title: 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: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA. skonople@mdanderson.org
authors: Sergej
authors: S
authors: Konoplev
authors: Jeffrey L
authors: JL
authors: Jorgensen
authors: Deborah A
authors: DA
authors: Thomas
authors: E
authors: E
authors: Lin
authors: Jan
authors: J
authors: Burger
authors: Hagop M
authors: HM
authors: Kantarjian
authors: Michael
authors: M
authors: Andreeff
authors: L Jeffrey
authors: LJ
authors: Medeiros
authors: Marina
authors: M
authors: Konopleva
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010677:Philadelphia Chromosome; D010766:Phosphorylation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000378:metabolism / Q000401:mortality*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; D019718:Receptors, CXCR4