الفهرس 
ACUTE MYELOID LEUKEMIAOnly 14 pages are availabe for public view
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Abstract
Chemokines are a family of proteins that chemoattract and activate cells by interacting with G protein-coupled receptors on the surface of their target cells. They are grouped into four classes based on the position of key cysteine residues: C, CC, CXC and CX3C. The CXCR4 is a chemokine receptor that binds SDF-1.
The AML has the lowest survival rate of all leukemias. So, assessment of the prognostic factors in AML is very important. Recently, CXCR4 expression was described to have a prognostic impact in AML.
The aim of this study was to evaluate the chemokine receptor CXCR4 expression in AML patients, and to correlate this expression with other prognostic factors.
The current study was carried out on 40 newly diagnosed AML patients who were investigated for CXCR4 by FCM. The CXCR4 was expressed in all studied AML patients.
Using the receiver operating characteristic (ROC) curve, cut-off values for CXCR4% and CXCR4-MFI were evaluated and identified in order to allow the most significant separation and differentiation between AML cases with remission or relapse/death. The cut-off value for CXCR4% was 30%, and for CXCR4-MFI was 1.3. The CXCR4% cut-off of 30% had sensitivity of 76.67%, specificity of 80.00% and diagnostic accuracy of 77.50%. The CXCR4-MFI cut-off of 1.3 had sensitivity of 73.33%, specificity of 70.00% and diagnostic accuracy of 72.50%.
According to the chosen cut-off values, the 40 studied AML patients fitted into 2 groups. Fifteen patients (37.5%) had low CXCR4 values (below these cut-off levels) and assigned as “low CXCR4 expression group”. Meanwhile, 25 patients (62.5%) with high CXCR4 values (above these levels) were classified as “high CXCR4 expression group”. Both groups were subjected to statistical comparison.
Although the presence of hepatomegaly, splenomegaly and lymphadenopathy provides an indirect measurement of leukemic cell burden, none of these clinical variables had any significant association or correlation with CXCR4 expression in the present study.
Expression of CXCR4 was heterogenous in different FAB subtypes. The highest CXCR4% expression was observed in M4/5 and M3, followed by M2, while the lowest CXCR4% expression was observed in M0 and M1. This heterogeneity of CXCR4% expression, as regards the FAB subtypes, was found to be significant.
The study showed a significant reduction in PB blasts% and CD117 and a highly significant elevation in CD14 with high CXCR4% group of AML than low expression group. A significant elevation was found in TLC and HLA-DR in AML patients with high CXCR4-MFI than those with low expression.
A significant negative correlation was found between CXCR4% and PB blasts%, CD117% and overall survival and significant positive correlation between CXCR4% and CD14 and CD15. The AML with monocytic differentiation expressed the greatest level of CXCR4 among AML subtypes. As regards the CXCR4-MFI, it showed significant negative correlation with Hb level and CD117.
The CXCR4 expression (both % and MFI) showed significant relation with disease outcome and disease free survival (DFS). The AML patients group with high CXCR4 expression had poorer outcome and shorter DFS than the group with low expression.
A highly significant negative correlation between CXCR4% and OS was found, so elevated expression of CXCR4 has been correlated to shortened overall survival (OS). Although the high CXCR4 (% & MFI) expression group had shorter OS than the low CXCR4 expression group, but, the difference was statistically insignificant.
Multivariate forward stepwise logistic regression analysis was used for the detection of the independent prognostic predictors. The CXCR4% was proved to be the best single independent prognostic factor in predicting disease outcome (72.5%). Adding CXCR4-MFI achieved better prediction of response (82.5%). When PB blasts % was added to CXCR4% of expression and CXCR4-MFI, the best prediction of response was obtained (87.5%). This means that the CXCR4% can be used in predicting the outcome of AML patients, as a single prognosticator, or in combination with CXCR4-MFI and PB blasts %, for risk stratification of AML patients at diagnosis.
Finally, the results of the present study confirmed that CXCR4% is an independent prognostic predictor for AML relapse and survival being associated with shorter OS and DFS. Moreover, CXCR4 expression provided an independent adverse prognostic factor in risk stratification of AML patients. Additionally, the present data indicates that CXCR4 surface expression (% and MFI) is an important prognostic marker in AML which can rapidly and easily be determined at disease presentation. The CXCR4 expression, therefore, should be incorporated into the initial diagnostic work-up and risk-stratified treatment strategies for all newly diagnosed AML patients.