New research is shedding light on how leukaemia cells can
survive cancer treatment, suggesting new possibilities for stopping
them in their tracks.
Leukaemia is cancer of the blood and it has one of the highest
cancer mortality rates. This is partly because there is a high
relapse rate, as some cancer cells can survive the initial
treatment. These surviving cells are often resistant to treatment,
allowing the cancer to spread and become fatal.
How these treatment-resistant cells survive initial chemotherapy
is not well understood. One popular theory has been that they sit
hiding in specific niches within the bone marrow that usually
harbour blood stem cells - basic cells that can become all other
blood cells.
However, new research in mice, and validated with human samples,
has revealed that certain leukaemia cells do not sit and hide.
Instead, to the researchers' surprise, the cells were scattered
throughout the mouse bone marrow both before and after treatment,
and they were moving around rapidly.
After treatment, the leukaemia cells that survived were seen
moving faster than those before treatment. The researchers suggest
that the act of moving itself may help the cells to survive,
possibly through short-lived interactions with an array of our own
cells.
The research was led by a team at Imperial College London
with colleagues from the Francis Crick Institute in London and the
University of Melbourne in Australia.
Study leader Dr Cristina Lo Celso from Imperial said: "We
expected the cells that survived treatment to be sat in particular
niches, but instead they are very active throughout the bone
marrow. We now know that it would be ineffective to target
particular niches in the bone marrow to tackle treatment-resistant
leukaemia.
"Now that we know that the cells don't hide, we can explore why
that is and how their movement helps them to survive. Ultimately we
want to find out whether we can stop the movement, and whether this
could kill the treatment-resistant cells.
"This research is still in its early stages, but we believe we
have already gained valuable insights to open up new avenues in the
development of novel, more effective leukaemia treatments."
The team's investigation of leukaemia cells' behaviour also
revealed that they actively attack bone cells, which are known to
support healthy blood production. The researchers believe this
insight could help scientists to develop treatments to safeguard
production of healthy blood cells in leukaemia patients.
Imperial's Dr Delfim Duarte said: "Our study supports the idea
that, at least in this leukaemia, new therapies should target the
cancer cells themselves instead of the surrounding normal stromal
cells to better eradicate the disease."
Dr Edwin Hawkins, now at the Walter and Eliza Hall Institute of
Medical Research in Australia, added: "Our work also suggests that
protecting normal stromal bone cells from the attack of leukaemia
cells can have wide implications in the support of healthy blood
cell production. Keeping blood cells levels up would prevent
anemia, infection and bleeding."
To investigate the working of leukaemia at the cellular level,
the team used a technique called intravital microscopy that allows
high-resolution fast imaging of live animals. The team used mice
with a particularly deadly type of leukaemia called T cell acute
leukaemia and tracked the movement of disease cells before and
after treatment.
Moreover, through collaboration with the Francis Crick Institute
and the University of Melbourne, they were able to demonstrate that
the findings hold true in human samples too.
The research was funded by the charities Bloodwise and Cancer
Research UK, alongside contributions to buy equipment and recruit
team members from the European Research Council, the Human Frontier
Science Program, and the European Hematology Association.
Dr Alasdair Rankin, Research Director at Bloodwise, said: "Most
children and adults with acute leukaemia respond well to
chemotherapy initially, but one of the biggest challenges we face
is the cancer returning. Although this is early work, these
significant findings reveal that stopping cancer cells moving
around the bone marrow may be a more targeted way to treat acute
leukaemia, and could tackle resistant disease."
Dr Emma Smith, science communications manager at Cancer Research
UK, said: "Shedding light on what's happening in the bone marrow
could open up new approaches to prevent leukaemia cells becoming
resistant to treatment, which makes the disease much harder to
treat. This interesting study could also be a starting point for
developing new treatments that help leukaemia patients by restoring
the normal functions of their bone marrow, such as protecting from
infections."
The paper 'T-cell acute leukaemia exhibits dynamic
interactions with bone marrow microenvironments' is published
in Nature.