الفهرس 
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Abstract
The present study recommends:
• Further studies on a larger sample size to confirm the expression of TIM 3/Galectin-9 in AML patients, including full chromosomal and molecular studies.
• Long term follow up of AML patients following chemotherapy, to correlate the studied parameters with AML outcome, overall and leukemia-free survival and to explore the prognostic impact of TIM 3/Galectin-9 in AML patients.
• An extended research on large number of AML patients to confirm the use of TIM 3 as a potential therapeutic target for AML.
SUMMARY AND CONCLUSION
U
nderstanding the immune biology of AML and designing rational approaches to target the immune environment to improve outcomes is an area of intense research in AML.
AML is often a fatal disease owing to the capability of malignant cells to suppress anti-cancer functional activity of natural killer cells and cytotoxic T cells. Recent evidence clearly demonstrated an involvement of TIM-3 - Galectin-9 pathway in the immune escape mechanism.
TIM-3- Galectin-9 autocrine loop is activated in AML cells resulting in a decrease of immune surveillance and promotion of disease progression. Thus both TIM-3 and Galectin-9 present biomarkers for AML diagnostics and potential targets for AML immune-therapy.
Previous studies have investigated the prognostic significance of TIM3/ Galectin-9 in AML, however the results remained controversial. This prompted us to investigate TIM-3/ Galectin-9 expression in patients with AML and explore the impact of its expression on the clinico-laboratory characteristics and prognostic behavior of denovo-AML patients.
This study was conducted on 56 newly diagnosed AML patients according to the WHO classification and were recruited from Ain Shams University Hospitals ASUH. In addition, 20 age and sex matched adult subjects undergoing bone marrow examination were incorporated as a control group.
Focusing on the association between TIM 3/Galectin-9 expression and patient characteristics, the present study showed no significant correlation between TIM 3/Galectin-9 expression and age, gender, TLC, hemoglobin level, platelet count, bone marrow blasts or peripheral blood blasts.
There was no significant association detected between TIM-3% and FAB subtypes, but a lower expression in M0 subtype and a relatively higher TIM-3 expression in M1-M2 subtypes compared to other FAB subtypes were noted. As regards Galectin-9, our study detected a significant association between Galectin-9 serum level and M1-M2 FAB subtypes followed by M4-M5 FAB subtypes.
In addition, our study investigated the association between TIM-3/Galectin-9 expression and extra medullary disease (EMD) in AML patients and showed that there is no significant association between TIM-3/ Galectin-9 expression and EMD (Out of the 56 AML patients, 22 cases (39.3%) presented with EMD, including 3(5.4%) cases with hepatomegaly, 2 (3.6%) cases with splenomegaly, 17(30.4%) cases with HSM and 12(21.4%) cases with LN enlargement).
Levels of TIM 3 and Galectin-9 were significantly higher in AML patients at time of diagnosis compared with those in the control group. When 29 samples of AML patients were monitored at day 28 of induction chemotherapy, It was found that the expression of TIM-3 and Galectin-9 significantly decreased at day 28 compared to that at initial diagnosis (P<0.001).
In order to evaluate the impact of TIM-3/Galectin-9 expression levels on patient response to the induction chemotherapy, AML patients were divided into low and high expressor groups based on their median TIM-3/Galectin-9 expression levels and we found that neither high or low expressor groups (at diagnosis) showed a significant difference in TIM-3/Galectin-9 levels as regards the achievement of CR. On the other hand, at day 28 of chemotherapy, TIM-3 expression was significantly lower in patients who achieved CR (responders).
In conclusion, the results of our study demonstrated that TIM 3/Galectin-9 expression was significantly upregulated in patients with de novo AML and decreased at day 28 of induction chemotherapy compared to that at initial diagnosis, So we suggest that TIM-3/Galectin-9 can act as specific surface molecules expressed in AML LSCs and their expression can distinguish AML LSCs from normal HSCs this indicating that targeting TIM-3/Galectin-9 may be a useful promising therapeutic approach.
Additionally, we found no significant difference between high or low expressor groups of TIM 3/Galectin-9 expression levels at diagnosis and remission status after induction chemotherapy. Therefore, according to our results TIM 3/Galectin-9 expression levels cannot be employed to predict response to therapy in AML.