Leukaemia is characterised by an uncontrolled growth of abnormal blood cells in the bone marrow (BM).
Escape of the cancerous cells to other organs is linked with worst disease prognosis and less susceptibility to therapy, and, as consequence, to understand the mechanism(s) behind such migration is crucial. And now, in an advance online publication of the journal "Blood", a group of researchers has found that FLT-1 - a molecule implicated in blood vessel growth – is necessary for the escape of the leukaemia cells from the BM, suggesting that blocking of this molecule might be used in the treatment of leukemia.
Leukaemia, or cancer of the white blood cells, affects 4 out of 100,000 people worldwide and in the United States alone more than 2,000 children and 27,000 adults are diagnosed with the disease every year. The illness originates from an abnormal multiplication of the cancerous cells in the BM that leaves little no space for normal blood cells to grow resulting in an impaired immune system that, among other problems, is incapable of efficiently fight infection.
It is known that leukaemia development, like it happens with solid tumours, depends on the development of extra blood vessels (a process known as vascularisation), which serve to supply the fast multiplying cancerous cells with nutrients and help rapid cancer expansion and often metastasis formation. Interestingly, it has also been found that molecules involved in vascularisation seem to be capable of act directly on the cancerous cells. One such example is VEGF (Vascular Endothelial Growth Factor) that appears to affect division, survival and migration of cancer cells and consequently cancer growth and dissemination.
FLT-1 or “Vascular endothelial growth factor receptor”, which binds to VEGF, is another molecule involved in vascularisation that has been suggested to have a role in the division and migration of cancer cells. This observation, together with the fact that FLT-1 is produced in high quantities by leukaemia cells, have led Rita Fragoso, Teresa Pereira, Sérgio Dias and colleagues in Portugal and the United States to investigate the role of FLT-1 in this disease.
For that the group of investigators used cells from patients with ALL, the most common childhood leukaemia, and one in which the abnormally proliferating cells are immature blood cells called lymphoblasts. Cells from different ALL patients, which produced distinct amounts of FLT-1, were injected into mice with no blood cells and followed in order to understand how different quantities of this molecule could affect cell fate and disease progression.
What they found was that FLT-1 levels influenced both migration and cell survival, and therefore also disease outcome.