Is BCR-ABL a protein kinase?

Abstract. Chronic Myeloid Leukemia (CML) is a clonal disease characterized by the presence of the Philadelphia (Ph+) chromosome and its oncogenic product, BCR-ABL, a constitutively active tyrosine kinase, that is present in >90% of the patients.

What does it mean to be BCR-ABL positive?

A BCR-ABL test is most often used to diagnose or rule out chronic myeloid leukemia (CML) or a specific form of acute lymphoblastic leukemia (ALL) called Ph-positive ALL. Ph-positive means a Philadelphia chromosome was found. The test is not used to diagnose other types of leukemia.

What does BCR-ABL tyrosine kinase do?

BCR-ABL tyrosine kinase activity regulates the expression of multiple genes implicated in the pathogenesis of chronic myeloid leukemia. Cancer Res.

Is BCR-ABL fusion protein a tyrosine kinase?

The BCR-ABL fusion protein encoded by the fusion gene has strong tyrosine kinase activity and is the significant molecular biological basis for the pathogenesis of these diseases. Therefore, it has also become an important molecular target for such leukemia.

Is BCR-ABL a receptor tyrosine kinase?

Bcr-Abl is a constitutively active tyrosine kinase with transforming capacity for hematopoietic cells.

What type of protein is BCR-ABL?

A protein made from pieces of two genes that get joined together. It is found in most patients with chronic myelogenous leukemia (CML), and in some patients with acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML).

How is chronic myeloid leukemia diagnosed?

Most people are diagnosed with CML through a blood test called a complete blood count (CBC) before they have any symptoms. A CBC counts the number of different kinds of cells in the blood. A CBC is often done as part of a regular medical checkup. People with CML have high levels of white blood cells.

What does BCR-ABL bind to?

By blocking the binding of ATP, phosphorylation is prevented and Bcr- Abl expressing cells either have a growth disadvantage or they undergo apoptosis [7].

What inhibits BCR-ABL?

Drugs known as tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the standard treatment for CML. These include: Imatinib (Gleevec) Dasatinib (Sprycel)

Is BCR a kinase?

The BCR protein can also act 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. BCR’s kinase activity is likely involved in regulating signaling within cells, although its exact role is unclear.

How does BCR activate ABL?

ABL tyrosine kinase activity is constitutively activated by the juxtaposi- tion of BCR, thus favoring dimerization or tetramerization and subsequent autophosphorylation.