Despite major improvements in the understanding and treatment of certain leukemias during the past years, the overall survival of patients with acute myelogenous leukemia (AML) remains poor and new prognostic markers and therapeutic strategies are urgently needed. The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 play key roles in retention of hematopoietic cells in the marrow microenvironment and release into the circulation. Rambouts and colleagues recently reported that CXCR4 expression on AML cells correlates with Flt3 mutations and prognosis (Blood 104: 550-57, July 2004). The aim of our study is to evaluate the prognostic significance of CXCR4 surface expression by AML blasts. Ninty newly diagnosed patients with AML were were divided into three groups based on expression of CXCR4 by AML blasts (CXCR4 score A–C). Group A contains patients with a mean fluorescence intensity ratio (MFIR) for CXCR4 <5 (n=32), group B: MFIR 5–10 (n=26), and group C: MFIR >10 (n=32). MFIR was calculated by divding the mean flourescence intensity for CXCR4 by that for the non-specific isotype control of the respective sample and indicates the level of CXCR4 expression. The characteristics for each group are summarized in Table 1.

Previously, we demonstrated that CXCR4 receptors on AML cells mediate adesion and induce migration beneath marrow stromal cells (Burger JA,et al., Br J Haematol. 122: 579–89, August 2003). Because adhesion to stromal elements can affect survival and induce adhesion-mediated drug resistance, antagonists of the CXCR4/SDF-1 axis may increase the efficacy of current treatments. We conclude that CXCR4 expression at time of diagnosis correlates with leukocytosis, LDH, blast persistence after first therapy, relapse rate, and survival. Therfore, CXCR4 expression in AML may be an important progostic factor for complete remission and survival. As such, CXCR4/SDF-1 interaction may provide the basis for a novel therapeutic approach in AML.

CharacteristicScore A (N=32)Score B (N=26)Score C (N=32)
Median CXCR4 MFIR (range) 2.8 (1.0–4.9) 6.9 (5.1–9.4) 17.2 (10.3–73.4) 
Median Age (range) 62.0 (21–89) 59.5 (18–80) 65.0 (32–93) 
Median WBC (range) 2.3 (1.0–14.0) 10.2 (10.2–17) 30.0 (2.7–240) 
Median PLT (range) 56.0 (8–211) 86.0 (13.6–265) 82.5 (4–218) 
Median LDH (range) 251.5 (140–2637) 368.0 (187–1489) 357.0 (144–2760) 
Unfavorable Cytogenetics 4/28 10/24 7/27 
blast persistence after first therapy N=6, 22.2% N=13, 65% N=14, 73.7% 
Relapse Rate 13.8% 52.4% 40% 
Total Deaths N=7, 21.9% N=13, 50% N=17, 53.1% 
Mean overall survival (months) 12.4±11.9 10.3±9.8 8.3±7.4 
Mean follow-up (months)  12.0±19.7  
Median Overall Survival (months) 9.0 (2–52) 6.5 (0–42) 7.0 (0–25) 
Median follow-up (months)  7.0 (0–52)  
CharacteristicScore A (N=32)Score B (N=26)Score C (N=32)
Median CXCR4 MFIR (range) 2.8 (1.0–4.9) 6.9 (5.1–9.4) 17.2 (10.3–73.4) 
Median Age (range) 62.0 (21–89) 59.5 (18–80) 65.0 (32–93) 
Median WBC (range) 2.3 (1.0–14.0) 10.2 (10.2–17) 30.0 (2.7–240) 
Median PLT (range) 56.0 (8–211) 86.0 (13.6–265) 82.5 (4–218) 
Median LDH (range) 251.5 (140–2637) 368.0 (187–1489) 357.0 (144–2760) 
Unfavorable Cytogenetics 4/28 10/24 7/27 
blast persistence after first therapy N=6, 22.2% N=13, 65% N=14, 73.7% 
Relapse Rate 13.8% 52.4% 40% 
Total Deaths N=7, 21.9% N=13, 50% N=17, 53.1% 
Mean overall survival (months) 12.4±11.9 10.3±9.8 8.3±7.4 
Mean follow-up (months)  12.0±19.7  
Median Overall Survival (months) 9.0 (2–52) 6.5 (0–42) 7.0 (0–25) 
Median follow-up (months)  7.0 (0–52)  
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Table

Topics:
cxcr4 receptors, leukemia, myelocytic, acute, prognostic marker, stromal cell-derived factor 1, adhesions, follow-up, antagonists, chemokines, complete remission, fibrinogen

Author notes

Corresponding author

2005, The American Society of Hematology
2004
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