05 November 2018

A significant number of patients whose acute myeloid leukaemia (AML) relapses after having a stem cell transplant could be experiencing cancer in “stealth mode”, new US research has found.

Scientists from Washington University School of Medicine in St Louis, Missouri, have found that in about half of people whose AML returns after a stem cell transplant, the leukaemia cells have reduced expression of genes which would allow them to be recognised by the immune system.

It means the leukaemia cells lack proteins that the stem cell donor's T cells normally use to identify them, and so are able to regrow in what the team call “stealth mode”, becoming invisible to the immune system.

Senior author Dr John DiPersio, director of the Division of Oncology at the School of Medicine, said he was surprised by the findings.

“There's a rational explanation, since the way stem cell transplants attack leukaemia - through an immunologic mechanism - is going to favour the survival of cancer cells that become invisible to the immune system,” he added.

The study, published in the New England Journal of Medicine, involved the sequencing of DNA and RNA from AML cells from 15 patients who relapsed after stem cell transplants, and from 20 AML patients who relapsed after chemotherapy.

There was little difference in the mutations present in the leukaemia cells between the two sets of relapsed AML samples, and no genes which control immune recognition were disabled by mutations.

But there was a significant difference in gene expression – which genes are active and to what degree – in half of the cases where AML relapsed following stem cell transplant. These leukaemia cells showed massively reduced production of ‘major histocompatibility complex (MHC) class II’ proteins, which the immune system would normally use to recognise malignant cells.

In addition, when leukaemia cells from patients' relapse were treated with interferon gamma, the previously invisible immune markers were revealed once again. Dr DiPersio and the team say that this presents new therapeutic possibilities for AML patients whose disease relapses in this way.

Source: Christopher, M.J., Petti, A.A., Rettig, M.P., Miller, C.A., Chendamarai, E., Duncavage, E.J., Klco, J.M., Helton, N.M., O'Laughlin, M., Fronick, C.C., Fulton, R.S., Wilson, R.K., Wartman, L.D., Welch, J.S., Heath, S.E., Baty, J.D., Payton, J.E., Graubert, T.A., Link, D.C., Walter, M.J., Westervelt, P., Ley, T.J., DiPersio, J.F. (2018) “Immune escape of relapsed AML cells after allogeneic transplantation”, New England Journal of Medicine, available at doi: 10.1056/NEJMoa1808777


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