الفهرس 
GENE STRUCTURE ANDOnly 14 pages are availabe for public view
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Abstract
Haemopoietic cells like any other cells are “programmed” to develop, grow, differentiate, and die in response to a complex system of biochemical signals.
Characterization of the biochemical activities and interactions of gene products has revealed an increasingly detailed picture of normal regulation of cell growth and differentiation, and schematic outline of the cellular events leading to leukemogenesis.
Malignant transformation is usually dependent on the cooperation between multiple genetic changes within a single cell. chromosomal abnormalities involving genes whose products are involved in the regulation of cell proliferation, differentiation and apoptosis frequently underline leukemogenesis and lymphogenesis. chromosomal alteration can cause either activation of proto-oncogenes or more commonly creation of fusion genes, moreover, they can lead to inactivation of tumor suppressor genes and promote malignant transformation.
Detection of chromosomal and genetic abnormalities in leukemia provides a powerful tool for diagnosis and allows risk assessment for individual patients at the time of diagnosis, thus giving the opportunity for a risk adapted management. Some of these abnormalities are known to be independent prognostic factors identifying subgroups of patients with rapid disease progression and short survival. Genetic abnormalities are important for detection of residual disease and early relapse. Moreover, they may also be appropriate targets for tumor specific therapy.
Chronic myelogenous leukemia (CML) is a malignant disease of hematopoietic stem cell, characterized by Philadelphia chromosome (BCR/ABL) and biphasic or triphasic clinical course and most often, with a fatal outcome. The growth advantage of Ph positive cells over normal cells in CML could be referred to altered apoptosis and long survival of CML clone, supporting a mechanistic link between genetic instability and malignant evolution in CML.
Genomic aberrations can now be identified in approximately 80% of CLL patients. These abnormalities are mostly associated with evolving disease and may have implications for understanding of genetic events associated with disease progression. The most prevalent abnormalities are triosomy 12, del 13q and del 11q.
In acute lymphoplastic leukemia (ALL), the most common genomic aberrations include chromosome 17 abnormality, Ph chromosome, t (1,19) and chromosome 11 abnormality.
The commonest abnormalities in acute myeloid leukemia (AML), include t(8;21), 5q deletion &11q23 rearrangement.
During the last two decades major advances in the detection of chromosomal abnormalities in human tumors have occurred with the development of chromosomal banding techniques, yet due to the complexity of chromosomal pattern and the interpretation of chromosomal banding pattern -which requires highly skilled personnel- the investigators sought alternative methods for identifying chromosomal and molecular cytogenetic abnormalities such as Fluorescence in situ hybridization, Comparative genomic hybridization, Northern and Southern blot, Polymerase chain reaction, and Microarray.
In conclusion, the detailed information now available on the genetic and biochemical basis of some hematological malignancies may be important on several aspects of the management of patients, including diagnosis, establishing treatment protocol and strategy, monitoring response to therapy and detection of minimal residual disease.