الفهرس 
History of Acute Myeloid LeukemiaOnly 14 pages are availabe for public view
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Abstract
AML is a relatively rare cancer. There are approximately 10, 500 new cases each year in the United States, and the incidence rate has remained stable from 1995 through 2005. AML accounts for 1.2% of all cancer deaths in the United States.
Specific cytogenetic abnormalities can be found in many patients with AML; the types of chromosomal abnormalities often have prognostic significance The chromosomal translocations encode abnormal fusion proteins, usually transcription factors whose altered properties may cause the ”differentiation arrest.
A number of risk factors for developing AML have been identified, including: other blood disorders, chemical exposures, ionizing radiation, genetics and pre leukemia blood disorders.
Most signs and symptoms of AML are caused by the replacement of normal blood cells with leukemic cells and lack of normal white blood cell production.
If signs and symptoms and/or the results of the physical exam suggest leukemia, the doctor will need to check samples of cells from the blood and bone marrow to be sure of the diagnosis. Other tissue and cell samples may also be taken in order to help guide treatment.
Treatment of AML consists of: 1- chemotherapy, and divided into two phases: induction and post remission (or consolidation) therapy 2-intrathecal chemotherapy 3- radiotherapy 4- targed therapy.
The human chemokine system currently includes more than 40 chemokines and 18 chemokine receptors. Chemokine receptors are defined by their ability to induce directional migration of cells toward a gradient of a chemotactic cytokine (chemotaxis).
Chemokine receptors are present on many different cell types; Initially, these receptors were identified on leukocytes, where they were found to play an important role in the homing of such cells to sites of inflammation. However, during the past few years, hematopoietic and non hematopoietic cells have been found to express receptors for various chemokines that are constitutively expressed in distinct tissue Microenvironments.
Despite a general sensitivity to chemotherapy, long-term disease-free survival in AML remains low because a majority of patients relapse from (MRD). The marrow is considered the primary site for MRD where adhesion to stromal elements may protect from cytotoxic drugs. Adhesion molecules of (VLA)–4 integrin type on AML cells play a critical role for mediating adhesion to stromal fibronectin.
CXCR4 may facilitate VLA-4 signaling by directing spontaneous migration of AML cells beneath marrow stromal cells .On adhesion to marrow stromal fibronectin, AML cells become resistant to spontaneous or drug-induced apoptosis in vitro.
CXCR4 expression by the AML cells favors the enrichment of a more primitive, noncycling subpopulation of AML cells within the stromal layer. These cells may be less susceptible to cytotoxic treatments, and they may represent a reservoir for (MRD) and/or dormant leukemia progenitors.
Further experiments are needed to experimentally prove this hypothesis. CXCR4 antagonists could mobilize AML cells from the protective stromal microenvironments and make them more susceptible to conventional therapy. The general feasibility and safety of such an approach has been demonstrated by studies in which CXCR4 antagonists were administered to patients or volunteers.
Stroma-mediated AML cell protection from chemotherapy can partially be reversed by CXCR4 antagonists in vitro. As such, a clinical trial with administration of a CXCR4 antagonist in an attempt to mobilize AML cells from their protective environment prior to conventional therapy may be feasible in the near future, even though an increased toxicity to normal hematopoiesis due to simultaneous progenitor cell mobilization is a concern.
Collectively, data indicated that CXCR4 surface expression, as determined by flow cytometry, is an important prognostic marker in AML. CXCR4 expression therefore should be incorporated into the initial diagnostic work-up of AML patients treated within clinical trials. Confirmation of these data in a larger series of patients may lead to the incorporation of this marker into the routine diagnostic work-up and into risk-stratified treatment strategies for patients with AML.