@article{5abe393a0af14988a28ce318066c2358,
title = "Outgrowth of a CSF3R-mutant clone drives a second myeloproliferative neoplasm in a chronic myeloid leukemia patient: a 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{\textquoteright}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.",
keywords = "Case report, Chronic myeloid leukemia, Chronic neutrophilic leukemia, Clonal evolution, Myeloproliferative neoplasm, Tyrosine kinase inhibitors",
author = "Carratt, {Sarah A.} and Diana Brewer and Maxson, {Julia E.} and Druker, {Brian J.} and Braun, {Theodore P.}",
note = "Funding Information: SAC is supported by a fellowship from the National Cancer Institute, F32CA239422. JEM is supported by an American Society of Hematology Scholar Award, a Gilead Research Scholars Award, and American Cancer Society RSG-19-184-01-LIB. TPB is supported by KL2 TR002370–03 and K08 CA245224–01. BJD is supported by Howard Hughes Medical Institute and R01 CA065823–24. Funding Information: B.J.D. potential competing interests–SAB: Aileron Therapeutics, ALLCRON, Cepheid, Vivid Biosciences, Celgene, RUNX1 Research Program, EnLiven Therapeutics, Gilead Sciences (inactive), Baxalta (inactive), Monojul (inactive); SAB and stock: Aptose Biosciences, Blueprint Medicines, Beta Cat, Third Coast Therapeutics, GRAIL (inactive), CTI BioPharma (inactive); scientific founder: MolecularMD (inactive, acquired by ICON); board of directors and stock: Amgen; board of directors: Burroughs Wellcome Fund, CureOne; joint steering committee: Beat AML LLS; founder: VP Therapeutics; clinical trial funding: Novartis, Bristol-Myers Squibb, Pfizer; royalties from Patent 6958335 (Novartis exclusive license) and OHSU and Dana- Farber Cancer Institute (one Merck exclusive license). B.J.D. potential competing interests– consultant: Monojul, Patient True Talk; SAB: Aileron Therapeutics, ALLCRON, Cepheid, Gilead Sciences, Vivid Biosciences, Celgene & Baxalta (inactive); SAB and stock: Aptose Biosciences, Blueprint Medicines, Beta Cat, GRAIL, Third Coast Therapeutics, CTI Bio-Pharma (inactive); scientific founder and stock: MolecularMD; board of directors and stock: Amgen; board of directors: Burroughs Wellcome Fund, CureOne; joint steering committee: Beat AML LLS; clinical trial funding: Novartis, Bristol-Myers Squibb, Pfizer; royalties: OHSU #606-Novartis exclusive license, OHSU #2573; Dana-Farber Cancer Institute #2063- Merck exclusive license. J.E.M. receives grant funding from the Gilead Research Scholars Program. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = dec,
doi = "10.1186/s40364-021-00261-4",
language = "English (US)",
volume = "9",
journal = "Biomarker Research",
issn = "2050-7771",
publisher = "BioMed Central Ltd.",
number = "1",
}