Matt Kaiser
Posted by
Matt Kaiser

Researchers shed light on how blood cancers start and resist treatment

Matt Kaiser
Posted by
Matt Kaiser
16 Nov 2016

Our researchers are shedding light on how blood cancers start and behave and are using this knowledge to tackle these diseases in new ways.

Here are three highlights from the past month.

Tracking leukaemia cell movement

It’s thought that leukaemias may come back after treatment because a few hardy cells survive and grow back. Exactly how they do this and what makes a cell resistant is not well known. Rather than just looking at the leukaemia cells themselves, scientists have recently turned their attention to the neighbourhood where the cells develop – in the case of leukaemia, the bone marrow. It contains a dynamic mix of healthy cells and tissues, like blood vessels and many types of immune cells, and this network can be recruited by the cancer to support growth and evade treatment. Researchers thought that some leukaemia cells could dodge being killed by chemotherapy by hiding away in this protective niche.

Different colours show different environments in the bone marrow. Credit: Edwin Hawkins and Delfim Duarte, Imperial College London

But new research from Dr Cristina Lo Celso’s team at Imperial College London, showed something quite surprising. Using sophisticated microscopy to track individual acute lymphoblastic leukaemia (ALL) cells in mice, they found that cells that survived treatment actually moved about faster than those killed. And the more intense the treatment, the quicker they moved. The researchers think the ALL cells could be aiding their survival through short-lived interactions with lots of other cells in the bone marrow. If these touchpoints can be blocked or the cells hindered in their movement through the bone marrow, then this could be the basis of a new approach to treatment that eliminates even the hardiest of leukaemia cells. The Imperial team have since shown that leukaemia cells behave the same way in patients, which supports this idea.

“Now that we know that the cells don’t hide, we can explore why that is and how their movement helps them to survive.” Dr Cristina Lo Celso

You can read more here, and from Cancer Research UK who jointly funded the work.

Dual-pronged attack on leukaemia

Chronic lymphocytic leukaemia (CLL), the most common form of leukaemia, is currently incurable with drugs – the only hope of a cure being a gruelling stem cell transplant, which isn’t suitable for many patients who are older or have other health problems. Recently, however, new targeted drugs have been developed that have shown promise in early stage clinical trials in driving the disease into remission. The drugs hit specific signals in the leukaemia cells, part of the B-cell receptor (BCR) pathway, which typically leads to cancer cell death. But these drugs do not provide a cure and patients can eventually become resistant to treatment, leading to relapse.

Bone marrow smear showing CLL. Credit: Spike Walker, Wellcome Images

Dr Andy Steele and his team at the University of Southampton wanted to find ways to stop this happening. They already knew that one of the reasons CLL cells can avoid the effects of the treatment is by retreating from the blood to the bone marrow, spleen or lymph node, where they are protected by surrounding cells through ‘stay alive’ signals.

The scientists took a new drug called cerdulatinib, which jams two key signals in cells that promote cancer cell growth, called Syk and JAK. They found that treating CLL cells with this drug in the lab blocked the cell growth signals and the protective effect from surrounding tissues, triggering the cells to self-destruct. They observed that part of the BCR pathway known as BCL-2 was unaffected, so they added another drug that targets BCL-2, called venetoclax, and this was boosted the CLL cell self-destruction. The researchers aim to explore this effect further until it’s ready to ultimately test in patients.

This research shows how precision medicine is being driven by understanding the detailed biology of a cancer, and developing treatments to hit the disease from all angles.

“These findings give us hope that combining two drugs could combat treatment resistance” Professor Andy Steele

You can read more here.

How a common virus triggers lymphoma

Some non-Hodgkin lymphomas, such as Burkitt lymphoma, can be triggered by a virus called Epstein-Barr virus. But what goes wrong with the cell’s machinery has been something of mystery.

Epstein Barr virus infecting cells. Credit: National Cancer Institute

Now, Professor Michelle West’s team at the University of Sussex, has revealed how the virus hijacks control of two genes that have a central role in regulating cell division and death. It takes command of control centres on the cell’s DNA to dial up the activity of a gene called Myc, which stimulates cell multiplication, and dials down another called BCL2L11, a gene that normally triggers cell death and prevents cancer formation.

The team showed that blocking BCL2L11 with a drug in cells in the lab reversed this, and led to lymphoma cell death. It’s early days, but these results could open up new avenues for developing targeted treatments in virus-driven lymphomas.

“This research can guide the design of new treatments to target the disease.” Professor Michelle West

You can read more here.

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