Chloroquine triggers Burkitt lymphoma

Burkitt lymphoma is is a form of non-Hodgkin's lymphoma in which cancer starts in immune cells called B-cells. The disease characteristically involves the jaw or other facial bone, distal ileum, cecum, ovaries, kidney, or breast. Recognized as the fastest growing human tumor, Burkitt lymphoma is associated with impaired immunity and is rapidly fatal if left untreated.

Burkitt lymphoma was first identified in 1956 among children in Africa. Since a couple of variants exist, the endemic variant is also called the African variant. Burkitt lymphoma is common in young children who also have malaria and Epstein-Barr, the virus that causes infectious glandular fever (mononucleosis).

One possible mechanism may be that malaria weakens the immune system's response to Epstein-Barr, allowing it to change infected B-cells into cancerous cells. About 98% of African cases are associated with Epstein-Barr infection. But suppose it's the other way around: it is entirely possible that drugs to treat or prevent malaria could be the culprit.

A protozoan parasite, Plasmodium falciparum, is just one of the species of Plasmodium that cause malaria in humans. It is transmitted by a female Anopheles mosquito. The parasite is resistant to chloroquine treatment except in Haiti, the Dominican Republic, parts of Central America and parts of the Middle East. But in some regions Plasmodium falciparum regained susceptibility to chloroquine.

Trials to reintroduce chloroquine into parts of Africa are underway. However, because there are concerns about whether chloroquine increases replication of the Epstein-Barr virus, thereby contributing to the development of endemic Burkitt lymphoma[1].

It is therefore of the utmost importance to research if that connection really exists. Novel research found that chloroquine indeed drives Epstein-Barr virus replication and in turn might trigger Burkitt lymphoma[2].

But if there's one, there might be more. Research also shows that chloroquine may be involved in the enhancement of replication of other viruses. A study demonstrated that chloroquine indeed enhances Semliki Forest virus and encephalomyocarditis virus replication in mice[3].

[1] Karmali et al: Chloroquine enhances Epstein-Barr virus expression in Nature – 1978
[2] Li et al: Chloroquine triggers Epstein-Barr virus replication through phosphorylation of KAP1/TRIM28 in Burkitt lymphoma cells in Plos Pathogens – 2017. See here.
[3] Maheshwari et al: Chloroquine enhances replication of Semliki Forest virus and encephalomyocarditis virus in mice in Journal of Virology – 1991