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

• Main Authors: Sarah A. Carratt (Author), Diana Brewer (Author), Julia E. Maxson (Author), Brian J. Druker (Author), Theodore P. Braun (Author)
• Format: Book
• Published: BMC, 2021-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

10.1186/s40364-021-00261-4
2050-7771