A scary paper: Cancer by proxy

Can a good kid growing up in a bad neighborhood turn bad? Most think so. What about a genetically normal cell growing up in a bad neighborhood? Can it turn cancerous if its neighbors have a mutation ? A recent paper [ Nature vol. 539 pp.304 – 308 ’16b] demonstrates how this can happen.

A gene called PTPN11 is mutated in myelomonocytic leukemia (MML)in humans and mice. Expressing the mutant in blood cells causes leukemia in mice (nothing spectacular there).

However, expressing the mutant in marrow supporting cells, not blood cells or blood stem cells for long enough gives MML in mice which can be transplanted into normal mice producing MML there.

Note that the blood stem cells don’t contain the mutant gene. One theory has it that mutant PTPN11 recruits monocytes, which then produce other stuff (CCL3 also known as MIP1alpha and interleukin1Beta), which then turns on blood stem cells to proliferate madly causing leukemia. Giving a CCL3 receptor antagonist reverses the myeloproliferation (but it isn’t clear to me if it reverses the leukemia once established)

As far as we know the cells developing into MML don’t contain mutant PTPN11. So it’s cancer by proxy. Obviously some changes (mutations, epigenetic changes) have have occurred in the leukemic cells, but at this point we don’t know what they are.

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