Acute Myeloid Leukemia (AML) is a cancerous disease that is defined by the
inability to produce functional and mature blood cells, as well as the uncontrolled
proliferation due to failure to undergo apoptosis of abnormal cells. The most common
therapy for Leukemia, chemotherapy, has proven only to be partially efficient since it
does not target the leukemic stem cells (LSCs) that have a high self-renewal and
repopulation capacity and result in remission of the disease. Therefore targeting
LSCs will provide more efficient therapy. One way to achieve this would be to
inhibit their homing capability to the bone marrow. It has recently been shown that
CD44, an adhesive molecule, plays a crucial role in cell trafficking and lodgement of
both normal and leukemic stem cells. More importantly anti-CD44 monoclonal
antibodies, along with its ability to induce differentiation of leukemic blasts, it inhibits
specifically the homing capacity of LSCs to their micro-environmental niches.
However, these molecular mechanisms that underlie the inhibition of homing have yet
to be determined. To address these questions we conducted in vitro adhesion and
blot-rolling assays to analyze the adherence and rolling capacity of these LSCs before
and after treatment with anti-CD44 monoclonal antibody (mAb). Since
glycosyltransferases play a crucial role in post translational carbohydrate decoration
on adhesion molecules, we analyzed the expression (using quantitative PCR) of the
different glycosyltransferases expressed in LSC's before and after CD44 ligation
(mAb treatment). Furthermore, we analyzed differentiation by flow cytometric
analysis of treated and non-treated LSC's. We anticipate that our results will set forth
new insights into targeted therapies for AML.
| Date of Award | Aug 3 2011 |
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| Original language | English (US) |
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| Awarding Institution | - Biological, Environmental Sciences and Engineering
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| Supervisor | Jasmeen Merzaban (Supervisor) |
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