title: Significant clinical response to JAK1/2 inhibition in a patient with CSF3R-T618I-positive atypical chronic myeloid leukemia.
abstract: Mutations in CSF3R (colony-stimulating factor 3 receptor) are frequent oncogenic drivers in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). Here we describe a 75 year old man who was diagnosed with CSF3R-T618I-positive atypical CML. He presented with leukocytosis, anemia, and thrombocytopenia and developed massive splenomegaly and severe constitutional symptoms. Hydroxyurea was given over a 6 month period but failed to provide any measureable clinical benefit. Eventually, he was treated with ruxolitinib, an FDA-approved JAK1/2 inhibitor, which resulted in dramatic improvement of his blood counts. He also had significant reduction of spleen volume and constitutional symptoms. This case highlights the need for a clinical trial to interrogate JAK1/2 as a potential molecular target in CNL and aCML in patients with or without CSF3R mutation. A clinical trial evaluating the safety and efficacy of ruxolitinib for this patient population is registered at ClinicalTrials.gov (NCT02092324).
authors.affiliation: Oregon Health and Sciences University, Knight Cancer Institute, Hematology and Medical Oncology, Portland, OR, USA.
authors.forename: Kim-Hien T
authors.initials: KH
authors.lastname: Dao
authors.affiliation: Compass Oncology, Vancouver, WA, USA.
authors.forename: Magdolna B
authors.initials: MB
authors.lastname: Solti
authors.affiliation: Oregon Health and Sciences University, Knight Cancer Institute, Hematology and Medical Oncology, Portland, OR, USA.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Maxson
authors.affiliation: Emory University, Winship Cancer Institute, Atlanta, GA, USA.
authors.forename: Elliott F
authors.initials: EF
authors.lastname: Winton
authors.affiliation: Oregon Health and Sciences University, Department of Pathology, Portland, OR, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Press
authors.affiliation: Oregon Health and Sciences University, Knight Cancer Institute, Hematology and Medical Oncology, Portland, OR, USA ; Howard Hughes Medical Institute, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
authors.affiliation: Oregon Health and Sciences University, Knight Cancer Institute, Hematology and Medical Oncology, Portland, OR, USA ; Oregon Health and Sciences University, Knight Cancer Institute, Cell and Developmental Biology, Portland, OR, USA.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Tyner
keywords: Atypical chronic myeloid leukemia; Chronic neutrophilic leukemia; Colony-stimulating factor 3 receptor; Ruxolitinib