Expression and significance of osteopontin and its receptor CD44v6 in acute myeloid leukemia

Background: The bone marrow niches are proposed to be the supportive microenvironment that offers cytoprotection from chemotherapy and confers a survival advantage to leukemic cells that could be responsible for relapses in patients with acute myeloid leukemia (AML). Osteopontin (OPN) and its receptor CD44v6 play a crucial role in leukemia cell homing to the bone marrow. Aim: This study aimed at investigating the pattern of expression and prognostic impact of OPN and CD44v6 in AML patients and their correlation with each other. Patients and methods: The study was carried out on 70 patients with de-novo AML and 20 age-matched and sex-matched controls. Patients were diagnosed and classified according to the French American British classification/WHO (FAB/WHO) criteria by cytomorphology, immunophenotyping, and cytogenetic analysis. Cellular OPN and surface CD44v6 expression by blast cells was assessed by flow cytometry. Results: OPN was overexpressed by AML blasts (8.2–75.8%; median 25%) compared with the controls ( 5%), with 32/70 (45.7%) showing higher levels than the median ( 25%). CD44v6 was detected in 56/70 (80%) patients, with 30/70 (42.9%) showing high expression (≥20%). OPN expression was correlated positively with that of CD44v6, its overexpression being paralleled by an increase in that of CD44v6. Higher levels of OPN and CD44v6 were not related to patients’ clinical or laboratory data, FAB subtype, cytogenetic risk group, and initial response to primary induction chemotherapy. A shorter event-free survival was observed in patients with higher OPN and CD44v6 expression (4 months) compared with those with lower levels (16 months), and elevated OPN and CD44v6 at diagnosis were each identified as a negative independent prognostic marker. Conclusion: OPN and its receptor CD44v6 levels of expression are increased in AML, correlate with each other, and their higher levels at diagnosis can be used as early prognostic markers to predict poor disease progression.