title: Overexpression of amyloid precursor protein in acute myeloid leukemia enhances extramedullary infiltration by MMP-2.
abstract: It is known that leukemia patients with extramedullary infiltration (EMI) have a worse prognosis than patients without it. Recent data indicate that the amyloid precursor protein (APP) is involved in cell adhesion, motility, and proliferation. The expression of APP and its prognostic significance in acute myeloid leukemia (AML) have not been studied. Our study shows that AML/ETO(+) leukemia patients that overexpress APP easily get EMI and that their long-term survival rate is lower than patients without overexpression of APP. In an in vitro study, we knocked down APP in Kasumi-1 cells using small interfering RNA (siRNA). Transwell data show that siRNA/APP substantially impairs cell migration, but it does not inhibit cell proliferation. Furthermore, by quantitative real-time polymerase chain reaction and Western blot, we found that siRNA/APP decreases MMP-2 expression in vitro. Our study provides a novel clue that APP is involved in the extramedullary infiltration of leukemia by MMP-2.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jiang
authors.forename: Guopan
authors.initials: G
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Fanyi
authors.initials: F
authors.lastname: Meng
authors.forename: Wenli
authors.initials: W
authors.lastname: Ma
mesh_terms: D000328:Adult; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017254:Leukemic Infiltration / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C107844:AML1-ETO fusion protein, human; C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000075142:RUNX1 Translocation Partner 1 Protein; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2