08 April 2019

Researchers investigating acute erythroid leukaemia have identified five sub-groups of the condition that have distinct gene mutations and patient outcomes.

The diagnostic criteria for acute erythroid leukaemia have changed over the decades, and the genetic basis of the disease has been uncertain. To better understand the condition, Dr Charles Mullighan of St. Jude Children's Research Hospital in Memphis, Tennessee, USA, and colleagues carried out a large genomic analysis.

They compared the genetics of 159 childhood and adult patients with 1,903 patients with non-erythroid myeloid disorders. They were able to define five age-related sub-groups: adult TP53 mutated, NPM1 mutated, KMT2A mutated/rearranged, adult DDX41 mutated, and paediatric NUP98 rearranged. However, 37% of the cases they studied fell into an ‘other’ category, lacking a recurring identifiable mutation.

The team added that each type’s genetic features influenced the patient outcomes. For example, those in the TP53 mutated subgroup have a dismal prognosis, whereas more than 87% of those with mutations in the NPM1 gene were long-term survivors.

Overall, 45% of patients in the study had mutations in signalling pathways which could be targeted with existing drugs. This raises the possibility that genetic analysis of acute erythroid leukaemia could not only help determining prognosis but could also direct ‘precision medicine’.

Publishing their study in the journal Nature Genetics, the team writes: “This genomic landscape of acute erythroid leukaemia provides the framework for accurate diagnosis and risk stratification of this disease, and the rationale for testing targeted therapies in this high-risk leukaemia.”

Dr Mullighan said: “Genomic alterations and gene expression profiles were the strongest predictors of outcome in patients with acute erythroid leukaemia, which suggests they should be incorporated into the diagnostic and prognostic criteria.

“These results mark a new era in understanding and treatment of acute erythroid leukaemia, an aggressive leukaemia that has been plagued by diagnostic controversy and poor outcomes.”




Iacobucci, I., Wen, J., Meggendorfer, M., Choi, J.K., Shi, L., Pounds, S.B., Carmichael, C.L., Masih, K.E., Morris, S.M., Lindsley, R.C., Janke, L.J., Alexander, T.B., Song, G., Qu, C., Li, Y., Payne-Turner, D., Tomizawa, D., Kiyokawa, N., Valentine, M., Valentine, V., Basso, G., Locatelli, F., Enemark, E.J., Kham, S.K.Y., Yeoh, A.E.J., Ma, X., Zhou, X., Sioson, E., Rusch, M., Ries, R.E., Stieglitz, E., Hunger, S.P., Wei, A.H., To, L.B., Lewis, I.D., D'Andrea, R.J., Kile, B.T., Brown, A.L., Scott, H.S., Hahn, C.N., Marlton, P., Pei, D., Cheng, C., Loh, M.L., Ebert, B.L., Meshinchi, S., Haferlach, T., Mullighan, C.G. (2019) “Genomic subtyping and therapeutic targeting of acute erythroleukemia”, Nature Genetics, available from doi: 10.1038/s41588-019-0375-1