Publication: A novel activating JAK1 mutation in chronic eosinophilic leukemia
Issued Date
2021-09-28
Resource Type
ISSN
24739537
24739529
24739529
Other identifier(s)
2-s2.0-85116103325
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Mahidol University
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SCOPUS
Bibliographic Citation
Blood Advances. Vol.5, No.18 (2021), 3581-3586
Suggested Citation
William Shomali, Alisa Damnernsawad, Talent Theparee, David Sampson, Quinlan Morrow, Fei Yang, Sebastian Fernandez-Pol, Richard Press, James Zehnder, Jeffrey W. Tyner, Jason Gotlib A novel activating JAK1 mutation in chronic eosinophilic leukemia. Blood Advances. Vol.5, No.18 (2021), 3581-3586. doi:10.1182/bloodadvances.2021004237 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/77843
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Title
A novel activating JAK1 mutation in chronic eosinophilic leukemia
Abstract
Hypereosinophilia (HE) has been defined as persistent eosinophilia .1.5 3 109/L; it is broadly divided into primary HE (clonal or neoplastic; HEN), secondary/reactive HE (HER), or HE of undetermined significance (HEUS) when no cause is identified. The use of myeloid next-generation sequencing (NGS) panels has led to the detection of several mutations in patients previously diagnosed with HEUS, reassigning some patients to the category of HEN, specifically the World Health Organization category of chronic eosinophilic leukemia, not otherwise specified (CEL, NOS). Here, we describe a novel somatic JAK1 pseudokinase domain mutation (R629_S632delinsSA) in a patient with HE that had initially been characterized as a variant of uncertain significance. We performed functional studies that demonstrated that this mutation results in growth factor independence of Ba/F3 cells in vitro and activation of the JAK-STAT pathway. These effects were abrogated by the JAK1/ JAK2 inhibitor ruxolitinib. R629_S632delinsSA is the first known somatic mutation in JAK1 linked to a clonal eosinophilic neoplasm, and highlights the importance of the JAK-STAT pathway in eosinophil survival.
