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Chapter 19: Problem 15

How do translocations such as the Philadelphia chromosome contribute to cancer?

Short Answer

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Answer: The Philadelphia chromosome contributes to cancer development by forming an abnormal fusion gene, BCR-ABL, producing a constitutively active tyrosine kinase called BCR-ABL oncoprotein. This oncoprotein continuously stimulates pathways promoting cell growth, leading to uncontrollable cell proliferation, which is associated with chronic myeloid leukemia (CML) and, to a lesser extent, acute lymphoblastic leukemia (ALL).

Step by step solution

01

Understand chromosomal translocations and Philadelphia chromosome

Chromosomal translocations are a type of genetic alteration where a segment of one chromosome is transferred to another chromosome. The Philadelphia chromosome is a specific example of a chromosomal translocation, involving the transfer of a piece of chromosome 9 to chromosome 22. This forms an abnormal, shortened chromosome 22 - which is called the Philadelphia chromosome.
02

Learn about cancer development

Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. This process is driven by the accumulation of genetic mutations that lead to the activation of oncogenes (genes that promote cell growth) and the inactivation of tumor suppressor genes (genes that suppress cell growth).
03

Understand the role of the Philadelphia chromosome in cancer

The Philadelphia chromosome contributes to cancer by activating an oncogene called BCR-ABL. The translocation fuses the BCR gene on chromosome 22 with the ABL gene on chromosome 9. This results in the formation of a chimeric BCR-ABL gene, which is then translated into the BCR-ABL oncoprotein.
04

Detail the BCR-ABL oncoprotein's role in cancer development

The BCR-ABL oncoprotein is a constitutively active tyrosine kinase. This means that it is always active and stimulating pathways that promote cell growth, regardless of any signals from the cellular environment. As a result, cells containing the Philadelphia chromosome can grow uncontrollably, leading to the development of cancer. The BCR-ABL oncoprotein is specifically associated with chronic myeloid leukemia (CML) and less frequently with acute lymphoblastic leukemia (ALL).
05

Explain the treatment options for cancers associated with the Philadelphia chromosome

A targeted therapy has been developed to treat cancers associated with the Philadelphia chromosome, called imatinib. Imatinib is a small molecule that specifically inhibits the BCR-ABL tyrosine kinase, blocking its activity and preventing the uncontrolled cell growth caused by the Philadelphia chromosome. This targeted therapy has significantly improved the prognosis for patients with CML and is also effective in some patients with ALL carrying the Philadelphia chromosome.

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