title: Inactivation of SHIP1 in T-cell acute lymphoblastic leukemia due to mutation and extensive alternative splicing.
abstract: To understand the mechanism behind aberrant Akt activation in T-ALL, PIK3CA, PTEN and SHIP1 expression and genotype were assessed. No cell lines or primary ALLs harbored PIK3CA mutations. PTEN was expressed in just one-third of the cell lines, but in two-thirds of the primary ALLs, though in the inactivated (phosphorylated) form. SHIP1 was undetectable in most primary ALL and in the T-ALL cell line Jurkat, which harbored a bi-allelic null mutation and a frame-shift deletion; primary ALL harbored the frame-shift as well as other translationally-inactivating deletions and insertions. The inactivation of SHIP1 could play a central role in the deregulation of Akt pathway and tumorigenesis, perhaps in conjunction with PTEN inactivation.
authors.affiliation: Department of Pediatrics Hematology/Oncology, University of California at San Diego, San Diego, CA 92103-8447, United States.
authors.forename: Tony C T
authors.initials: TC
authors.lastname: Lo
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Barnhill
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Kim
authors.forename: Elizabeth Ann
authors.initials: EA
authors.lastname: Nakae
authors.forename: Alice L
authors.initials: AL
authors.lastname: Yu
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Diccianni
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D002648:Child; D017931:DNA Primers; D020868:Gene Silencing; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D009154:Mutation; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*
chemical_list: D017931:DNA Primers; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases