Outgrowth of a CSF3R-mutant clone drives a second myeloproliferative neoplasm in a chronic myeloid leukemia patient: a case report

Sarah A. Carratt, Diana Brewer, Julia E. Maxson, Brian J. Druker, Theodore P. Braun

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Chronic myeloid leukemia (CML) and chronic neutrophilic leukemia (CNL) are two myeloproliferative neoplasms with mutually exclusive diagnostic criteria. A hallmark of CML is the Philadelphia chromosome (Ph), which results in a BCR-ABL1 fusion gene and constitutive tyrosine kinase activity. CNL is a Ph-negative neoplasm and is defined in part by the presence of CSF3R mutations, which drive constative JAK/STAT signaling. Case presentation: Here, we report the exceedingly rare co-occurrence of two granulocytic myeloproliferative neoplasms in a 69-year old male patient. After an initial diagnosis of chronic myeloid leukemia, the patient’s clinical course was shaped by hematologic toxicity, the emergence of treatment-resistant BCR-ABL1 clones, and the expansion of a CSF3R-mutant clone without ABL1 mutations under selective pressure from tyrosine kinase inhibitors. The emergence of the CSF3R-mutant, neutrophilic clone led to the diagnosis of CNL as a second myeloproliferative neoplasm in the same patient. Conclusions: This is the first reported case of CNL arising subsequent to CML, which occurred under selective pressure from targeted therapy in a patient with complex clonal architecture. Patients with such molecularly complex disease may ultimately benefit from combination therapy that targets multiple oncogenic pathways.

Original languageEnglish (US)
Article number8
JournalBiomarker Research
Volume9
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Case report
  • Chronic myeloid leukemia
  • Chronic neutrophilic leukemia
  • Clonal evolution
  • Myeloproliferative neoplasm
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint Dive into the research topics of 'Outgrowth of a CSF3R-mutant clone drives a second myeloproliferative neoplasm in a chronic myeloid leukemia patient: a case report'. Together they form a unique fingerprint.

Cite this