ABL1
Primary Author(s)*
Brian Davis, PhD
Synonyms
ABL proto-oncogene 1 non-receptor tyrosine kinase, Abelson tyrosine-protein kinase 1, ABL, JTK7, p150, c-ABL, v-abl, CHDSKM, c-ABL1; bcr/abl
Genomic Location
Cytoband: 9q34.12
Genomic Coordinates:
chr9:130,713,881-130,887,675(GRCh38/hg38)
chr9:133,589,268-133,763,062(GRCh37/hg19)
Cancer Category/Type
Chronic Myeloid Leukemia (also referred as (Chronic Myelogenous Leukemia)
More than 90% of patients diagnosed with Chronic Myeloid Leukemia bear a Philadelphia chromosome t(9;22)(q34.1;q11.2), which is a reciprocal translocation between chromosome 22 (BCR locus) and chromosome 9 (ABL1 locus (1, also see OMIM). The Drug Imatinib mesylate, also known as Gleevec, was the one of the first molecularly developed drugs, and has a remarkably high success rate in treatment of patients with Chronic Myeloid Leukemia (5)
Approximately 20% of patients (25 - 30% of adult and 2 - 10% of children) diagnosed with Acute Lymphoblastic Leukemia bear a Philadelphia chromosome t(9;22)(q34.1;q11.2), which is a reciprocal translocation between chromosome 22 (BCR locus) and chromosome 9 (ABL1 locus) (1, also see OMIM). Treatment of Acute Lymphoblastic Leukemia patients with Gleevec do not have the same success as Chronic Myeloid Leukemia patients treated with Gleevec, as the genomic instability of ALL cells contribute to point mutations arising in the BRC-ABL kinase domain, leading to resistance to Gleevec (4).
Gene Overview
The ABL1 gene encodes for a non-receptor tyrosine kinase that is ubiquitously expressed and involved in a large number of cellular processes (see "NCBI Gene). A reciprocal translocation between chromosome 22 (BCR locus) and chromosome 9 (ABL1 locus) produces the Philadelphia chromosome t(9;22)(q34.1;q11.2), which is prevalent in chronic myeloid leukemia (1, 2).
Common Alteration Types
Put your text here and/or fill in the table with an X where applicable
| Copy Number Loss | Copy Number Gain | LOH | Loss-of-Function Mutation | Gain-of-Function Mutation | Translocation/Fusion |
|---|---|---|---|---|---|
| EXAMPLE: X | EXAMPLE: X | EXAMPLE: X | EXAMPLE: X | EXAMPLE: X | EXAMPLE: X |
Internal Pages
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External Links
Put your text here - Include as applicable links to: 1) Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2) COSMIC, 3) CIViC, 4) St. Jude ProteinPaint, 5) Precision Medicine Knnowledgebase (Weill Cornell), 6) Cancer Index, 7) OncoKB, 8) My Cancer Genome, 9) UniProt, 10) Pfam, 11) GeneCards, 12) GeneReviews, and 13) Any gene-specific databases.
EXAMPLES
ABL1 by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information
ABL1 by COSMIC - sequence information, expression, catalogue of mutations
ABL1 by CIViC - general knowledge and evidence-based variant specific information
ABL1 by St. Jude ProteinPaint mutational landscape and matched expression data.
ABL1 by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs
ABL1 by Cancer Index - gene, pathway, publication information matched to cancer type
ABL1 by OncoKB - mutational landscape, mutation effect, variant classification
ABL1 by My Cancer Genome - brief gene overview
ABL1 by UniProt - protein and molecular structure and function
ABL1 by Pfam - gene and protein structure and function information
ABL1 by GeneCards - general gene information and summaries
"ABL1" by NCBI Gene - general gene information
References
1. Drucker, BJ et al. (2001). Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome. NEJM 344:1038-1042 PMID 11287973. DOI: 10.1056/NEJM200104053441402
2. Faderl, S et al. (1999). The Biology of Chronic Myeloid Leukemia. NEJM 341:164-172. PMID 10403855. DOI: 10.1056/NEJM199907153410306
3. Wong S and Witte ON. (2004). The BCR-ABL story: bench to bedside and back. Annu Rev Immunol. 22:247-306. PMID 15032571 DOI: 10.1146/annurev.immunol.22.012703.104753
4. Soverini, S. et al. (2014). Drug resistance and BCR-ABL kinase domain mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia from the imatinib to the second-generation tyrosine kinase inhibitor era: The main changes are in the type of mutations, but not in the frequency of mutation involvement. Cancer 120:1002-9, PMID 24382642 DOI: 10.1002/cncr.28522
5. Druker, B. J., et al. (2001). Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. New England Journal of Medicine 344, 1031–1037. PMID 11287972 DOI: 10.1056/NEJM200104053441401
Notes
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