Lentiviral PU.1 overexpression restores differentiation in myeloid leukemic blasts

Article Article scientifique Article Lentiviral PU.1 overexpression restores differentiation in myeloid leukemic blasts eng 2007 author Durual Stéphane 0000-0002-9772-8406 592156 author Rideau Alexandra 526708 author Ruault-Jungblut S author Cossali Dominique Anouck 74879 author Beris Photis 26494 author Piguet Vincent 84926 author Matthes Thomas 27368 1050-1059 10.1038/sj.leu.2404645 17361223 0887-6924 PU.1, a transcription factor of the ETS family, plays a pivotal role in normal hematopoiesis, and particularly in myeloid differentiation. Altered PU.1 function is possibly implicated in leukemogenesis, as PU.1 gene mutations were identified in some patients with acute myeloid leukemia (AML) and as several oncogenic products (AML1-ETO, promyelocytic leukemia-retinoic acid receptor alpha, FMS-like receptor tyrosine kinase 3 internal tandem duplication) are associated with PU.1 downregulation. To demonstrate directly a role of PU.1 in the blocked differentiation of leukemic blasts, we transduced cells from myeloid cell lines and primary blasts from AML patients with a lentivector encoding PU.1. In NB4 cells we obtained increases in PU.1 mRNA and protein, comparable to increases obtained with all-trans retinoic acid-stimulation. Transduced cells showed increased myelomonocytic surface antigen expression, decreased proliferation rates and increased apoptosis. Similar results were obtained in primary AML blasts from 12 patients. These phenotypic changes are characteristic of restored blast differentiation. PU.1 should therefore constitute an interesting target for therapeutic intervention in AML. Adult Aged Antigens CD13/genetics Apoptosis Blast Crisis/pathology Cell Differentiation Female Genetic Vectors Humans Lentivirus/genetics Leukemia Myeloid/drug therapy/pathology Male Middle Aged Proto-Oncogene Proteins/antagonists & inhibitors/genetics/physiology Trans-Activators/antagonists & inhibitors/genetics/physiology Tretinoin/pharmacology Dewey 616 Dewey 617.6 56 Département de médecine 221 211 Biomatériaux 24Q22 false 586 Analyses cellulaires et moléculaires des hémopathies malignes 929 239 Groupe Susanne Scherrer : Unité des biomatériaux 315 Leukemia 21 5 7b5640d7-b7a5-491c-b867-2b12761fa5ca Article (Published version) Restricted leukemia2007.pdf 404949 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine dentaire / Département de réhabilitation oro-faciale / Division de prothèse fixe et biomatériaux / Biomatériaux

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Lentiviral PU.1 overexpression restores differentiation in myeloid leukemic blasts	Leukemia			2007	498	0

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Cossali, Dominique Anouck