الفهرس 
EtiologyOnly 14 pages are availabe for public view
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Abstract
AML is considered a complex disease due to the involvement of many intersecting pathways. Although the cytogenetic heterogeneity of AML was recognized more than 30 years ago, the wide molecular heterogeneity of the disease has become increasingly noticed over the past 15 years making a dramatic economic and social burden. This is ultimately associated with increased morbidity and mortality besides decreased quality of life.
The interconnection between the pathophysiology of AML and different pathways and biomarkers has been under research for so long, still, there is a lot to be discovered. In this context, some biomarkers are considered an approach in understanding this connection. Of these different biomarkers, FAK, MR-1, EphA4, Src, and total PKC levels were measured.
To date, the serum concentrations of all these five biomarkers and their association with early diagnosis, prognosis beside their impact on patients’ survival and outcomes are yet to be discovered. Thus, our current study was designed to study the circulating levels of these biomarkers in Egyptian adult de novo AML patients.
Additionally, we sought correlating their levels with each other, and with anthropometric parameters, prognostic factors, and OS.
In order to fulfill our aim, this study was conducted on 90 subjects divided in the following two groups:
group (I): The control group:
The first group (n = 20) included apparently healthy age and gender-matched volunteers (8 males and 12 females).
group (II): AML group:
The second group (n = 70) included de novo adult AML patients (30 males and 40 females).
Results of the current study can be summarized as follows:
1. Significantly higher serum FAK, MR-1, Src, and total PKC levels were found in AML patients as compared to the control group while significantly lower serum EphA4 levels were detected in AML patients as compared to the control group.
2. There was insignificant difference between patients’ age or gender and all biomarkers’ serum levels indicating that the serum levels of each biomarker were not affected neither by patients’ age nor by gender.
3. For diagnosis, ROC curves for serum levels of each biomarker showed a significantly high AUC, sensitivity, and specificity indicating the early diagnostic value of each biomarker.
4. We observed a significant negative correlation between FAK and soluble EphA4 concentrations. Moreover, a strong positive correlation was found regarding the serum level of MR-1 with FAK, Src and total PKC.
5. Serum FAK, MR-1, EphA4, Src, and total PKC levels didn’t show any significant difference at P> 0.05 among the different FAB subtypes of AML. Therefore, further study on a larger scale will be necessary to explain their contribution to the pathogenesis of different subtypes of AML.
6. A significant relation was found between each biomarker and some different individual prognostic markers proposing that they all have prognostic values in AML.
7. Finally, serum FAK, MR-1, Src, and total PKC levels were found to be significantly negatively correlated with OS. On the other hand, EphA4 serum level was significantly positively correlated with OS suggesting how they could affect patients’ outcomes.
In conclusion, our study shed the light on FAK, MR-1, EphA4, Src, and total PKC and the assessment of their concentrations in AML subjects in Egyptian population. Revealing correlation between different pairs of them highlighted some steps in the road to discovery of a pathway linking them together after revealing their importance as promising novel early diagnostic and prognostic biomarkers in AML patients beside their impact on patients’ survival and outcomes.