Singapore - Cancer biology: The good, the bad and the ugly

The interaction between good and malignant immune cells may promote blood cancer invasiveness and progression

Leukemia is the most common type of cancer in children. It is a particularly deadly form of cancer characterized by an abnormal increase of immature white blood cells. Subhra K. Biswas at the A*STAR Singapore Immunology Network and co-workers have now discovered a subset of immune cells called monocytes that become proinflammatory when cultured with leukemic cells1. More importantly, they have reasons to believe that this ‘change of state’ might be an important driver of leukemia invasiveness and progression.

Monocytes and leukemia cells are both immune cells. The difference between them is that monocytes help protect the body against pathogens, whereas leukemia cells are cancerous.

Biswas and co-workers isolated leukemia cells from patients with leukemia, and cultured them with monocytes that they obtained from the blood of healthy subjects. The monocytes that had been exposed to the leukemic cells were found to have a higher expression level of the proinflammatory chemokine protein CXCL10.

The researchers also isolated monocytes from the bone marrow of patients with leukemia, which were found to have a higher expression level of CXCL10 in comparison to monocytes from healthy subjects. In addition, the CXCL10 protein levels in the blood were higher in leukemia patients than in normal individuals.

CXCL10 is a secreted protein, so proinflammatory monocytes that express high levels of CXCL10 because of their prior exposure to leukemia cells will release the chemokine into their cell culture medium. When the researchers collected this cell culture medium and put it in one section of a cell culture dish, leukemia cells from patients readily migrated towards the medium. Blocking CXCL10 in the medium using antibodies reduced the migration of the leukemia cells towards the proinflammatory monocyte medium.

In addition, Biswas and colleagues found that CXCL10 alone could enhance leukemia cell migration. These data indicate that proinflammatory monocytes can drive leukemia by enhancing the migratory potential of leukemia cells, which may play a key role in the spread of leukemia throughout the body.

The researchers found that CXCL10 increased the expression of an enzyme in leukemia cells that enables them to chew up an extracellular net that would normally keep them in place, increasing their ability to migrate and invade. The expression of this enzyme was tightly linked to the expression of CXCL10 in patients with leukemia. The findings suggest that blockade of CXCL10 could serve as a novel therapy to treat leukemia.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network

References

1.     Lee, Y. et al. Protumoral role of monocytes in human B-cell precursor acute lymphoblastic leukemia: involvement of the chemokine CXCL10. Blood doi:10.1182/blood-2011-06-357442 (2012).