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CancerQuest > Introduction to Patient Information > Introduction to Cancer by Type > Leukemia: Introduction > Leukemia: Tumor Biology

Leukemia: Tumor Biology

Genetic changes that occur in cancer include mutation of key regulatory genes, changes in protein products, and changes in the amount of product produced by genes (gene expression). As changes accumulate, cells become more abnormal and cancer progresses. Details of genetic change associated with cancer can be found in the Mutation section.

Advances in leukemia research within recent decades have increased our knowledge about the changes that occur in the disease. A large variety of alterations, including point mutations, amplifications, insertions, deletions, and trisomies are important in development of leukemia. Over 300 chromosomal translocations have been identified so far! Understanding the changes that occur and their effects on cell function allows doctors to classify leukemia into subsets with distinct prognoses and treatment strategies.⁽¹⁾

The example of a common translocation, known as the Philadelphia Chromosome, is discussed below. Learn more about translocations

The Philadelphia Chromosome

Translocations involve chromosome breakage and exchange of chromosome fragments. One such translocation, found in over 95% of chronic myeloid leukemias (CML) as well as some acute lymphoblastic leukemias (ALL), occurs between chromosomes 9 and 22. Part of the proto-oncogene abl is removed from chromosome 9 and joined to the bcr gene on chromosome 22. Similarly, part of chromosome 22 is removed and relocated to chromosome 9.⁽²⁾ The exchange leads to the creation of a shortened form of chromosome 22, called the Philadelphia chromosome (after the location of its discovery).

The normal ABL protein functions as a tyrosine kinase. Tyrosine kinases are enzymes that transfer phosphate groups from ATP to other molecules. Activation of key regulatory enzymes in this manner leads to a cascade of events that ultimately results in cell division. The newly created bcr-abl fusion gene located on the Philadelphia chromosome codes for a protein that has increased tyrosine kinase activity, and therefore leads to increased stimulation of cell division, compared to the normal ABL protein. ⁽³⁾

Imatinib (Gleevec®) is a drug that was designed to bind to the BCR-ABL fusion protein. The presence of the drug blocks the binding of ATP, preventing the protein from functioning as a tyrosine kinase. ⁽⁴⁾ Imatinib (Gleevec®) is the gold standard treatment for chronic myeloid leukemia (CML).⁽¹⁾

References for this page:

1. Zhou GB, Li G, Chen SJ, Chen Z. "From dissection of disease pathogenesis to elucidation of mechanisms of targeted therapies: leukemia research in the genomic era." Acta Pharmacol Sin. 2007 Sep;28(9):1434-49. [PUBMED]
2. Hoffbrand AV, Moss PAH, Pettit JE (ed). "Essential Haematology" 5th Edition. Blackwell Publishing, Oxford: 2006. Pg. 180.
3. Hoffbrand AV, Moss PAH, Pettit JE (ed). "Essential Haematology" 5th Edition. Blackwell Publishing, Oxford: 2006. Pg. 174.
4. Hoffbrand AV, Moss PAH, Pettit JE (ed). "Essential Haematology" 5th Edition. Blackwell Publishing, Oxford: 2006. Pg. 155.