Document Details

Document Type : Thesis 
Document Title :
Expression of Adhesion Molecules on Acute Myeloid Leukemia Blasts
التعبير عن العناصر الملتصقه في مرض الليوكيميا الحاد
 
Subject : Faculty of Applied Medical Sciences > Medical Laboratory Technology Department -MLT 
Document Language : Arabic 
Abstract : Acute myeloid leukemia (AML) is a clonal disorder of the blood forming myeloid cells characterized by accumulation of immature blast cells in the bone marrow and peripheral blood. The failure of conventional chemotherapy in AML and treatment related mortalities has directed the attention towards targeted therapies. Targeted therapies against specific molecular abnormalities open alternative treatment options. The role of hematopoietic stem cells niche in normal hematopoiesis and its alterations in hematological neoplasms is being seen with growing interest. Several lines of evidences point towards how the microenvironment of the bone marrow may contribute to or be modified by leukemogenesis. On the same note, the role of adhesion molecules as mediators or regulators of normal and leukemic hematopoiesis is being studied. Adhesive interactions are known to trigger specific signal transduction pathway activation which prevents the apoptosis of both normal and malignant cells. A correlation between expression of certain adhesion molecules and disease outcome has been found for AML and other malignant diseases. In this work, we aimed to characterize the expression of certain adhesion molecules on leukemic blasts from 29 primary AML patients. In addition, we used high purity cell sorting to isolate leukemic blasts based on combination of some of these adhesion molecules and known stem cell markers and studied their in vitro functional properties. Our results demonstrate that markers such as CD34, CD105 and CD90 are significantly upregulated in AML blasts as compared to normal peripheral blood. Whereas, CD96 and CD309 are significantly downregulated in AML blasts as compared to normal peripheral blood. For comparing markers relevant for active AML, we compared AML samples with more than 20% blasts to AML samples with less than 20% blasts. Aldehyde dehydrogenase (ALDH), CD34 and CD105 were found to be significantly upregulated in AML samples with more than 20% blasts, indicating the importance of these markers in active AML. When cells from 2 AML patients were sorted on the basis of ALDH and CD34 expression, only cells that were ALDH+ CD34+ gave rise to leukemic colonies, whereas ALDH- cells did not give rise to leukemic colonies. In another patient sample, cells that had CD34+ CD133+ phenotype showed maximum number of leukemic colonies whereas cells expressing CD34+ CD133- phenotype showed few leukemic colonies. Cells that were CD34- CD133- phenotype did not show any leukemic colonies. In conclusion, our results highlight markers such as CD105 and ALDH in combination with CD34 as important marker in AML. Targeting strategies against some of these markers may prove to be useful in eliminating selectively the potential leukemic stem cells. 
Supervisor : Prof. Dr. Mamdooh Abdullah Gari 
Thesis Type : Master Thesis 
Publishing Year : 1437 AH
2016 AD 
Co-Supervisor : Dr. Farid Ahmed 
Added Date : Wednesday, June 22, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
سعد حسن البحيريAlbohairi, Saad HasanResearcherMaster 

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