Outgrowth of a CSF3R-mutant clone drives a second myeloproliferative neoplasm in a chronic myeloid leukemia patient: a case report
Year: 2021
Type: article
Study design: Case Report
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.
Source: Biomarker Research
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,890
Funders: Howard Hughes Medical Institute, American Cancer Society, American Society of Hematology, Gilead Sciences, European Hematology Association, Gilead Foundation, Gilead Research Scholars, National Institutes of Health, National Cancer Institute, National Center for Advancing Translational Sciences
Awards: Characterizing the landscape of resistance and persistence mechanisms in CML, Determining the biological importance of SETBP1 functional domains to develop novel therapeutic approaches for myeloid leukemias, Functional Genomic Discovery of Pathway Targeted and Immune Modulatory Therapeutic Combinations in Hematologic Malignancies, Targeting oncogene interaction in acute myeloid leukemia, Epigenetics of Mutation-Order in Acute Myeloid Leukemia, G6623253635, Architecture and Trajectory of Acquired Resistance to Therapy in AML, Institutional Career Development Core
OpenAlex ID: W3126633361