title: Integration of ruxolitinib into dose-intensified therapy targeted against a novel JAK2 F694L mutation in B-precursor acute lymphoblastic leukemia.
abstract: A 17-year-old girl with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with persistent minimal residual disease (MRD) who underwent standard chemotherapy was found to have a BCR-ABL1-like gene expression pattern. Genome sequencing revealed a JAK2 mutation not previously described in BCP-ALL and a potential therapeutic target. Due to concern for an on-therapy relapse, the JAK2 inhibitor ruxolitinib was incorporated into a modified chemotherapy backbone to achieve complete remission prior to stem cell transplant. Treatment was well tolerated and she had undetectable MRD prior to a matched allogeneic stem cell transplant and remained in remission at day +100.
authors.affiliation: Department of Pediatrics, Hematology Oncology, University of New Mexico, New Mexico, Albuquerque.
authors.forename: Jodi R
authors.initials: JR
authors.lastname: Mayfield
authors.affiliation: Department of Pathology, University of New Mexico, New Mexico, Albuquerque.
authors.forename: David R
authors.initials: DR
authors.lastname: Czuchlewski
authors.affiliation: Department of Pathology, TriCore Reference Laboratories, Albuquerque, New Mexico.
authors.forename: James M
authors.initials: JM
authors.lastname: Gale
authors.affiliation: Department of Pediatrics, Hematology Oncology, University of New Mexico, New Mexico, Albuquerque.
authors.forename: Ksenia
authors.initials: K
authors.lastname: Matlawska-Wasowska
authors.affiliation: Department of Pathology, University of New Mexico, New Mexico, Albuquerque.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Vasef
authors.affiliation: Department of Pediatrics, Hematology Oncology, University of New Mexico, New Mexico, Albuquerque.
authors.forename: Christian
authors.initials: C
authors.lastname: Nickl
authors.affiliation: Analytical and Translational Genomics Shared Resource, UNM Comprehensive Cancer Center, University of New Mexico, New Mexico, Albuquerque.
authors.forename: Gavin
authors.initials: G
authors.lastname: Pickett
authors.affiliation: Department of Internal Medicine, Division of Molecular Medicine and UNM Comprehensive Cancer Center, University of New Mexico, New Mexico, Albuquerque.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Ness
authors.affiliation: Department of Pediatrics, Hematology Oncology, University of New Mexico, New Mexico, Albuquerque.
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Winter
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation / Q000235:genetics; D018365:Neoplasm, Residual / Q000188:drug therapy; D009570:Nitriles; D057285:Precision Medicine / Q000379:methods*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
chemical_list: C581634:BCR-ABL1 fusion protein, human; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D016044:Fusion Proteins, bcr-abl; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: TKI; personalized medicine; targeted therapy; tyrosine kinase inhibitor; variant of unknown significance