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Updated: Dec 11, 2025

Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
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NUP98-NSD1 Driven MDS/MPN in Childhood Masquerading as JMML

Astrid Behnert1,2, Alex G Lee1,2, Elizabeth P Young1

  • 1Department of Pediatrics, Benioff Children's Hospital.

Journal of Pediatric Hematology/Oncology
|August 21, 2020
PubMed

Insights

Juvenile myelomonocytic leukemia (MDS/MPN) in children is typically driven by Ras pathway gene mutations. This study identifies a NUP98-NSD1 fusion, previously seen only in acute myeloid leukemia, as a cause of MDS/MPN in a pediatric patient.

Area of Science:

  • Hematology
  • Oncology
  • Genetics

Background:

  • Overlapping myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are rare clonal hematopoietic disorders.
  • Juvenile myelomonocytic leukemia (JMML) is the primary MDS/MPN subtype in children, characterized by Ras/MAPK pathway hyperactivation.
  • Mutations in Ras pathway genes are found in over 90% of JMML cases, with receptor tyrosine kinase translocations being rare.

Observation:

  • A 2-year-old patient presented with clinical and laboratory features of MDS/MPN.
  • Genetic analysis revealed a cytogenetically cryptic NUP98-NSD1 fusion in the patient's hematopoietic cells.

Findings:

  • The NUP98-NSD1 fusion, typically associated with acute myeloid leukemia (AML), was identified as the driver mutation in this pediatric MDS/MPN case.
  • This finding expands the known molecular landscape of pediatric MDS/MPN beyond Ras pathway mutations.

Implications:

  • The identification of NUP98-NSD1 in pediatric MDS/MPN suggests a potential new therapeutic target for this aggressive disease.
  • This case highlights the importance of comprehensive genetic screening in pediatric myeloid neoplasms, even in the presence of common JMML mutations.
  • Understanding novel genetic drivers like NUP98-NSD1 is crucial for accurate diagnosis and the development of targeted therapies in pediatric hematologic malignancies.

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