Detecting Multiple Driver Mutations in a Patient with Essential Thrombocythemia.

ABSTRACT

BACKGROUND Three driver mutations have been identified in patients with essential thrombocythemia - JAK2 V617F, CALR, and MPL. Out of these, JAK2 V617F is mostly common. These mutations are thought to be mutually exclusive; therefore, the initial workup may not include the identification of all mutations separately. CASE REPORT We present a case of a 55-year-old woman who was referred to the hematology clinic for an elevated platelet count noted when she was hospitalized for a renal stone. The patient was asymptomatic. A workup was initiated for essential thrombocythemia, and she was tested for JAK2 V617F mutation using an allele-specific polymerase chain reaction (AS-PCR) test in peripheral blood, which came back positive. The variant allele frequency was 2%. She underwent a bone marrow biopsy, and next-generation sequencing (NGS) showed a CALR mutation. A 52 bp deletion-type mutation was detected in the CALR gene on exon 9, with a variant allele frequency of 7%. The NGS did not detect JAK2 mutation due to its low sensitivity. She was started on aspirin alone as she was less than 60 years old and had no history of thrombotic events. The patient has been following up with the hematology clinic for the last 2 years and has not had any thrombotic events. CONCLUSIONS We propose that in patients with a low JAK2 V617 allele variant, testing for other driver mutations should be performed. In our patient, JAK2 mutation could be clonal hematopoiesis of indeterminate potential; therefore, the dominant mutation (CALR) would determine the disease phenotype.