Skip to main content
 
Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
Stanford Health Care

A novel activating JAK1 mutation in chronic eosinophilic leukemia.

A novel activating JAK1 mutation in chronic eosinophilic leukemia. Blood advances Shomali, W., Damnernsawad, A., Theparee, T., Sampson, D., Morrow, Q., Yang, F., Fernandez-Pol, S., Press, R. D., Zehnder, J. L., Tyner, J. W., Gotlib, J. R. 2021

Abstract

Hypereosinophilia (HE) has been arbitrarily defined as persistent eosinophilia >1.5 x109/L, and is broadly divided into primary (clonal or neoplastic; HEN), secondary/reactive (HER), or of undetermined significance (HEUS) when no cause is identified. The use of myeloid next generation sequencing 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 been initially characterized as a variant of uncertain significance. We performed functional studies that demonstrate that this mutation results in growth factor independence of Ba/F3 cells in vitro and activation of the Janus Kinase-Signal Transducer and Activator of Transcription Proteins (JAK-STAT) pathway. These effects were abrogated by the JAK1/JAK2 inhibitor ruxolitinib. The 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.

View details for DOI 10.1182/bloodadvances.2021004237

View details for PubMedID 34496019