Efficacy of ruxolitinib in a patient with myelodysplastic/myeloproliferative neoplasm unclassifiable and co-mutated JAK2, SF3B1 and TP53

Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) is a rare but heterogeneous subtype of MDS/MPN, with no specific genetic alterations and standard treatments. ASXL1, SRSF2, TET2, JAK2 and NRAS are commonly mutated in MDS/MPN-U. Double gene mutations could be detected in MDS/MPN-U, however, co-mutations of 3 and more genes in this disease entity are very rare. Here, we present a case of MDS/MPN-U with triple mutations involving JAK2, SF3B1, and TP53. After failure of traditional therapy including hydroxyurea and interferon-α, the patient received ruxolitinib monotherapy and achieved hematological response quickly. Though mutations in TP53 implied a poor prognosis in myeloid malignancies, this patient has maintained no AML transformation for 26 months since diagnosis. Further research on complex mutations in the pathogenesis and prognosis of MDS/MPN-U is warranted.