الفهرس 
Introduction & Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Acute lymphoblastic leukemia (ALL) is a highly aggressive hematological-malignancy resulting from the proliferation and expansion of lymphoid blasts in the blood, bone marrow and other organs. ALL is a common form of leukemia in children below 5 years of age, occurs with a bimodal distribution with an early peak in children 4 – 5 years old followed by a second peak at ~ 50 years of age ,.
A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). MDR is generated by mechanisms such as the increased efflux of a wide range of chemotherapeutics from the cells. A well-established cause of cancer cell MDR is through the increased expression of the ATP binding cassette (ABC) transporter superfamily, which can export a variety of chemotherapeutics out of the cell. In humans, 48 members of ABC transporters have been identified so far, that have been subdivided into seven families (called ABC A–G) according to their structural features. ABC proteins are mainly involved in molecular trafficking processes, such as the transport of vitamins, lipids (i.e., cholesterol, phospholipids, glycolipids, etc.), bile salts, steroids, toxins, drugs, and metabolites, across biological membranes
ABCA2 transports drugs from the cytoplasm into the lysosomal compartment, where they may become degraded and exported from the cell. The aforementioned mechanism may contribute to MDR. It has been reported that ABCA2 may induce resistance to mitoxantrone, estrogen derivatives and estramustine. It is resistant to the aforementioned compounds. ABCA3 is highly expressed in alveolar epithelial type II cells. It is localized to the limiting membrane of lamellar bodies, acidic and lipid rich organelles for production, storage and regulated secretion of pulmonary surfactant .
Recent studies have found that the genetic expression of these genes is high in cases, where they have relapsed after undergoing chemotherapy, predicting the resistance of these genes to the action of certain drugs used in the treatment (because they act as transports through receptors on the surface of the cell inside Or outside
Therefore, the detection of the genetic expression of these genes in newly diagnosed cases will have a role to play in predicting the future of the disease and in discovering new types of drugs that overcome the phenomenon of multiple drug resistance. Give high gene expression to these two genes without going through relapse after undergoing chemotherapy.
This study aimed to investigate the mRNA expression profile of ABCA2, ABCA3 in newly diagnostic children with ALL and healthy children, and study their relationship to predict the prognosis outcome of disease.
This study included 70 cases, 50 newly diagnosed children with acute lymphocytic leukemia (ALL), with age of less than 18 years (from the Oncology Unit - Mansoura Pediatric Hospital and Oncology Center at Mansoura University and 20 healthy children with age and sex compatibility, All cases have not been treated in advance.
All cases included a comprehensive clinical examination, routine laboratory tests such as a comprehensive blood test at the University Hospital of Mansoura, patients undergoing bone marrow testing, and cellular chemistry (to differentiate between lymphatic and melanoma cancers, The gene expression of both genes was measured using quantitative serial polymerase polymerization in all cases in the PCR unit of the University Children’s Hospital in Mansoura.
To determine the genetic expression of the genes in the study, we separated the genetic material by following a protocol and using for quantitative serial polymerase chain reaction from QIAGENE, Applied Biosystem. The study went through the following stages under the highest levels of sterilization, on the genetic material of any proceeding resulting from any bacterial contamination,
1. Separation of the nucleus ribosome messenger from the blood samples of all the cases under study and kept in special refrigerators under the temperature of -25 C
2. Conversion of the ribosome RNA that was separated into complete copies of the dioxide ribosome supplemented by reverse transcription reaction and kept in special refrigerators under temperature -25 C until use.
3. Conduct quantitative real-time chain polymerase reaction on DNA and supplemental DNA levels of ABCA2 and ABCA3 in all studied cases.
We found that
1- The genetic expression of both ABCA2 and ABCA3 genes was high in newly diagnosed patients compared to healthy ones. In contrast, in the healthy group, the gene expression of both genes was minimal.
2- We found that the cases of patients have a significant decrease in the proportion of hemoglobin and platelets compared to healthy, and a significant increase in the number of white blood cells compared to the healthy group.
And when patients followed up for 16 months while receiving chemotherapy and studying the periods in which they survived until the symptoms of the disease completely or occurred to them relapse or death, we found that:
3- The proportion of patients who had the ability to recover is higher in cases where the expression of gene is low (84%), while the proportion of less than (44%) in those who have a high rate of expression of gene ABCA2, and the proportion of patients who have had a relapse was (16%) for patients with low gene expression, and (56%) for those with high gene expression, the death rate in the group with high genetic expression was (32%) and decreased in the small gene expression group To (4)%.
4- In the case of ABCA3, the percentage of patients who had the ability to cure were higher in cases where the gene expression was low (80%), while the rate was lower to (48%) in those who have a high rate of genetic expression, Patients with relapses were directly proportional to increased gene expression (52%), lower to (20%) for patients with low gene expression, and death rate in group with high gene expression was (32)% The percentage in the low gene expression group is little to (4%).