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Exploiting the Notch pathway in HTLV-1-driven adult T-cell leukemia/lymphoma: a mini-review
Mohammad Mehdi Akbarin1,2, Zahra Farjami1,3, Hugo Ramírez Álvarez4
1Virology, Genetics, and Molecular Biology Laboratory, Faculty of Higher Studies Cuautitlán, Veterinary Medicine, Campus 4, National Autonomous University of Mexico, Cuautitlán-Teoloyucan Highway, Km. 2.5, San Sebastián Xhala, Cuautitlan Izcalli, 54714, Mexico.
Annals of Hematology
|May 27, 2026
Summary
Human T-cell leukemia virus type 1 (HTLV-1) hijacks Notch signaling, a critical pathway for T-cell function, to drive adult T-cell leukemia/lymphoma (ATLL) development. Targeting Notch shows promise but faces clinical challenges.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and inflammatory diseases.
- The precise molecular mechanisms of HTLV-1 pathogenesis are not fully understood.
- Notch signaling is crucial for T-cell biology, immune evasion, and leukemogenesis.
Purpose of the Study:
- To review the role of Notch signaling in HTLV-1 infection and ATLL pathogenesis.
- To discuss the therapeutic strategies targeting the Notch pathway in HTLV-1-associated malignancies.
Main Methods:
- Review of existing literature on HTLV-1, Notch signaling, and ATLL.
- Analysis of molecular mechanisms involving HTLV-1 proteins (Tax, HBZ) and Notch pathway components.
- Evaluation of preclinical and clinical data on Notch-targeted therapies.
Main Results:
- HTLV-1 proteins modulate Notch activity, leading to constitutive activation and oncogenic transformation.
- Mutations in NOTCH1 and FBXW7 stabilize Notch signaling, promoting proliferation and survival.
- JAG1 overexpression and crosstalk with PI3K/STAT3 pathways contribute to Notch-driven ATLL phenotypes.
- Preclinical inhibition of Notch reduces ATLL cell growth, but clinical efficacy is limited.
Conclusions:
- Notch signaling is a key player in HTLV-1-driven leukemogenesis.
- Targeting Notch offers therapeutic potential for ATLL, but challenges remain.
- Further understanding of Notch pathway intricacies is needed for effective interventions.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
01:51Mechanisms of Retrovirus-induced Cancers
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...