Abstract Casitas B‐cell lineage (CBL) syndrome is a rare RASopathy known to predispose to CBL‐mutated juvenile myelomonocytic leukemia (JMML) in childhood. Adulthood acute myeloid leukemia arising out of a genetic aberrancies consistent with prior CBL‐mutated JMML has been twice previously described, but chronic myeloproliferative neoplasia has not. We present a case of progressive myeloproliferative neoplasm in adulthood in the context of CBL syndrome alongside a novel CSF3R variant. We also review pathogenic splice‐site mutations in CBL‐mutated JMML.
