T-lymphocytic or myeloid leukemia and T-lymphocytic lymphoma were developed in inducible Pten (phosphatase and tensin homolog, deleted on chromosome ten)-knockout mice (Pten(-/-)). The appearance of these multiple diseases in one animal model provides an opportunity to study the pathogenesis of multiple diseases simultaneously. To study whether Myc function is required for the development of these hematopoietic disorders in Pten(-/-) mice, we generated inducible Pten/Myc double-knockout mice (Pten(-/-)/Myc(-/-)). By comparing the hematopoietic phenotypes of these double-knockout mice with those of Pten(-/-) mice, we found that both sets of animals developed MPDs and LPDs. However, none of the compound-mutant mice developed acute leukemia or lymphoma. Interestingly, in contrast to the MPDs that developed in Pten(-/-) mice, which are dominated by granulocytes, megakaryocytes predominate in the MPDs of Pten(-/-)/Myc(-/-) mice. Our study suggests that the deregulation of phosphoinositide 3-kinase/Akt signaling in Pten(-/-) hematopoietic cells protects these cells from apoptotic cell death, resulting in chronic proliferative disorders. However, owing to the differential requirement for Myc in granulocyte as compared to megakaryocyte proliferation, Myc deletion converts Pten(-/-) MPDs from granulocyte- to megakaryocyte-dominated conditions. Myc is absolutely required for the development of acute hematopoietic malignancies.
authors.affiliation: Department of Biology, College of Life and Environment Science, Shanghai Normal University, Shanghai, People's Republic of China. jzhang@lumc.edu
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: P
authors.initials: P
authors.lastname: Breslin
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Wei
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology*; D019337:Hematologic Neoplasms / Q000209:etiology* / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009196:Myeloproliferative Disorders / Q000209:etiology* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C045073:Cre recombinase; D019426:Integrases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse