Study identifies risk for some childhood cancer patients developing secondary leukaemia 研究確定了一些兒童癌症患者發展為繼發性白血病的風險

Editor’s note: The study report certainly acknowledges that chemotherapy for neuroblastoma can cause leukemia. It’s uncertain though how long it would take for a neuroblastoma patients who receive chemotherapy to develop the secondary leukemia.

The study screened DNA samples from two pediatric neuroblastoma patients and found common mutations that researchers believe are responsible for the secondary leukemia. It is unknown whether the researchers screened any DNA samples from other patients treated with chemotherapy for neuroblastoma but without leukemia developed. If the mutation is common, but leukemia is not as common, then further figure out what causes the difference.

Simply knowing what mutations can be caused by the neuroblastoma chemotherapy does not mean you can stop the mutation. The majority if not all of chemotherapy are carcinogenic and the cancer causing effect is a chance work.

Leukemia is the first type of secondary cancers that will show up before other types of secondary cancers induced by radiation therapy and chemotherapy. This is so because bone marrow is the most sensitive tissue to the treatments and mutations are easiest in the tissue. Many cancer patients will develop secondary cancers after cancer treatments.

該研究報告肯定承認神經母細胞瘤的化學療法可引起白血病。目前尚不清楚接受化療的神經母細胞瘤患者發展為繼發性白血病需要多長時間。

這項研究篩選了兩名小兒神經母細胞瘤患者的DNA樣本,發現了研究人員認為導致繼發性白血病的常見突變。尚不清楚研究人員是否從其他接受過化學療法治療的神經母細胞瘤患者中篩選出任何DNA樣本,但未發現白血病。如果突變是常見的,但白血病並不常見,則進一步找出導致差異的原因。

僅僅知道神經母細胞瘤化療會導致哪些突變並不意味著您可以停止該突變。大多數化學療法(如果不是全部的話)都是致癌的,而致癌作用是偶然的。

白血病是繼發於放射療法和化學療法誘發的其他類型的繼發性癌症之後出現的第一類型的繼發性癌症。之所以如此,是因為骨髓是對治療最敏感的組織,而組織中的突變最容易發生。許多癌症患者在接受癌症治療後會發展為繼發性癌症。

News Release 28-May-2021

New study used whole genome sequencing to gain further understanding of why some children develop secondary leukaemia after neuroblastoma treatment

Wellcome Trust Sanger Institute

Research News

Scientists from the Wellcome Sanger Institute and the University of Cambridge found that in children with neuroblastoma – a cancer of immature nerve cells – treatment with platinum chemotherapy caused changes to the genome that could then cause leukaemia in some children later on.

The findings, published 27th May 2021 in Blood could lead to an ability to identify which children are more likely to develop the secondary cancer. This in turn could lead to changes in their treatment plan to either avoid these risks or take measures to prepare.

Secondary blood cancer is a challenging complication of childhood neuroblastoma cancer treatment. Every year around 100 children in the UK are diagnosed with neuroblastoma*, and those who had high-risk treatment are at an increased risk of developing secondary blood cancer – leukaemia – after neuroblastoma treatment.

Neuroblastoma often requires intense treatment including several chemotherapy drugs. These powerful drugs kill cancer cells very effectively but unfortunately also have side effects, including damaging the DNA of healthy cells, including bone marrow cells. In up to 7 per cent of childhood neuroblastoma survivors, damaged bone marrow cells go on to develop into secondary leukaemia.

In this new study, researchers from the Wellcome Sanger Institute and the University of Cambridge sequenced the whole genomes of bone marrow and blood samples of two children who both had developed blood cancer following high-risk neuroblastoma treatment. They discovered that the seeds of secondary leukaemia were sown by neuroblastoma chemotherapy right at the beginning of treatment.

Dr Sam Behjati, co-lead author and group leader at the Wellcome Sanger Institute, said: “We have been able to unravel the root of secondary leukaemia in these children which seems to lie in the early stages of neuroblastoma treatment. We hope to further investigate this to try to identify children at higher risk, and to inform a more tailored treatment plan to reduce the risk of secondary leukaemia.”

The team found that in both patients the leukaemia had mutations that were caused by neuroblastoma chemotherapy. A wider analysis of 17 children treated for a variety of cancers then identified another child who had undergone neuroblastoma treatment and had developed pre-leukaemia seeds. In the future, it could be possible to identify the children who have a higher risk of developing secondary leukaemia by sequencing their genome and highlighting any genetic drivers that could be pre-cursors for blood cancer.

Dr Grace Collord, joint first author from the Wellcome Sanger Institute, said: “This research would not have been possible without the contributions of the patients and their families, and we are indebted to them for their participation in this study. Understanding the reason why some childhood cancer survivors go on to develop secondary blood cancer is crucial if we are to find a way to help protect against this devastating complication.”

Professor John Anderson of Great Ormond Street Hospital, who contributed to this study, said: “Neuroblastoma can be an aggressive disease that requires intense chemotherapy treatment. Occasionally this chemotherapy can cause serious adverse effects such as leukaemia. So these findings are important to inform possible strategies for monitoring for secondary cancer and tailoring individual treatment plans. However, I should stress that it remains vital that children with high risk neuroblastoma continue to receive intense treatment for their cancer.”

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This study included patients, research nursing teams, and laboratory staff from Addenbrooke’s Cambridge University Hospital and Great Ormond Street Hospital (London).

*Children with Cancer UK. Neuroblastoma overview, accessed 02/03/2021. Available at: https://www.childrenwithcancer.org.uk/childhood-cancer-info/cancer-types/neuroblastoma/#:~:text=are%20not%20known.-,Incidence,the%20age%20of%2010%20years.

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