What is the Difference Between BCR-ABL p190 and p210?

The oncogenic Bcr-Abl tyrosine kinase has two major isoforms: p190 and p210. These isoforms are expressed upon the Philadelphia chromosome translocation and have different subcellular localizations and disease associations. The key differences between BCR-ABL p190 and p210 are:

• Disease Association: p210 is the hallmark of chronic myelogenous leukemia (CML), while p190 occurs in the majority of B-cell acute lymphoblastic leukemia (ALL). p190 is also associated with an increased risk of progression to blast phase, especially of lymphoid phenotype.
• Kinase Activity: p190 has higher tyrosine kinase activity than p210, with p190 and p210 activity both elevated relative to c-Abl. p190 is more efficient than p210 in transformation of Rat-1 fibroblasts, as assessed by colony formation in soft agar.
• Signaling Networks: p190 and p210 Bcr-Abl kinases differ in their signaling networks, with p190 activating specific cancer pathways such as Src signaling and interferon pathways. The differential rewiring of the cellular signaling network could result from different degrees of kinase activation.

Despite these differences, both p190 and p210 Bcr-Abl can stimulate the growth of primary B cells in long-term in vitro cultures, eventually leading to oligoclonal populations of pre-B cells that are independent of stroma. Overall, the distinction between p190 and p210 Bcr-Abl isoforms is crucial for understanding the diverse clinical presentations and outcomes in patients with BCR-ABL-driven leukemias.

Comparative Table: BCR-ABL p190 vs p210

BCR-ABL p190 and p210 are two different isoforms of the oncogenic tyrosine kinase protein BCR-ABL, which are involved in the development of leukemia. The key differences between BCR-ABL p190 and p210 are:

• Length: p190 is shorter than p210 by approximately 25% due to the lack of a DH-PH domain unit. Despite this difference, both isoforms have an identical sequence and domain organization.

• Disease Phenotypes: p210 is the molecular hallmark of chronic myelogenous leukemia (CML), while p190 is mainly found in adult B-cell acute lymphoblastic leukemia (B-ALL).

• Kinase Activity: p190 has been shown to exhibit higher kinase activity and increased autophosphorylation compared to p210.

• Subcellular Localization: There is a hypothesis that p210 may have a different subcellular localization than p190, which could lead to differential protein interactions and signaling pathways.

• Mutation Profile: In a study of adult patients with Philadelphia-positive acute lymphoblastic leukemia, the frequency of T315I and E255K/V mutations was significantly higher in patients with p210.

• Clinical Outcomes: Patients with p210 were found to have a higher white blood cell count, platelet count, relative BCR-ABL1 quantification, and lower bone marrow blasts than those with p190. This may contribute to the inferior prognosis observed in p210-associated disease.

Here is a table summarizing the differences between BCR-ABL p190 and p210:

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