title: Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein.
abstract: In pro-B cell acute lymphoblastic leukemia (ALL), expression of the E2A-HLF fusion gene as a result of t(17;19)(q22;p13) is associated with poor prognosis, hypercalcemia, and hemorrhagic complications. We previously reported that the E2A-HLF fusion protein protects interleukin-3 (IL-3)-dependent lymphoid cells from apoptosis caused by cytokine starvation. Here, we report that annexin II, a surface phospholipid-binding protein and one of the proposed causes of the hemorrhagic complications of acute promyelocytic leukemia (APL), is also implicated in t(17;19)+ ALL. Annexin II was expressed at high levels in APL cells and in each of 4 t(17;19)+ leukemia cell lines, and annexin II expression was induced by enforced expression of E2A-HLF in leukemia cells. In IL-3-dependent cells, we found that annexin II expression was regulated by IL-3 mainly by Ras pathways, including Ras/phosphatidylinositol 3-kinase pathways. Moreover, E2A-HLF increased annexin II expression in IL-3-dependent cells in the absence of the cytokine. These findings indicate that E2A-HLF induces annexin II by substituting for cytokines that activate downstream pathways of Ras.
authors.affiliation: Division of Hematology, Department of Pediatrics, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inaba
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsui
authors.forename: Mayuko
authors.initials: M
authors.lastname: Okuya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inukai
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Funabiki
authors.forename: Mikiya
authors.initials: M
authors.lastname: Endo
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Kurosawa
mesh_terms: D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D017306:Annexin A2; D016207:Cytokines; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C076554:E2a-Hlf fusion protein, human; D007377:Interleukin-3; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors