Involvement of the JAK-STAT Pathway in the Molecular Landscape of Fusion-Free Myeloid Neoplasms with Eosinophilia

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.78-78
• Main Authors: Groh, Matthieu, Fenwarth, Laurène, Boudry, Augustin, Fournier, Elise, Marceau-Renaut, Alice, Abraham, Julie, Barry, Marly, Blanche, Philippe, Bodard, Quentin, Braun, Thorsten, Chebrek, Safia, Daltro De Oliveira, Rafael, Decamp, Matthieu, Durel, Cécile Audrey, Forcade, Edouard, Gerfaud-Valentin, Mathieu, Golfier, Camille, Gourguechon, Clement, Grardel, Nathalie, Kosmider, Olivier, Labro, Mathilde, Melboucy Belkhir, Sarah, Merabet, Fatiha, Michon, Adrien, Martis, Nihal, Morice, Cécile, Moreau, Stephane, Néel, Antoine, Nicolini, Franck E., Pascal, Laurent, Pasquier, Florence, Pieragostini, Andrea, Roche-Lestienne, Catherine, Rousselot, Philippe, Thiebaut, Anne, Viallard, Jean-Francois, Wemeau, Mathieu, Preudhomme, Claude, Kahn, Jean-Emmanuel, Lefèvre, Guillaume, Duployez, Nicolas
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-181250

Introduction. Gene fusions leading to the constitutive activation of tyrosine kinases (TK) such as PDGFRA, PDGFRB or FGFR1 have been the first recurrent genetic defects involved in myeloid hypereosinophilic syndromes (HES). Although activation of the Janus kinase (JAK)/Signal Transducer and Activator of Transcription(STAT) pathway is critical for eosinophil production and survival, genes involved in the JAK/STAT pathway are not included in most next-generation sequencing (NGS) panels used for the etiological workup of hypereosinophilia (HE). Methods. A custom 149-gene NGS panel including subunits of the IL3/IL5/GM-CSF receptors, TK ( PDGFRA/B, FGFR1, ABL1, FLT3, KIT), intracellular proteins of the JAK-STAT and RAS-MAPK pathways was performed in 64 consecutive adult patients (experimental group) referred between March 2012 to June 2023 to the French Reference Center for Hypereosinophilic Syndromes (CEREO) for HE/HES displaying at least one clinic-biological feature suggestive of myeloid neoplasm ( i.e. splenomegaly, other unexplained CBC abnormality besides HE, increased serum tryptase and/or vitamin B12 levels, corticosteroid-refractory HE and/or sensitivity to either TK inhibitors or JAK inhibitors). All of them were negative by PCR and/or FISH analyses for gene rearrangements involving PDGFRA, PDGFRB or FGFR1. Patients with lymphocytic HES (n=7), idiopathic HES (n=26) and HE of undetermined significance (n=11) were used as controls (total, n=44). Results. Concordant with the latest recommendations of the international cooperative working group on eosinophil-associated disorders, at least one mutation was reported in 50/64 (78%) patients of the experimental group versus 8/44 (18%) patients in the control group (p