Atypical Chronic Myeloid Leukemia in Two Pediatric Patients

Pediatr Blood Cancer. 2016 Jan;63(1):156-9. doi: 10.1002/pbc.25694. Epub 2015 Aug 14.


Atypical chronic myeloid leukemia, BCR-ABL1-negative, (aCML) is a rare myeloid neoplasm. Recent adult data suggest the leukemic cells in a subset of patients are dependent on JAK/STAT signaling and harbor CSF3R-activating mutations. We hypothesized that, similar to adult patients, the presence of CSF3R-activating mutations would be clinically relevant in pediatric myeloid neoplasms as patients would be sensitive to the JAK inhibitor, ruxolitinib. We report two cases of morphologically similar pediatric aCML, BCR-ABL1-negative based on WHO 2008 criteria. One patient had CSF3R-activating mutation (T618I) and demonstrated a robust response to ruxolitinib, which was used to bridge to a successful stem cell transplant. The other patient did not have a CSF3R-activating mutation and succumbed to refractory disease <6 months from diagnosis. This report documents CSF3R-T618I in pediatric aCML and demonstrates the efficacy of ruxolitinib in a pediatric malignancy. As the third documented case successfully treating aCML with ruxolitinib, this case highlights the importance of prompt CSF3R sequencing analysis for myeloproliferative and myelodysplastic/myeloproliferative neoplasms.

Keywords: BCR-ABL1 negative; atypical CML; leukemia; myeloid; pediatrics.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Child
  • Female
  • Humans
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / drug therapy*
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / genetics*
  • Mutation
  • Nitriles
  • Pyrazoles / therapeutic use*
  • Pyrimidines
  • Receptors, Colony-Stimulating Factor / genetics*


  • CSF3R protein, human
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • Receptors, Colony-Stimulating Factor
  • ruxolitinib