The key difference between BCR-ABL p190 and p210 is that BCR-ABL p190 is an oncogenic BCR-ABL tyrosine kinase protein that mainly occurs in B-cell acute lymphoblastic leukemia, while BCR-ABL p210 is an oncogenic BCR-ABL tyrosine kinase protein that mainly occurs in chronic myelogenous leukemia.
BCR-ABL1 is a mutation found in human leukemia. It is formed by the combination of two genes known as BCR and ABL1. BCR-ABL1 is also known as the fusion gene. The BCR gene is normally present on chromosome number 22, while the ABL1 gene is normally present on chromosome number 9. BCR-ABL1 mutation occurs when pieces of BCR and ABL1 genes break off and switch their places. In this mutation, a part of the ABL1 gene in chromosome 9 breaks off and attaches to the breakpoint cluster region of the BCR gene in chromosome 22. The fusion gene is known as BCR-ABL1, and the new chromosome 22 is called the Philadelphia chromosome. This fusion gene makes a tyrosine kinase protein, which always leads to cancers like leukemia. Moreover, depending on the translocation breakpoint in the BCR gene, different BCR-ABL protein isoforms, such as BCR-ABL p190 and p210, are made.
CONTENTS
1. Overview and Key Difference
2. What is BCR-ABL p190
3. What is BCR-ABL p210
4. Similarities – BCR-ABL p190 and p210
5. BCR-ABL p190 vs p210 in Tabular Form
6. Summary – BCR-ABL p190 vs p210
What is BCR-ABL p190?
BCR-ABL p190 is an oncogenic BCR-ABL tyrosine kinase protein isoform made from a fusion gene found in Philadelphia chromosome. BCR-ABL fusion gene is expressed in 20-30 % of adult B-cell acute lymphoblastic leukemia (B-ALL). Among that, in about one-quarter of cases, it expresses the BCR-ABL p210 oncogenic tyrosine kinase protein isoform, and in about three-quarters of cases, it expresses the BCR-ABL p190 oncogenic tyrosine kinase protein isoform. Therefore, this means BCR-ABL 190 occurs in the majority of adult B-cell acute lymphoblastic leukemia.
Adult B-cell acute lymphoblastic leukemia (B-ALL) is a type of blood cancer in which the bone marrow makes too many lymphocytes. However, in contrast to chronic myelogenous leukemia, B-ALL is often accompanied by other additional mutagenic events other than BCR-ABL translocation. Therefore, the survival rate of this leukemia is dramatically low due to relapse and kinase inhibitor resistance. Imatinib is the kinase inhibitor used for the treatment of B-ALL. Anyhow, the response of imatinib in B-ALL is low compared to chronic myelogenous leukemia due to the above reason.
What is BCR-ABL p210?
BCR-ABL p210 is an oncogenic BCR-ABL tyrosine kinase protein isoform made from a fusion gene found in Philadelphia chromosome. This oncogenic protein isoform is the sole hallmark of chronic myeloid leukemia. It is comprised of 501 amino acids and is thus 25% longer than p190 isoform.
Chronic myeloid leukemia (CML) is a blood cancer that begins in the blood-forming myeloid cells or stem cells in the bone marrow, which gives rise to abnormally large amounts of immature white blood cells. In CML, BCR-ABL is the sole oncogenic driver of cancer generation, so treatment with imatinib in this leukemia gives a good stable response and durable remissions in most patients.
What are the Similarities Between BCR-ABL p190 and p210?
- BCR-ABL p190 and p210 are two different types of oncogenic tyrosine kinase protein isoforms made depending on the translocation breakpoint in the BCR
- Both oncogenic tyrosine kinase protein isoforms are always on.
- These protein isoforms can result in adult B-cell acute lymphoblastic leukemia (B-ALL).
- Tyrosine kinase inhibitors like imatinib can control their effect.
What is the Difference Between BCR-ABL p190 and p210?
BCR-ABL p190 is an oncogenic BCR-ABL tyrosine kinase protein that mainly occurs in B-cell acute lymphoblastic leukemia, while BCR-ABL p190 is an oncogenic BCR-ABL tyrosine kinase protein that mainly occurs in the chronic myelogenous leukemia. Thus, this is the key difference between BCR-ABL p190 and p210. Furthermore, BCR-ABL p190 is comparatively a shorter oncogenic tyrosine kinase protein isoform. On the other hand, BCR-ABL p210 is comparatively a longer oncogenic tyrosine kinase protein isoform.
The infographic below presents the differences between BCR-ABL p190 and p210 in tabular form for side-by-side comparison.
Summary – BCR-ABL p190 vs p210
Philadelphia chromosome is a specific genetic abnormality in chromosome 22 cells of leukemia patients. In this translocation, the genetic materials between chromosome 9 and chromosome 22 are exchanged with each other and make a fusion gene called BCR-ABL1. However, depending on the translocation breakpoint in the BCR gene, different BCR-ABL protein isoforms are made from this fusion gene. BCR-ABL p190 and p210 are the two different types of oncogenic tyrosine kinase protein isoforms that are made by the BCR-ABL fusion gene. BCR-ABL p190 is a shorter oncogenic BCR-ABL tyrosine kinase protein isoform mainly found in adult B-cell acute lymphoblastic leukemia (B-ALL). BCR-ABL p210 is a longer oncogenic BCR-ABL tyrosine kinase protein isoform mainly found in chronic myelogenous leukemia. So, this summarizes the difference between BCR-ABL p190 and p210.
Reference:
1. Adnan-Awad, Shady, et al. “Characterization of P190-BCR-ABL Chronic Myeloid Leukemia Reveals Specific Signaling Pathways and Therapeutic Targets.” Nature News, 9 Nov. 2020.
2. Li, S, et al. “The P190, P210, and P230 Forms of the BCR/ABL Oncogene Induce a Similar Chronic Myeloid Leukemia-like Syndrome in Mice but Have Different Lymphoid Leukemogenic Activity.” The Journal of Experimental Medicine, 3 May 1999.
Image Courtesy:
1. “Philadelphia Chromosome” By Aryn89 – Own work (CC BY-SA 4.0) via Commons Wikimedia