The expression of Slit2 and Robo1 increased during retinoic acid syndrome in acute promyelocytic leukemia and impacted differentiated cell migration

• Published in: Translational oncology Vol. 18; p. 101370
• Main Authors: Yang, Haiyan, Zhou, Shengsheng, Lan, Dong, Bin, Yehong, Bao, Wenguang, Wang, Man, Huang, Fengxiang, Peng, Zhigang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2022; Neoplasia Press; Elsevier
• Subjects: Acute promyelocytic leukemia; Cytokines; Original Research; Retinoic acid syndrome; Roundabout receptors; Slit2 protein; Slit2 protein; Acute promyelocytic leukemia; Retinoic acid syndrome; Cytokines; Roundabout receptors
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2022.101370

•The upregulation of Robo1 and Slit2 was first found in APL patients.•The positive correlation between Robo1/Slit2 and retinoic acid syndrome was first demonstrated.•It was demonstrated for the first time that Slit2 induces the migration of differentiated cells.•Slit2 did not inhibit il8-induced differentiated cell migration.
Retinoic acid syndrome (RAS) is a serious complication developed during the induction therapy of acute promyelocytic leukemia (APL). Cytokines and differentiated cells migration play important roles in the development of RAS. Slit guidance ligand 2 (Slit2) and roundabout 1 (Robo1) involve in cell migration. Our study aimed to investigate the expression of Slit2 and Robo1 in APL and check whether they affected promyelocytes migration. 62 cases of newly diagnosed APL patients were involved and received all-trans retinoic acid (ATRA) and arsenic trioxide as induction therapy. Bone marrow cells (BMCs) were obtained on days 0 and 28, and promyelocytes and plasma were collected from day 1 to day 21. The expression of Robo1 in promyelocytes, and that of Slit2 and cytokines, including IL-8,IL-1β and others, in serum were monitored. 20 healthy individuals donated their cells as control. Of the 62 APL patients, 16 (25.81%) patients developed RAS. The expression of Robo1, Slit2 and IL-8 increased significantly with the development of RAS. In the 16 patients with RAS, levels of Slit2, Robo1 and IL-8 were higher during the development of RAS than before or after the RAS (P < 0.05). RhSlit2-N and rhIL-8 induced cells migration, and the migration induced by IL-8 was not inhibited by rhSlit2-N. Elevated Slit2 and Robo1 levels might be useful markers for the diagnosis and treatment of RAS. The levels of Slit2, Robo1 and IL-8 showed a positive correlation with the severity of RAS. Slit2 and IL-8 promoted the migration of differentiated cells.