22 February 2021

Scientists have investigated the genetic changes that can trigger cancer therapy-related myeloid neoplasms in children.

Until now, the cancerous and inherited genetic changes that drive therapy-related myeloid cancers in children have not been described in detail, the US researchers say.

The research team was co-led by Drs Xiaotu Ma and Jeffery Klco from St. Jude Children's Research Hospital in Memphis, Tennessee, and Professor Tanja Gruber from Stanford University School of Medicine.

They used whole-genome and RNA sequencing to examine the genomic profile of 84 patients with a therapy-related myeloid neoplasm: 56 with acute myeloid leukaemia, and 28 with myelodysplastic syndrome. The children’s original cancers were either leukaemia, solid tumour or brain tumour, and were treated with different types of chemotherapy.

The team wrote in Nature Communications that: "Paediatric therapy-related myeloid neoplasms occur in children after exposure to cytotoxic therapy and have a dismal prognosis."

They identified a number of genetic drivers of these cancers, including mutations in the Ras/MAPK pathway, and changes in the genes RUNX1, TP53 and KMT2A.

Unlike therapy-related myeloid neoplasms in adults, the team found that those in children tended to be caused directly by cytotoxic therapy, rather than having pre-existing clones from the original cancer that grow after initial therapy.

Dr Klco said: “One thing that we've known for a long time is once kids develop this secondary tumour, the outcome is really poor.

“The alterations that drive these tumours are different in children than they are in adults, underscoring the need to study these tumours specifically in paediatrics.”

Co-author Dr Xiaotu Ma added: “This work indicates that we can detect this type of malignancy early, to study if preventative therapies could benefit patients.”


Source:

Schwartz JR, Ma J, Kamens J, Westover T, Walsh MP, Brady SW, Robert Michael J, Chen X, Montefiori L, Song G, Wu G, Wu H, Branstetter C, Hiltenbrand R, Walsh MF, Nichols KE, Maciaszek JL, Liu Y, Kumar P, Easton J, Newman S, Rubnitz JE, Mullighan CG, Pounds S, Zhang J, Gruber T, Ma X, Klco JM. (2021) “The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms.” Nature Communications, doi: 10.1038/s41467-021-21255-8

 

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