Rare occurrence of the JAK1 mutation in acute promyelocytic leukemia patients

摘要

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a chromosome translocation of t(15;17)(q24;q21) which involves fusion of the retinoic acid receptor a (RARa) gene in chromosome 17 and the promyelocytic leukemia (PML) gene in chromosome 15. The fusion protein encoded by the PML/ RARa gene makes APL sensitive to a[-trans retinoic acid, a derivative of vitamin A. With the introduction of all-frans retinoic acid and arsenic trioxide in the past several decades, the complete remission (CR) rate and 5:year disease-free survival for APL were elevated to more than 90% [1].The Janus kinase (JAK) is a nonreceptor tyrosine ki-nase, including 4 family members, i.e. JAK1, JAK2, JAK3, and TYK2. The JAK1 gene is organized into 25 exons, including 24 coding exons, and spans about 133.28 Kb in the chromosome Ip31.3 region, which is responsible for transducing cytokine-induced signals via JAK-STAT pathway aberrations; JAK1 signal activation is partially responsible for leukemogenesis. Recently, Wartman et al. [2] found Jakl (V657F) in a murine APL model via whole genomic sequencing. This Jakl (V657F) was identified in 6 other mice that were not closely related to the proband [2]. After analyzing 186 acute adulthood leukemias, 30 multiple myelomas, and 278 common solid cancers, Jeong et al. [3] discovered 4 JAK1 mutations in patients with acute leukemia. Among them, the JAK1 mutations V658F and L783F occurred in 4 leukemia patients, while the p.V658F mutation was found in 1 patient with APL [3]. In our previous report, the JAK1 mutation was found in 3 out of 49 in acute T-lymphocytic leukemia patients [4]. To explore the frequency of the JAK1 mutation in APL, we performed JAK1 gene sequencing in a group of APL patients in our center. This study was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University. Informed consent was provided following the Declaration of Helsinki.