Clinical and Prognostic Implications of Roundabout 4 (Robo4) in Adult Patients with Acute Myeloid Leukemia

作者：Chen Yin Kai; Hou Hsin An; Tang Jih Luh^*; Jhuang Jie Yang; Lai Yan Jun; Lee Ming Cheng; Kuo Yuan Yeh; Chou Wen Chien; Liu Chieh Yu; Lin Chung Wu; Chuang Shih Sung; Chen Chien Yuan; Tseng Mei Hsuan; Huang Chi Fei; Chiang Ying Chieh; Lee Fen Yu; Liu Ming Chih; Liu Chia Wen; Yao Ming; Huang Shang Yi; Ko Bor Sheng; Hsu Szu Chun; Wu Shang Ju; Tsay Woei; Chen Yao Chang; Tien Hwei Fang

来源：PLos One, 2015, 10(3): e0119831.

DOI：10.1371/journal.pone.0119831

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 disease- 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.

• 出版日期2015-3-20