What if, even after you’ve killed every cancer cell in the body, there are still non-malignant cells left that are halfway there. That’s the conclusion of two very scary papers published in the past week[ Nature vol. 506 pp, 300 – 301, 328 – 33 ’14, Proc. Natl. Acad. Sci. vol. 111 pp. 2548 – 2553 ’14 ]. Both involve acute myelogenous leukemia (AML).
Blood cancers are easy to study even without getting samples of the marrow, which is (relatively) easy to come by. The marrow contains stem cells which can form all the cellular elements of blood (red cells, all types of white cells and platelets). They are called hematopoietic stem cells (HSCs), and just one of them is enough to completely repopulate the radiation destroyed marrow of an experimental animal.
Even a person suffering with AML contains functionally normal HSCs in their marrow (otherwise they’d be dead). What these papers show, is that these cells contain some, but not all of the mutations found in the leukemic cells (their names are DNMT3A, IDH1, IDH2, ASXL1, IKZK1 — they don’t roll trippingly off the tongue do they?). They are called preleukemic cells, and the papers show that conventional therapy for AML does NOT kill them. Essentially these cells are accidents waiting to happen.
The PNAS paper calls these genes ‘landscaping genes’, a term which may be original. I love the term, it’s extremely descriptive and short. These are genes involved in global chromatin changes — we’re talking epigenetics here — proteins causing changes in DNA and the proteins that bind to it, which don’t actually change the order of bases in the DNA.
Hopefully this doesn’t apply to other forms of cancer, but I have a sinking feeling that it does. So getting rid of every cancer cell in the body, may not be enough. Frightening.