الفهرس 
Chronic myeloid leukemiaOnly 14 pages are availabe for public view
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Abstract
CML is a myeloproliferative neoplasm that results from an
acquired genetic change in a pluripotent haemopoietic stem cell. This
altered stem cell proliferates and generates a population of
differentiated cells that gradually displaces normal haemopoiesis and
leads to a greatly expanded total myeloid mass (especially,
predominant proliferation of granulocytic cells). It is associated with a
characteristic chromosomal translocation called the Philadelphia
chromosome (Victor et al., 2011).
BCR-ABL protein is the pathophysiologic cause of chronic
myeloid leukemia due to its action as a tyrosine kinase, targeted
therapies (the first of which was imatinib mesylate) that specifically
inhibit the activity of the BCR-ABL protein have been developed.
These tyrosine kinase inhibitors can induce complete remissions in
CML, confirming the central importance of BCR ABL as the cause
of CML (Hehlmann et al., 2007).
P53 is a tumor suppressor protein which has many mechanisms
of anticancer function, and plays a role in apoptosis, genomic
stability, and inhibition of angiogenesis.(Gilbert and Scott, 2008).
P53 polymorphism inhibits the in vitro and in vivo response to
imatinib without preventing BCR-ABL kinase inhibition. P53 is
selectively activated by imatinib in BCR-ABL-expressing cells as a
result of BCR-ABL kinase inhibition. Concordantly, p53 mutations
are associated with progression to imatinib resistance in some human
CMLs (Wendel et al., 2006).