Researchers show how leukemia cells 'hide' from treatment

by Leukaemia UK

edited by Lisa Lock, reviewed by Andrew Zinin

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In a first-of-its-kind study collaboration, new research has uncovered that chronic lymphocytic leukemia (CLL) cells may switch between different survival signals, helping explain why treatments work well for some patients but stop working for others. These findings could ultimately help pave the way for more personalized treatment.

Simon Mitchell, a professor at the University of Sussex and a Leukemia UK John Goldman Fellow Follow-up Fund recipient, developed sophisticated computer models to predict how CLL cells from different patients would respond to signals that help them survive.

The research, led by Mitchell's collaborators professors Andrea Pepper and Chris Pepper and Dr. Kennedy and published in the journal Blood, could help scientists better understand why some patients respond particularly well to certain treatments while others develop drug resistance.

This is the first time a detailed computer model of B-cell receptor (BCR) signaling in CLL has been directly tested and supported using cells from patients.

CLL is the most common adult leukemia and remains incurable and a lifelong condition. Advances in therapies known as Bruton's tyrosine kinase inhibitors (BTKi) have significantly changed outcomes for patients over the years, but responses can vary.

These drugs disrupt an important communication system used by CLL cells called the B-cell receptor (BCR) pathway. This forces cancer cells out of protective areas such as the lymph nodes, where they "hide," and into the bloodstream, allowing them to be targeted more effectively.

However, some patients eventually develop resistance to treatment. While mutations can explain resistance in some cases, for 20% to 30% of patients who relapse, the reason remains a mystery, with no detectable mutations that would explain why their cancer has become resistant.

Using Mitchell's model, the researchers uncovered that CLL cells can use two different communication pathways to survive. The team found that when the usual B-cell receptor (BCR) pathway is blocked by inhibitors, some CLL cells can use a second pathway, called Toll-like receptor 9 (TLR9), to continue to evade treatment.

This offers a new explanation for why some patients develop resistance to treatment, while others respond exceptionally well.

The findings could help scientists and clinicians better understand treatment resistance and, for patients, this could ultimately mean identifying an effective drug or drug combination earlier while avoiding treatments that are unlikely to work. It could also reduce unnecessary side effects, treatment toxicity and time spent in the hospital.

Mitchell said, "Therapies targeting BCR signaling have transformed the treatment of CLL, but we still don't fully understand why they work so well for some patients and eventually stop working for others.

"Our research suggests that CLL cells may be able to change the signals they rely on to survive. Understanding these differences could ultimately help us better predict how patients will respond to treatment."

Andrea Pepper said, "Combining laboratory experiments with mathematical models revealed insights neither approach could have achieved alone. Our findings not only pinpoint which CLL patients need an additional drug alongside BTK inhibitors, but provide clear clues on where to focus next to develop new, targeted therapies for these individuals."

Dr. Simon Ridley, director of research and advocacy at Leukemia UK, said, "We're proud to support innovative researchers such as professor Mitchell. Patients with the same diagnosis can respond very differently to the same treatment and, for people with blood cancer, finding the right treatment at the right time is vital.

"This groundbreaking new modeling is an exciting example of how technology could help us understand those differences in response and move toward a more personalized treatment plan for patients."

Publication details

Emma Kennedy et al., TLR9-dependent migration identifies different Chronic Lymphocytic Leukemia signaling states under BTK inhibition., Blood Journal (2026). DOI: 10.1182/blood.2025032914

Journal information: Blood

Key medical concepts

Chronic Lymphocytic LeukemiaDrug Resistance

Clinical categories

Oncology Provided by Leukaemia UK Who's behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →

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Citation: Researchers show how leukemia cells 'hide' from treatment (2026, October 22) retrieved 22 October 2026 from https://medicalxpress.com/news/2026-10-leukemia-cells-treatment.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.