Phosphorylated CXCR4 Is Associated With Poor Survival in Adults With B-Acute Lymphoblastic Leukemia

BACKGROUND: CXC chemokine receptor 4 (CXCR4) is activated by phosphorylation (pCXCR4) and is essential for the migration of hematopoietic precursors to bone marrow. CXCR4 overexpression predicts a poor prognosis in patients with acute myeloid leukemia. Data regarding the prognostic impact of CXCR4 in patients with B-acute lymphoblastic leukemia (B-ALL) are sparse and limited to the pediatric population. METHODS: The authors analyzed CXCR4 and pCXCR4 expression in 54 adults with newly diagnosed B-ALL. CXCR4 was assessed by flow cytometry (FC) and immunohistochemistry (IHC) using an anti-CXCR4 antibody. pCXCR4 expression was assessed using an anti-pCXCR4 antibody. RESULTS: The study group included 30 men and 24 women with a median age of 42 years (range, 17-84 years). Philadelphia chromosome was present in 19 patients. The median follow-up was 16 months (range, 17-84 months). Forty-nine patients had a complete response, and 12 patients relapsed with a median relapse free survival >120 weeks. Fifteen patients (28%) died with a median survival >125 weeks. CXCR4 detected by FC and IHC was highly correlated (P < .001). CXCR4 was not associated with clinical or laboratory findings or survival. In contrast, pCXCR4 was associated with higher leukocyte count (P = .006) and serum bilirubin level (P = .03). In multivariate analysis, pCXCR4 expression (P = .027), high serum creatinine level (P < .01), presence of the Philadelphia chromosome (P = .017), and late clinical response (P < .001) were associated with worse overall survival. CONCLUSIONS: The current results indicated that detection of the activated form of CXCR4, pCXCR4, provides independent prognostic information in adult patients with B-ALL. Cancer 2011;117:4689-95. (C) 2011 American Cancer Society.