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Phosphorylated CXCR4 is associated with poor survival in adults with B‐acute lymphoblastic leukemia
Author(s) -
Konoplev Sergej,
Jorgensen Jeffrey L.,
Thomas Deborah A.,
Lin E,
Burger Jan,
Kantarjian Hagop M.,
Andreeff Michael,
Medeiros L. Jeffrey,
Konopleva Marina
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26113
Subject(s) - medicine , lymphoblastic leukemia , oncology , leukemia , pediatrics , cancer research
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;. © 2011 American Cancer Society.