title: Durable Disease Control with MEK Inhibition in a Patient with NRAS-mutated Atypical Chronic Myeloid Leukemia.
abstract: Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are rare hematologic neoplasms characterized by leukocytosis and a hypercellular bone marrow. Although recurrent mutations in the colony-stimulating factor 3 receptor (CSF3R) are frequently observed in patients with (CNL), the mutational landscape in (aCML) is less well-defined. In this report, we describe an 81-year-old male who was diagnosed with aCML. He presented with leukocytosis and anemia but no significant clinical symptoms. Standard laboratory studies revealed the absence of the Philadelphia chromosome. Massively parallel sequencing demonstrated no mutations in CSF3R, but the presence of a heterozygous NRAS-G12D variant (47% allele frequency). The patient was started on treatment with trametinib, an MEK1/2 inhibitor with Food and Drug Administration approval for malignant melanoma. Therapy with trametinib resulted in exceptional improvements in his blood counts and continued disease control with 14 months of follow-up. This case highlights the need for clinical trials evaluating the safety and efficacy of MEK1/2 as a therapeutic target for the treatment of patients with NRAS-mutated aCML/CNL.
authors: Knight Cancer Institute, Oregon Health & Science University ; Howard Hughes Medical Institute Medical Research Fellows Program, Howard Hughes Medical Institute ; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University.
authors: Vishesh
authors: V
authors: Khanna
authors: Department of Hematology/Oncology, Saint Joseph Hospital.
authors: Scott T
authors: ST
authors: Pierce
authors: Knight Cancer Institute, Oregon Health & Science University.
authors: Kim-Hien T
authors: KH
authors: Dao
authors: Knight Cancer Institute, Oregon Health & Science University.
authors: Cristina E
authors: CE
authors: Tognon
authors: Saint Joseph Hospital Laboratory, Saint Joseph Hospital.
authors: David E
authors: DE
authors: Hunt
authors: Knight Cancer Institute, Oregon Health & Science University.
authors: Brian
authors: B
authors: Junio
authors: Knight Cancer Institute, Oregon Health & Science University.
authors: Jeffrey W
authors: JW
authors: Tyner
authors: Knight Cancer Institute, Oregon Health & Science University ; Howard Hughes Medical Institute Investigator Program, Howard Hughes Medical Institute ; Division of Hematology & Medical Oncology, Oregon Health & Science University ; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University.
authors: Brian J
authors: BJ
authors: Druker
keywords: atypical chronic myeloid leukemia; chronic neutrophilic leukemia; nras; trametinib