https://scholars.lib.ntu.edu.tw/handle/123456789/468849
標題: | Clinical and prognostic implications of roundabout 4 (Robo4) in adult patients with acute myeloid leukemia | 作者: | YIN-KAI CHEN HSIN-AN HOU JIH-LUH TANG Jhuang J.-Y. Lai Y.-J. Lee M.-C. Kuo Y.-Y. WEN-CHIEN CHOU Liu C.-Y. CHUNG-WU LIN Chuang S.-S. Chen, Chien-Yuan Tseng M.-H. Huang C.-F. Chiang Y.-C. Lee F.-Y. Liu M.-C. Liu C.-W. MING YAO SHANG-YI HUANG BOR-SHENG KO SZU-CHUN HSU SHANG-JU WU WOEI TSAY YAO-CHANG CHEN HWEI-FANG TIEN |
公開日期: | 2015 | 出版社: | Public Library of Science | 卷: | 10 | 期: | 3 | 起(迄)頁: | e0119831 | 來源出版物: | PLoS ONE | 摘要: | Background Robo4 is involved in hematopoietic stem/progenitor cell homeostasis and essential for tumor angiogenesis. Expression of Robo4 was recently found in solid tumors and leukemia stem cells. However, the clinical implications of Robo4 expression in patients with acute myeloid leukemia (AML) remain unclear. Methods We investigated the clinical and prognostic relevance of mRNA expression of Robo4 in bone marrow (BM) mononuclear cells from 218 adult patients with de novo AML. We also performed immunohistochemical staining to assess the Robo4 protein expression in the BM biopsy specimens from 30 selected AML patients in the cohort. Results Higher Robo4 expression was closely associated with lower white blood cell counts, expression of HLA-DR, CD13, CD34 and CD56 on leukemia cells, t(8;21) and ASXL1 mutation, but negatively correlated with t(15;17) and CEBPA mutation. Compared to patients with lower Robo4 expression, those with higher expression had significantly shorter dis-ease-free survival (DFS) and overall survival (OS). This result was confirmed in an independent validation cohort. Furthermore, multivariate analyses showed that higher Robo4 expression was an independent poor prognostic factor for DFS and OS in total cohort and patients with intermediate-risk cytogenetics, irrespective of age, WBC count, karyotype, and mutation status of NPM1/FLT3-ITD, and CEBPA. Conclusions BM Robo4 expression can serve as a new biomarker to predict clinical outcomes in AML patients and Robo4 may serve as a potential therapeutic target in patients with higher Robo4 expression. ? 2015 Chen et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84925843365&doi=10.1371%2fjournal.pone.0119831&partnerID=40&md5=28b4ef253155d82fa2b07e0e980551bc https://scholars.lib.ntu.edu.tw/handle/123456789/468849 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0119831 | SDG/關鍵字: | CCAAT enhancer binding protein alpha; CD34 antigen; CD56 antigen; HLA DR antigen; membrane protein; messenger RNA; microsomal aminopeptidase; roundabout 4 protein; unclassified drug; cell surface receptor; messenger RNA; ROBO4 protein, human; acute granulocytic leukemia; adolescent; adult; age; aged; Article; bone marrow biopsy; bone marrow derived mononuclear cell; cancer prognosis; cancer survival; controlled study; cytogenetics; disease free survival; female; gene expression; human; human cell; immunohistochemistry; karyotype; leukocyte count; major clinical study; male; mutational analysis; overall survival; protein expression; bone marrow; chromosome aberration; genetics; Kaplan Meier method; Leukemia, Myeloid, Acute; metabolism; middle aged; mortality; mutation; pathology; prognosis; remission; treatment outcome; very elderly; young adult; Adolescent; Adult; Aged; Aged, 80 and over; Bone Marrow; Chromosome Aberrations; Female; Gene Expression; Humans; Kaplan-Meier Estimate; Karyotype; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Prognosis; Receptors, Cell Surface; Remission Induction; RNA, Messenger; Treatment Outcome; Young Adult |
顯示於: | 病理學科所 |
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