The prognostic value of CXCR4 in acute myeloid leukemia.
BACKGROUND
CXC chemokine receptor (CXCR4) has been shown to be expressed in a subset of acute myeloid leukemia (AML) patients and is correlated with a poor prognosis. CXCR4 expression appears to be an independent prognostic factor for survival in a heterogeneous group of AML patients. To better assess its significance, we analyzed CXCR4 expression in a group of AML patients.


METHODS
The prognostic value of CXCR4 expression in 53 patients with AML presenting between 2003 and 2008 was analyzed. Formalin-fixed, paraffin-embedded bone marrow biopsy or clot sections were stained using immunohistochemical methods.


RESULTS
CXCR4 was expressed in 26 patients (49.1%). A patient age of less than 60 years (P=0.023), achievement of complete remission after induction therapy (P<0.001), and no CXCR4 expression (P=0.010) were all associated with better progression-free survival (PFS). Among mutations of NPM1, CEBPA, FLT3 ITD, and FLT3 D835 and expression of CXCR4, only CXCR4 expression was associated with PFS (P=0.010; by log-rank test). By multivariate analysis, CXCR4 expression was an independent prognostic factor (P=0.001 for PFS and P=0.001 for overall survival). CXCR4 expression in patients with a normal karyotype was detected in 15 of 22 patients (68.2%, relative ratio 4.46, P=0.035). Expression of CXCR4 in normal-karyotype AML showed inferior PFS (median 2.0 vs. 10.7 mo, P=0.026) and had a trend toward inferior overall survival (median 10.8 vs. 14.0 mo, P=0.058).


CONCLUSIONS
These results suggest that CXCR4 expression is associated with poor prognosis in patients with AML. Specifically, CXCR4 expression is common in normal-karyotype AML and is a marker of more aggressive disease in this population. CXCR4 expression could be incorporated into the risk assessment of patients with AML.
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jeong Yeal
JY
Ahn
Katie
K
Seo
Olga K
OK
Weinberg
Daniel A
DA
Arber
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000090243:Nucleophosmin; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*; D012306:Risk; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; C000716967:NPM1 protein, human; D019718:Receptors, CXCR4; D000090243:Nucleophosmin