Phosphorylated CXCR4 is associated with poor survival in adults with B-acute lymphoblastic leukemia.

Abstract

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.

• Authors: Sergej Konoplev, Jeffrey L Jorgensen, Deborah A Thomas, E Lin, Jan Burger, Hagop M Kantarjian, Michael Andreeff, L Jeffrey Medeiros, Marina Konopleva
• Journal: Cancer (Cancer) Vol. 117 Issue 20 Pg. 4689-95 (Oct 15 2011) ISSN: 1097-0142 [Electronic] United States
• PMID: 21456010 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 American Cancer Society.

Chemical References

• Antigens, CD
• HLA-DR Antigens
• Receptors, CXCR4

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antigens, CD (blood, immunology)
• Female
• HLA-DR Antigens (blood, immunology)
• Humans
• Immunohistochemistry
• Immunophenotyping
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Philadelphia Chromosome
• Phosphorylation
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (immunology, metabolism, mortality)
• Predictive Value of Tests
• Prognosis
• Proportional Hazards Models
• Receptors, CXCR4 (immunology, metabolism)
• Remission Induction
• Treatment Outcome