الفهرس 
Introductionيوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
For decades, researchers have been seeking to identify the risk factors that are responsible for resistance to chemotherapy, short survival and poor clinical outcome in AML. Recent studies have shown that several molecular and phenotypic markers are associated with poor prognosis such that deeper understanding of these correlations is needed to cure AML. Different strategies are established based on understanding of AML behaviors. Some researchers study and target the phenotypic markers, others study survival, gender correlation with leukemia, and other groups are interested in molecular pathways. But still the variability in expression of the target molecules and the differences in response from patient to patient represent a major challenge for scientists, and further studies for the detection of the ideal tools against AML clone are needed. Until now there have been many trials with different levels of success in stratification of AML because of the differences in expression of each target from one patient to another. therefore, development of comprehensive studies may be a promising way in understating the prognostic factors for each patient. The present study was designed to detect FLT3-ITD gene mutation in adult patient with CN-AML, and its prognostic significance in those patient with gene mutation and to characterize FLT3-ITD according to age, gender, WBCs count , FAB classification and leukemia- associated immunophenotypic markers identified by flowcytometry in those patients with AML. The total patients were 50 diagnosed as de novo AML representing various FAB subtype. they were 27 males and 23 females with mean age (48.6 years), all patients were subjected to thorough history taking, general and local clinical examination. Routine hematological and biochemical investigations of collected blood samples from each patient were done in Mansoura Oncology center labs. We used bone marrow samples to evaluate the presence of FLT3-ITD gene mutation in CN -AML using conventional PCR and also the levels of some markers consisting of CD1a, CD2, CD4, CD5, CD7, CD10, CD11b, CD11c, CD13, CD14, CD16, CD19, CD20, CD22, CD33, CD34, CD36, CD41, CD58, CD61, CD64, CD99, CD117, , cMPO and HLA- DR using flowcytometry technique. This was performed in department of clinical pathology, Mansoura oncology center, Mansoura university. It was found that the FLT3/ITD was detected in 12 patients (24%) with higher incidence in patients less than 40 years old (58.3%) and in males (58.3.%), M3 and M1 subtype showed higher incidence of FLT-ITD gene mutation (40%,33% respectively) than other FAB subtype. WBCS count more than 100000/cmm3, positive CD2 , positive CD64 and positive CD99 were significant predictors of positive FLT3 among studied cases. Among studied cases, 50% of cases with WBCS count more than 100000 were FLT3 positive versus 15.8% of the cases with WBCs count less than 100000, 100% of cases with positive CD2 and CD99 were FLT3-ITD positive versus, 60% of cases with positive CD64 were FLT3-ITD positive versus. Univariate analysis was entered into multivariate analysis to detect that positive CD64 was significant predictor of FLT3 expression among studied cases with the overall percent predicted was 90%, Cases with positive CD64 have increased risk of FLT3 expression by 10.64 more times than cases with negative CD64. AML patients with FLT3-ITD mutation were associated with the worst prognosis. Eleven AML patient patients with FLT3-ITD died less than 6 months after admission (91.7%). Cases with positive FLT3-ITD was associated with lower median overall survival (0.75 versus 12) and disease-free survival (6.04 versus 21.56) than cases with negative FLT3-ITD with statistically significant association (p<0.001). Conclusions It could be concluded that: FLT3-ITD gene mutation is an important prognostic factor in AML patients. FLT3-ITD gene mutation associated with higher incidence of relapse and mortality. - FLT3-ITD gene mutation associated with lower disease-free survival and overall survival time. FLT3-ITD represent 24% of AML patients, more common in AML patient less than 40 years old and in males more than females. FLT3-ITD associated with high WBCs count >100.000/cmm3. CD58 and CD7 are the most frequently observed lymphoid-associated antigens in AML, their incidence 38%,24% respectively. Co-expression of CD2, CD64, or CD99 with FLT3-ITD mutation was associated with poor survival. Expression of CD64 was significant predictor of FLT3-ITD among studied cases.