biostudies-literatureSpiciarich DRNCIEuropean Hematology AssociationNCI NIH HHSNIHNIH HHSNIGMS NIH HHS6762-6770https://www.ebi.ac.uk/biostudies/studies/S-EPMC6295230biostudies-literatureUnknown78(24): Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia. Here, we studied the function of novel germline variants in CSF3R at amino acid N610. These N610 substitutions were potently oncogenic and activated the receptor independently of its ligand GCSF. These mutations activated the JAK-STAT signaling pathway and conferred sensitivity to JAK inhibitors. Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans. N610 was also the primary site of sialylation of the receptor. Membrane-proximal N-linked glycosylation was critical forCancer researchA Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia.PMC6295230TRTH171P30 CA008748U01 CA207702R00 CA1906051S10OD020062-01U01 CA207701P41 GM103490U54 CA2240194P41GM103490-14R01 CA207701S10 OD0185301S10OD018530S10 OD020062R01 CA200423R00-CA190605R01 CA247943Oh STSpiciarich DRChen QFoley AMauro MJPress RDBertozzi CRMaxson JEHughes SBThompson SLAzadi PViner RAbdel-Wahab OfalseA Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia.: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia. Here, we studied the function of novel germline variants in CSF3R at amino acid N610. These N610 substitutions were potently oncogenic and activated the receptor independently of its ligand GCSF. These mutations activated the JAK-STAT signaling pathway and conferred sensitivity to JAK inhibitors. Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans. N610 was also the primary site of sialylation of the receptor. Membrane-proximal N-linked glycosylation was critical for2018-01-01T00:00:00Z2018 Dec2026-04-29T20:59:12.132Z2026-04-14T03:07:06.86ZS-EPMC62952303034880910.1158/0008-5472.can-18-163810.1158/0008-5472.CAN-18-1638