How ‘chameleon cancers’ can change color to survive treatment

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A Wright-stained smear of bone marrow aspirate from a patient with precursor B-cell acute lymphoblastic leukemia. Credit: VashiDonsk/Wikimedia/CC BY-SA 3.0

An international team of scientists has discovered one of the mechanisms that explains how some leukemias evade treatment by changing their appearance and identity.

Most children with B-cell acute lymphoblastic leukemia (ALL), a common blood cancer, have benefited from great improvements in treatment over the past 50 years, and nine out of 10 children diagnosed will now be cured.

For those whose leukemia does not respond to treatment, much hope has been pinned on new treatments based on antibodies and immune cells, such as CAR T cells, that specifically target the surface of leukemia cells.


Doctors, however, have found that some of these leukemias can evade immune therapies by stopping production of the cell-surface proteins these therapies target, or even changing to become a different type of cancer. which these new treatments are ineffective.

This is a particular problem for leukemias caused by genetic rearrangements involving a gene called MLL.

Teams from the University of Newcastle, UK, the Princess Máxima Center in Utrecht and the University of Birmingham have now revealed one of the mechanisms that explains how these chameleon cancers change their appearance and identity.

Posting in the newspaper Bloodhave studied this behavior of cell identity change in leukemias caused by the MLL/AF4 fusion gene.

Dr Simon Bomken, MRC Clinical Scientist and Honorary Consultant at Newcastle University and co-senior author of the paper, said: “It has long been known that ALL cells carrying this chromosomal rearrangement can relapse as a different type of cancer. blood, acute myeloid leukemia (AML) When this change occurs, the leukemia becomes extremely difficult to treat.

“By studying the MLL/AF4 leukemias, we showed that the change can occur in blood cells throughout different stages of development in the bone marrow.

“Importantly, the change may be the result of additional genetic changes that may be caused by the chemotherapy itself. As a consequence, some leukemias completely ‘reprogram’ themselves, changing identity from one cell type to another.”

The team found that this reprogramming may be driven by changes in master control genes, including CHD4, which is normally required to turn off genes important for AML development.

important implications

Dr Bomken, Honorary Consultant Pediatric Oncologist at Newcastle Hospitals, added: “These results have important implications for our understanding of disease development and response to therapy.

“They are beginning to allow us to identify which patients are most at risk of relapse, which informs the choice of which treatments to use and when.

“Over time, specific therapies may become available to help prevent or overcome leukemic change and prevent the chameleon from changing color.”

Blood Cancer Cures and Care: Approaching Leukemia and Lymphoma

More information:
Ricky Tirtakusuma et al, Direct lineage switching of epigenetic regulatory genes in MLL/AF4 leukemia, Blood (2022). DOI: 10.1182/blood.2021015036

Diary information:

Provided by Newcastle University

Citation: How ‘Chameleon Cancers’ Can Change Their Colors to Survive Treatment (Oct 31, 2022) Retrieved Oct 31, 2022 from treatment.html

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