The Expression of the SLIT–ROBO Family in Adult Patients with Acute Myeloid Leukemia

Abstract

Introduction: SLIT–ROBO is a ligand–receptor family of neuronal guidance cues that has been involved in pathological and physiological angiogenesis. SLIT–ROBO expression is altered in many tumours. However, no data exist about the role of the whole family in acute myelogenous myeloid leukemia (AML). Purpose: Herein, we assessed the expression of all SLIT–ROBO family in bone marrow (BM) biopsy of AML patients and control group on both protein and RNA levels. Methods: The paraffin-embedded tissue blocks were subjected to immunohistochemistry for SLIT1, SLIT2, SLIT3, ROBO1, ROBO2, ROBO3, and ROBO4. Microvessel density (MVD) was evaluated by CD34 immunohistochemistry. An in silico analysis using The Cancer Genome Atlas data repository was conducted for assessment of RNA level. Results: Acute myeloid leukemia patients were generally high expressers of ROBO1 and ROBO2 compared to the controls (p < 0.0001, p < 0.001, respectively). In contrast, low expression of SLIT1, SLIT2, and SLIT3 ligands has been noted more commonly in AML than in control BM samples (p < 0.0001, p = 0.003, and p = 0.001, respectively). ROBO4 expression correlated with MVD. The in silico analysis showed a poor prognostic value of high ROBO3 and low SLIT2 RNA levels (p = 0.0003 and p = 0.0008, respectively), as well as high ROBO3 and ROBO4 RNA levels in cytogenetic poor risk groups of patients (p = 0.0029 and p = 0.0003, respectively). Conclusions: These data indicate that SLIT–ROBO family members play a role in the biology of AML. Low expression of SLIT in BM of AML patients may suggest its expression alterations in AML. Increased expression of ROBO1 and ROBO2 in AML patients suggests their participation in AML pathogenesis.