A novel activating JAK1 mutation in chronic eosinophilic leukemia

William Shomali, Alisa Damnernsawad, Talent Theparee, David Sampson, Quinlan Morrow, Fei Yang, Sebastian Fernandez-Pol, Richard Press, James Zehnder, Jeffrey W. Tyner, Jason Gotlib

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3581-3586
Number of pages6
JournalBlood Advances
Issue number18
StatePublished - Sep 28 2021

ASJC Scopus subject areas

  • Hematology


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