Vicky F
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What are leukaemia stem cells and why are they important?

Vicky F
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14 Jun 2015

This weekend, I've been attending the European Haematology Association (EHA) annual conference in Vienna, Austria and blogging about some exciting topics and developments in leukaemia research.

All leukaemias are thought to originate from a single blood stem cell in the bone marrow, which has damaged DNA.  This causes the cell to abnormally divide, filling the circulatory system with immature, dysfunctional blood cells, suppressing the rest of the blood system and giving rise to leukaemia.  The cells which start the entire problem, and stay in the bone marrow are termed Leukaemia Stem Cells (LSCs).

The study of LSCs is particularly important, not just to understand how leukaemia happens in the first place, but to also understand why people relapse after treatment initially gets them into remission. LSCs are often able to hide from treatment in the bone marrow, as it's more difficult for the drugs to reach cells in the bone marrow in comparison to the ones in the circulation.  For this reason, some people considered to be at 'high risk' of relapse are given bone marrow transplants, where all of their blood stem cells, healthy or leukaemic are replaced with those from a healthy donor, or with normal blood stem cells from the individual themselves.

Speaking at the EHA meeting this week in Vienna, Austria, Ravi Majeti, a researcher into normal blood stem cells and LSCs from Stanford University, USA provided insight into how these cells work.  He and his team analysed the DNA mutations causing acute myeloid leukaemia, but also looked at healthy blood stem cells from the same person, comparing the mutations found in the two types of cells.  Professor Majeti reported that an average of five mutations in bits of DNA important for controlling blood cell growth were needed before the cell became leukaemic in AML.  Worryingly, some of the healthy blood stem cells in these patients had three or four of these mutations, showing that although not leukaemic yet, these cells were on a slippery slope to causing leukaemia if they survived treatment and their DNA became more damaged (pre-leukaemic stem cells).

We know about many of these mutations that are considered to be pre-leukaemic, not enough to cause leukaemia, but the first step towards it. For example the fusion protein AML1/ETO, which I studied during my PhD, and also TEL/AML1, a common pre-leukaemic mutation which we know is not enough to cause leukaemia, as it can be detected in children at birth, some of whom eventually go on to develop ALL many years later.

What is less well known at the moment, is how LSCs contribute to relapse.  There was recently a sad case of a man who was successfully treated aged four for a type of ALL which had the BCR/ABL fusion protein.  However 22 years later, he relapsed and eventually died after treatment was unsuccessful.  Scientists found that an LSC from his original leukaemia had been hiding asleep in his bone marrow for over two decades, before eventually getting more damaged DNA leading to his relapse. 

Thankfully relapse after this long is very rare, but it highlights the importance of properly understanding LSCs to improve outcome for patients and to come up with better therapies.



Great blog Vicky!

As someone who's been through it all and (touch wood) come out of the other side it's fascinating to hear how we're getting closer to understanding more about how leukaemia actually begins. Fingers crossed that we can pick it up at this pre-leukaemic phase in the future and knock it on the head before it develops.

I hope you're well and enjoyed the rest of the conference?