Target intelligence / Profile preview

Abelson murine leukemia viral oncogene homolog 1 messenger RNA (ABL1 mRNA) (ABL1 mRNA)

Target
ABL1 mRNA
Molecular classification
Messenger RNA, Nucleic acid, Proto-oncogene transcript
01

Overview

ABL1 mRNA is the messenger RNA transcript of the Abelson murine leukemia viral oncogene homolog 1 gene, which encodes a non-receptor tyrosine kinase essential for cellular processes such as growth, survival, and DNA damage response (NCBI Gene, ID: 25). In hematological malignancies, most notably Chronic Myeloid Leukemia (CML), the ABL1 gene undergoes a reciprocal translocation with the BCR gene to form the BCR-ABL1 fusion gene, resulting in a chimeric mRNA that translates into a constitutively active oncoprotein (UniProt, P00519). This mRNA is a critical therapeutic target for emerging RNA-based modalities, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), which aim to degrade the transcript and silence the oncogenic signal at the pre-translational level (PubMed, PMID: 25613577). While current clinical standards utilize tyrosine kinase inhibitors (TKIs) like Imatinib to target the protein product, mRNA-directed therapies are being investigated to bypass resistance caused by kinase domain mutations (PubMed, PMID: 30232345). Furthermore, the precise quantification of BCR-ABL1 and ABL1 mRNA levels via real-time quantitative PCR is the gold standard for monitoring treatment efficacy and detecting minimal residual disease in clinical practice (NCCN Guidelines, 2024).

Other names
c-ABL mRNAABL mRNAProto-oncogene c-Abl mRNABCR-ABL1 fusion mRNAJTK7 mRNAAbelson tyrosine-protein kinase 1 mRNA
02

Mechanism of action

RNA interference (RNAi) or antisense-mediated RNase H cleavage of the mRNA transcript to prevent the translation of the ABL1 or BCR-ABL1 tyrosine kinase protein; alternatively, the mRNA serves as the template for protein products targeted by competitive and allosteric tyrosine kinase inhibitors.

03

Biological functions

Protein synthesis templateSignal transduction regulationCell cycle controlDNA damage response coordinationApoptosis regulation
04

Disease associations

Chronic Myeloid Leukemia (CML)Acute Lymphoblastic Leukemia (ALL)Philadelphia chromosome-positive (Ph+) leukemiaSolid tumors (overexpression context)
05

Safety considerations

Off-target silencing of physiological ABL1 transcripts required for DNA repairSystemic delivery challenges to hematopoietic stem cellsPotential for sequence-specific resistance mutations in the mRNA target siteHematological toxicities including myelosuppression
06

Interacting drugs

Antisense oligonucleotides (experimental)

7 more in the full profile.

07

Biomarkers

BCR-ABL1 transcript levels (International Scale)ABL1 transcript levels (internal reference)Major Molecular Response (MMR)Deep Molecular Response (DMR)Complete Molecular Response (CMR)

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