Illustration of NOTCH signaling and glycosylation interaction in leukemia cells.

Decoding Leukemia: How NOTCH Activation Could Lead to Targeted Therapies

Jordan Keane in Health & Wellness August 2025 • 4 min read.

"Unlocking the role of glycosyltransferase expression in acute myeloid leukemia (AML) to revolutionize treatment approaches."

Acute myeloid leukemia (AML) is a complex and aggressive cancer affecting the bone marrow and blood. Scientists are constantly seeking new ways to understand and combat this disease. Recent research has shed light on the role of NOTCH signaling, a crucial pathway that regulates cell growth and differentiation, and its interaction with glycosylation, a process that modifies proteins with sugar molecules. This intersection could hold the key to developing more effective and targeted AML therapies.

NOTCH signaling plays diverse roles in regulating the growth of AML cells. Glycosylation of NOTCH receptors is known to modulate NOTCH activation. However, the specifics of NOTCH glycosylation in AML cells remain unclear. A new study has examined how ligand-induced NOTCH activation influences the expression of NOTCH-modifying glycosyltransferases, enzymes that control glycosylation, in AML cell lines.

Researchers stimulated AML cell lines, THP-1 and TMD7, with recombinant NOTCH ligands JAGGED1 and DELTA1, and then analyzed the expression levels of glycosyltransferases. The goal was to determine how NOTCH activation affects the glycosylation machinery within these cancer cells, potentially revealing new therapeutic targets.

Unveiling the Connection: NOTCH Signaling and Glycosyltransferase Expression

Illustration of NOTCH signaling and glycosylation interaction in leukemia cells.

The study revealed that stimulating AML cells with NOTCH ligands significantly impacted the expression of several glycosyltransferases. In THP-1 cells, ligand stimulation boosted the expression of POFUT1, LFNG, MFNG, RFNG, GXYLT1, GXYLT2, and XXYLT1. In TMD7 cells, the expression of RFNG and GXYLT1 was increased.

These findings suggest a direct link between NOTCH activation and the expression of glycosyltransferases in AML cells. This relationship implies that NOTCH activation can modulate its sensitivity to ligands by altering the glycosylation of its receptors.

POFUT1: Essential for NOTCH activation by adding O-fucose moieties.
LFNG, MFNG, RFNG: Fringe glycosyltransferases that add N-acetylglucosamine (GlcNAc) to O-fucose.
GXYLT1, GXYLT2, XXYLT1: Involved in adding xylose residues, potentially inhibiting NOTCH activity.

By influencing these glycosyltransferases, NOTCH activation may fine-tune its signaling pathway, creating a feedback loop that enhances or dampens its activity. This intricate control mechanism could be crucial for the survival and proliferation of AML cells.

The Future of AML Treatment: Targeting Glycosylation

This research opens new avenues for understanding and treating AML. By clarifying the relationship between NOTCH signaling and glycosyltransferase expression, scientists can explore novel therapeutic strategies that target glycosylation. Modulating NOTCH glycosylation could disrupt the signaling pathways that drive AML cell growth and survival, paving the way for more effective and less toxic treatments.

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This article is based on research published under:

DOI-LINK: 10.4081/hr.2018.7576, Alternate LINK

Title: Notch Activation Promotes Glycosyltransferase Expression In Human Myeloid Leukemia Cells

Subject: Hematology

Journal: Hematology Reports

Publisher: MDPI AG

Authors: Shichun Wang, Mai Itoh, Erika Shiratori, Mika Ohtaka, Shuji Tohda

Published: 2018-09-24

Everything You Need To Know

What roles do NOTCH signaling and glycosylation play in acute myeloid leukemia (AML)?

In acute myeloid leukemia (AML), NOTCH signaling is a pathway that regulates cell growth and differentiation. Glycosylation is a process that modifies proteins with sugar molecules. Understanding the interaction between NOTCH signaling and glycosylation could lead to the development of more effective and targeted AML therapies. Specifically, glycosylation of NOTCH receptors can modulate NOTCH activation, influencing how the cancer cells grow and proliferate.

How did researchers stimulate AML cells, and what specific ligands were used in the experiment to uncover NOTCH signaling's influence on glycosyltransferase expression?

Researchers stimulated AML cell lines, specifically THP-1 and TMD7, with recombinant NOTCH ligands JAGGED1 and DELTA1. They then analyzed the expression levels of glycosyltransferases to see how NOTCH activation affects the glycosylation machinery within these cancer cells. This helped uncover how NOTCH signaling influences glycosyltransferase expression.

What specific glycosyltransferases showed altered expression in THP-1 and TMD7 cells upon stimulation with NOTCH ligands JAGGED1 and DELTA1?

In THP-1 cells, ligand stimulation boosted the expression of POFUT1, LFNG, MFNG, RFNG, GXYLT1, GXYLT2, and XXYLT1. In TMD7 cells, the expression of RFNG and GXYLT1 increased. These glycosyltransferases play different roles; for example, POFUT1 is essential for NOTCH activation, while GXYLT1, GXYLT2, and XXYLT1 are involved in adding xylose residues, potentially inhibiting NOTCH activity.

How does NOTCH activation influence glycosyltransferases, and what implications does this have for the survival and proliferation of acute myeloid leukemia (AML) cells?

By influencing glycosyltransferases such as POFUT1, LFNG, MFNG, RFNG, GXYLT1, GXYLT2, and XXYLT1, NOTCH activation can fine-tune its signaling pathway. This creates a feedback loop that can either enhance or dampen NOTCH activity. This intricate control mechanism is crucial for the survival and proliferation of AML cells. If this mechanism is interrupted, it might become a new avenue for treatment.

How could targeting glycosylation impact future treatments for acute myeloid leukemia (AML), and what makes this approach potentially advantageous?

Targeting glycosylation by modulating NOTCH glycosylation could disrupt the signaling pathways that drive AML cell growth and survival. This approach could lead to the development of more effective and less toxic treatments for AML. By clarifying the relationship between NOTCH signaling and glycosyltransferase expression, scientists can explore novel therapeutic strategies.