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Normal Function
The ABL1 gene provides instructions for making a protein involved in many processes in cells throughout the body. The ABL1 protein functions as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. The ABL1 kinase is normally turned off (inactive) and must be turned on (activated) to perform its functions.
The ABL1 kinase can be turned on by a number of different triggers and can add a phosphate group to many different proteins (also called substrates). This diversity allows ABL1 to be involved in a wide variety of cellular processes, including cell growth and division (proliferation), maturation (differentiation), and movement (migration). It can either aid in cell survival or trigger controlled cell death (apoptosis), depending on cellular conditions. The ABL1 kinase interacts with several proteins involved in the network of fibers called the actin cytoskeleton, which makes up the structural framework inside cells. These interactions help control cell migration and the attachment of cells to one another (adhesion), among many other processes. ABL1 can also help regulate the activity of other genes.
The ABL1 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous.
Health Conditions Related to Genetic Changes
Chronic myeloid leukemia
A genetic rearrangement (translocation) involving the ABL1 gene causes a type of cancer of blood-forming cells called chronic myeloid leukemia. This slow-growing cancer leads to an overproduction of abnormal white blood cells. Common features of the condition include excessive tiredness (fatigue), fever, weight loss, and an enlarged spleen.
The translocation involved in this condition, written as t(9;22), fuses part of the ABL1 gene from chromosome 9 with part of the BCR gene from chromosome 22, creating an abnormal fusion gene called BCR-ABL1. The abnormal chromosome 22, containing a piece of chromosome 9 and the BCR-ABL1 fusion gene, is commonly called the Philadelphia chromosome. The translocation is acquired during a person's lifetime and is present only in the abnormal blood cells. This type of genetic change, called a somatic mutation, is not inherited.
The protein produced from the abnormal fusion gene, called BCR-ABL1, functions as a kinase. However, unlike the ABL1 kinase, it does not require signals in the cell to turn it on. The constantly active BCR-ABL1 protein signals cells to continue dividing abnormally and prevents them from self-destructing, which leads to overproduction of the abnormal cells.
The presence of the Philadelphia chromosome provides a target for molecular therapies.
More About This Health ConditionOther cancers
The BCR-ABL1 fusion gene (described above) is also involved in fast-growing blood cell cancers called acute leukemias. It has been found in 5 percent of children and up to 30 percent of adults with B-cell acute lymphoblastic leukemia and very rarely in acute myeloid leukemia. As in chronic myeloid leukemia, the BCR-ABL1 protein stimulates overproduction of abnormal white blood cells, leading to cancer. It is likely that the form of blood cancer that develops is influenced by the type of blood cell that acquires the mutation and other genetic changes that occur.
Rarely, translocations that lead to fusion of the ABL1 gene with genes other than BCR are associated with acute leukemias. For example, the ETV6-ABL1 fusion gene has been found in a small number of cases of B-cell acute lymphoid leukemia, and a chronic leukemia that can resemble chronic myeloid leukemia. The exact mechanisms by which these rare fusion genes lead to blood cancer are not completely understood, although it is likely that the proteins produced from them promote uncontrolled growth of cells.
Other Names for This Gene
- Abelson tyrosine-protein kinase 1
- ABL
- bcr/abl
- bcr/c-abl oncogene protein
- c-ABL
- c-abl oncogene 1, receptor tyrosine kinase
- c-ABL1
- JTK7
- p150
- proto-oncogene c-Abl
- proto-oncogene tyrosine-protein kinase ABL1
- tyrosine-protein kinase ABL1 isoform a
- tyrosine-protein kinase ABL1 isoform b
- v-abl
- v-abl Abelson murine leukemia viral oncogene homolog 1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Chereda B, Melo JV. Natural course and biology of CML. Ann Hematol. 2015 Apr;94 Suppl 2:S107-21. doi: 10.1007/s00277-015-2325-z. Epub 2015 Mar 27. Citation on PubMed
- Colicelli J. ABL tyrosine kinases: evolution of function, regulation, and specificity. Sci Signal. 2010 Sep 14;3(139):re6. doi: 10.1126/scisignal.3139re6. Erratum In: Sci Signal. 2011 Aug 30;4(188):er4. Citation on PubMed or Free article on PubMed Central
- De Braekeleer E, Douet-Guilbert N, Rowe D, Bown N, Morel F, Berthou C, Ferec C, De Braekeleer M. ABL1 fusion genes in hematological malignancies: a review. Eur J Haematol. 2011 May;86(5):361-71. doi: 10.1111/j.1600-0609.2011.01586.x. Epub 2011 Mar 23. Citation on PubMed
- Laneuville P. Abl tyrosine protein kinase. Semin Immunol. 1995 Aug;7(4):255-66. doi: 10.1006/smim.1995.0030. Citation on PubMed
- Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science. 1990 Mar 2;247(4946):1079-82. doi: 10.1126/science.2408149. Citation on PubMed
- Wang JY. The capable ABL: what is its biological function? Mol Cell Biol. 2014 Apr;34(7):1188-97. doi: 10.1128/MCB.01454-13. Epub 2014 Jan 13. Citation on PubMed or Free article on PubMed Central
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.