Presence of triple positive driver mutations in JAK2, CALR and MPL in primary myelofibrosis: a case report and literature review

Abstract

Background Primary myelofibrosis (PMF) is the most advanced subtype among the classic Philadelphia chromosomenegative myeloproliferative neoplasms (MPNs). A majority of patients carry one of three mutually-exclusive somatic driver mutations: JAK2 (60–65%), CALR (20–25%), or MPL (5%). Co-occurrence of these mutations is rarely reported. Here we report a case with a triple positive combination of JAK2, CALR and MPL driver mutations.Case presentation A 69-year-old male was admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (COPD) and was found to have splenomegaly and leukocytosis. Nextgeneration revealed JAK2, CALR, MPL mutations, and additional variants in SF3B1, SRSF2, and STAG2. The patient was diagnosed with PMF and treated with ruxolitinib and COPD therapy. Due to nausea, the ruxolitinib dose was reduced. After therapy, spleen volume decreased and hematologic responses were poor. Another genetic mutation of ASXL1 was later found. After adjusting the medication and adding antiemetics, the patient's condition improved.Conclusions The rare coexistence of JAK2, CALR, and MPL mutations challenges the assumption of their mutual exclusivity. Further study of these mutations is essential for developing better treatment strategies.

Keywords

• Driver mutations
• co-occurrence
• primary myelofibrosis