Genetic Testing Identifies Inherited Predisposition in Children With Acute Leukemia

Previous studies estimate that 4% to 10% of children with hematological malignancies carry a germline cancer predisposition, although reported rates vary by study design and patient selection. Detecting these variants can be difficult when there is no prior indication of hereditary cancer risk. To improve identification in these cases, new findings show that genetic testing can help uncover germline predisposition underlying childhood leukemia.

Researchers at Karolinska Institutet (Stockholm, Sweden) evaluated germline predisposition in children with newly diagnosed acute leukemia in Sweden. The study used clinical assessment of symptoms and family history, whole-genome sequencing to analyze the entire genome, and genetic analysis of tumor tissue. The findings were published in Nature Communications on September 29, 2026.

The nationwide prospective cohort included 181 children who had recently received an acute leukemia diagnosis. Overall, 9 of the 181 children, or approximately 5%, carried genetic variants indicating a germline predisposition to leukemia. Six children had genetic aberrations specifically associated with leukemia, while three carried rare variants in genes previously linked to solid tumors.

In 6 of the 9 children, increased cancer risk had not been recognized before the leukemia diagnosis. After the variants were identified, eight children were enrolled in specialized surveillance programs, and four had treatment modifications. The researchers noted that the proportion identified in this study was somewhat lower than in earlier estimates, partly because all children were included regardless of any prior suspicion of hereditary cancer risk.

The study was carried out in collaboration between six Swedish university hospitals and research groups within Genomic Medicine Sweden. The researchers also noted a study limitation, as analyses focused on a predefined list of genes and may have missed some genetic causes. They stated that larger studies are needed to better understand the contribution of germline genetic factors to childhood leukemia.

 “Our results show that genetic testing can provide clinically important information that influences both treatment and follow-up. At the same time, the benefits need to be weighed against available resources and the need for genetic counseling,” says Bianca Tesi, consultant clinical geneticist at the Department of Clinical Genetics and Genomics, Karolinska University Hospital, and co-senior author of the study.

 “By sequencing every child and combining comprehensive clinical evaluation with whole-genome sequencing and tumor analysis, we obtained a complete picture of how common germline variants are and which genes are involved,” added Fulya Taylan, associate professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and the first author of the study.

Related Links
Karolinska Institutet