Incorporation of somatic panels for the detection of haematopoietic transformation in children and young adults with leukaemia predisposition syndromes and with acquired cytopenias

Sharon Noy-Lotan, Tanya Krasnov, Orly Dgany, Marta Jeison, Asaf D. Yanir, Oded Gilad, Helen Toledano, Shlomit Barzilai-Birenboim, Joanne Yacobovich, Shai Izraeli, Hannah Tamary, Orna Steinberg-Shemer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Detection of somatic mutations may help verify the diagnosis of myelodysplastic syndrome (MDS) in patients with persistent cytopenias or with MDS-predisposition syndromes, prior to the development of overt leukemia. However, the spectrum and consequences of acquired changes in paediatric patients have not been fully evaluated, and especially not in the context of an underlying syndrome. We incorporated a targeted next-generation-sequencing panel of 54 genes for the detection of somatic mutations in paediatric and young adult patients with inherited or acquired cytopenias. Sixty-five patients were included in this study, of whom 17 (26%) had somatic mutations. We detected somatic mutations in 20% of individuals with inherited MDS-predisposition syndromes, including in patients with severe congenital neutropenia and Fanconi anaemia, and with germline mutations in SAMD9L. Thirty-eight per cent of children with acquired cytopenias and suspected MDS had somatic changes, most commonly in genes related to signal transduction and transcription. Molecularly abnormal clones often preceded cytogenetic changes. Thus, routine performance of somatic panels can establish the diagnosis of MDS and determine the optimal timing of haematopoietic stem cell transplantation, prior to the development of leukaemia. In addition, performing somatic panels in patients with inherited MDS-predisposition syndromes may reveal their unique spectrum of acquired mutations.

Original languageEnglish
Pages (from-to)570-580
Number of pages11
JournalBritish Journal of Haematology
Volume193
Issue number3
DOIs
StatePublished - May 2021

Funding

FundersFunder number
European Haematology Association
Israeli Center for Better Childhood
European Hematology Association

    Keywords

    • acute myeloid leukaemia
    • bone marrow failure
    • myelodysplastic syndromes
    • next generation sequencing
    • paediatric

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