[Myeloproliferative neoplasm with a homozygous germline SH2B3 mutation: a case report and literature review].

Abstract

This study retrospectively analyzed the clinical data of the first reported case in China of myeloproliferative neoplasm (MPN) driven by a homozygous germline SH2B3 mutation, aiming to deepen the understanding of this rare MPN subtype. The patient was a 59-year-old female admitted due to intermittent fatigue and fever for 3 years, which had worsened 4 days prior to admission. Next-generation sequencing revealed a homozygous germline SH2B3 gene mutation (c.1481C>A, p.S494*) with a variant allele frequency (VAF) of 100%. Family analysis confirmed its germline origin, and her children were all heterozygous carriers of the SH2B3 mutation with normal phenotypes. Based on hematological examination and bone marrow pathology, MPN was definitively diagnosed. The main clinical manifestations included fever, night sweats, elevated WBC and PLT, and splenomegaly. As a negative regulator of JAK2, inactivating mutations in the SH2B3 gene lead to weakened negative regulation of the JAK2/STAT signaling pathway by the SH2B3 protein, thereby causing continuous activation of this pathway and inducing the development of MPN. After treatment with the JAK1/JAK2 inhibitor ruxolitinib 20 mg twice daily, the patient's body temperature returned to normal, fatigue and night sweats resolved, and spleen size decreased, demonstrating significant therapeutic efficacy.