29 Jul 2026 Research

Research Blog: A new target for paediatric AML

In May this year one of our Leukaemia UK funded John Goldman Fellows, Dr Noelia Che, published a new paper along with her colleagues: MCL1 inhibition to enhance the efficacy of MYB targeting in paediatric acute myeloid leukaemia  

Dr Noelia Che

In this blog is a breakdown of the research paper. 

Despite being the most prevalent cancer in children, over the past few decades the survival outcome for children with leukaemia has improved dramatically. This progress has been driven by better chemotherapy, targeted treatment and better disease understanding, and the use of bone marrow transplantation when needed.  

Despite these advances, acute myeloid leukaemia (AML) remains one of the most difficult childhood leukaemia’s to treat. Around 70-75% of children survive initially, but many experience a relapse after chemotherapy, meaning the leukaemia returns. Increasing the intensity of chemotherapy is unlikely to improve survival further, because higher doses also increase serious side effects and long-term treatment complications.  

Particularly for children, intensive chemotherapy can have a profound and lifelong impact on their health. While it is often successful in treating the leukaemia, it can also damage healthy cells and organs, leaving some patients with long-term complications. These can include fertility problems, chronic lung damage causing breathing difficulties, and heart damage that may lead to serious cardiac conditions, with some patients even requiring a heart transplant later in life. 

For this reason, researchers are focusing on developing targeted therapies. Unlike chemotherapy, which attacks all rapidly dividing cells, targeted therapies aim to interfere with specific molecules that leukaemia cells rely on to survive, while having less effect on healthy cells. 

One important target is a protein called MYB, which was the focus of Dr Noelia Che’s Leukaemia UK John Goldman Fellowship. MYB is a transcription factor, meaning it acts like a switch that turns groups of genes on or off. In healthy bone marrow, MYB helps control the growth and development of blood cells. However, AML cells become unusually dependent on MYB because it continuously activates genes that promote leukaemia cell growth and prevent the cells from maturing normally. Since leukaemia cells rely much more heavily on MYB than normal blood cells do, disrupting MYB activity may selectively harm leukaemia cells while sparing healthy tissue. 

Unfortunately, MYB itself is difficult to block with conventional drugs because its structure does not provide many places for medications to bind. Instead, researchers have explored indirect ways of targeting MYB, such as preventing it from interacting with other proteins that help it function or encouraging the cell to destroy the MYB protein altogether. 

One promising drug is mebendazole, a medication that has been safely used for many years to treat parasitic worm infections. Dr Che and her colleagues identified mebendazole as a potential AML treatment using computer-based analyses that compared gene activity patterns in leukaemia cells with the effects of thousands of existing drugs. They found that mebendazole rapidly reduces the amount of MYB protein inside AML cells by promoting its breakdown through the cell‘s’ natural protein recycling system, known as the proteasome. The proteasome acts like the cell‘s’ waste disposal and recycling centre, breaking down proteins that are damaged or no longer needed. Because MYB is naturally a short-lived protein and AML cells depend heavily on maintaining high MYB levels, accelerating MYB breakdown causes leukaemia cells to lose an essential survival signal and die. 

Since then other studies have shown that mebendazole is effective against many different types of AML cells. Although it appears to influence several cellular pathways, evidence suggests that reducing MYB levels is one of the key reasons it suppresses leukaemia growth. Mebendazole has also been shown to work well alongside standard chemotherapy drugs, making it an attractive candidate for combination treatment. 

More recently, Dr Che and her colleagues have investigated combining mebendazole with newer targeted therapies rather than chemotherapy. One such target is MCL1, a member of the BCL-2 family of proteins. These proteins regulate apoptosis, which is the cell’s built-in process for removing damaged or unwanted cells. Some BCL-2 family proteins encourage apoptosis, while others prevent it. MCL1 belongs to the protective group and acts like a bodyguard, helping leukaemia cells avoid self-destruction even when they are damaged or stressed. 

Drugs that inhibit MCL1 remove this protection, making leukaemia cells much more likely to undergo apoptosis. When MYB levels are simultaneously reduced by mebendazole, leukaemia cells lose both the signals that promote their growth and one of their main survival mechanisms. This combination places the leukaemia cells under much greater stress than either treatment alone, leading to enhanced anti-leukaemia activity. 

Because therapies that trigger apoptosis have already shown significant clinical success in blood cancers, combining mebendazole with MCL1 inhibitors represents a potential new treatment strategy for children with AML. This approach aims to improve outcomes by specifically targeting the biological pathways that leukaemia cells rely on, while potentially avoiding the increased toxicity associated with more intensive chemotherapy. 

It is important to note that this research is still in early stages, but it shows one of the many routes that researchers like Dr Che are working to fight leukaemia through new strategies, repurposed medications and innovative combinations.  

Not enough? Read the full paper here.