BACKGROUND: Canonical Janus kinase 2 (JAK2) V617F and exon 12 mutations in myeloid neoplasms are well described. There are limited reports of other JAK2 variants of potential clinical relevance. This study was designed to survey JAK2 variants in patients with myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML) and to determine their contributions to disease pathogenesis. METHODS: Next-generation sequencing of the coding region of JAK2 and 27 other genes was performed on bone marrow DNA samples. The study population was classified into 3 cohorts: chronic MPNs only (the MPN cohort); MPNs transformed into AML (the MPN>>AML cohort); and AML only, with MPN>>AML patients excluded (the AML cohort). RESULTS: Testing was performed for 2154 patients, and non-V617F/non-exon 12 JAK2 sequence variants were identified in 114 (5.3%). They included 35 unique JAK2 variants across all functional domains. Sixteen of the 114 JAK2 variants occurred without somatic mutations in the remaining 27 genes. JAK2 variants were detected at a higher frequency in the MPN>>AML cohort (15.3%) in comparison with the MPN (4.6%; P < .001) and AML cohorts (5.2%; P < .001). Detected variants occurred at higher than expected frequencies in patients with MPNs and AML in comparison with the population, and N1108S had a significantly increased prevalence in patients with AML. A JAK2 variant in addition to JAK2 V617F (n = 13) in myelofibrosis was associated with an increased cumulative risk of transformation into AML (P = .003). CONCLUSIONS: Specific JAK2 variants detected in MPNs may be predictors for transformation into AML.
BACKGROUND: Canonical Janus kinase 2 (JAK2) V617F and exon 12 mutations in myeloid neoplasms are well described. There are limited reports of other JAK2 variants of potential clinical relevance. This study was designed to survey JAK2 variants in patients with myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML) and to determine their contributions to disease pathogenesis. METHODS: Next-generation sequencing of the coding region of JAK2 and 27 other genes was performed on bone marrow DNA samples. The study population was classified into 3 cohorts: chronic MPNs only (the MPN cohort); MPNs transformed into AML (the MPN>>AML cohort); and AML only, with MPN>>AMLpatients excluded (the AML cohort). RESULTS: Testing was performed for 2154 patients, and non-V617F/non-exon 12 JAK2 sequence variants were identified in 114 (5.3%). They included 35 unique JAK2 variants across all functional domains. Sixteen of the 114 JAK2 variants occurred without somatic mutations in the remaining 27 genes. JAK2 variants were detected at a higher frequency in the MPN>>AML cohort (15.3%) in comparison with the MPN (4.6%; P < .001) and AML cohorts (5.2%; P < .001). Detected variants occurred at higher than expected frequencies in patients with MPNs and AML in comparison with the population, and N1108S had a significantly increased prevalence in patients with AML. A JAK2 variant in addition to JAK2 V617F (n = 13) in myelofibrosis was associated with an increased cumulative risk of transformation into AML (P = .003). CONCLUSIONS: Specific JAK2 variants detected in MPNs may be predictors for transformation into AML.
Authors: Ami B Patel; Anca Franzini; Emilie Leroy; Soo Jin Kim; Anthony D Pomicter; Lidvine Genet; Michael Xiao; Dongqing Yan; Jonathan M Ahmann; Archana M Agarwal; Phillip Clair; Juanah Addada; Jonathan Lambert; Matthew Salmon; Gerald J Gleich; Nicholas C P Cross; Stefan N Constantinescu; Thomas O'Hare; Josef T Prchal; Michael W Deininger Journal: Blood Date: 2019-12-26 Impact factor: 25.476
Authors: Ning-Yuan Lee; Melissa Hum; Pei-Yi Ong; Matthew Khine Myint; Enya H W Ong; Kar-Perng Low; Zheng Li; Boon-Cher Goh; Joshua K Tay; Kwok-Seng Loh; Melvin L K Chua; Soo-Chin Lee; Chiea-Chuen Khor; Ann S G Lee Journal: Cancers (Basel) Date: 2022-07-28 Impact factor: 6.575
Authors: Ibrahim Taha; Selena Foroni; Roberto Valli; Annalisa Frattini; Pamela Roccia; Giovanni Porta; Marco Zecca; Elena Bergami; Marco Cipolli; Francesco Pasquali; Cesare Danesino; Claudia Scotti; Antonella Minelli Journal: Front Genet Date: 2022-08-12 Impact factor: 4.772