J Korean Med Sci.  2020 Jun;35(23):e168. 10.3346/jkms.2020.35.e168.

A Rare Case of Essential Thrombocythemia with Coexisting JAK2 and MPL Driver Mutations

• Jang MA
• Seo MY
• Choi KJ
• Hong DS

• KMID: 2502919
• DOI: http://doi.org/10.3346/jkms.2020.35.e168

Abstract

Philadelphia-negative (Ph−) classical myeloproliferative neoplasms (MPNs) include polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis. Somatic driver mutations in the JAK2, CALR, and MPL genes serve as major diagnostic criteria of the Ph− MPNs and these mutations occur in a mutually exclusive manner. In this report, we describe the first case of ET harboring double mutations in JAK2 V617F and MPL. For MPL, the patient had multiple clones of MPL mutations: c.1543_1546delinsAGGG (p.Trp515_Gln516delinsArgGlu) and c.1546C>G (p.Gln516Glu). The JAK2 V617F allele burden in our patient is very low (4%) compared to the relatively high (17%–78%) allele frequency of MPL mutations. The low JAK2 mutant burden might be explained by preexisting clonal hematopoiesis before overt signs of MPNs, followed by the acquisition of a second oncogenic mutation of CALR or MPL leading to the MPN phenotype. This highlights that screening for a second driver mutation should be considered in patients with a low JAK2 mutant burden by reporting a 57-year-old Korean man with ET.

Keyword

Essential Thrombocythemia; Mutation; JAK2; MPL

Figure

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  Fig. 1 Hematological and molecular characteristics of an essential thrombocythemia patient with coexisting JAK2 and MPL driver mutations. (A) Peripheral blood is unremarkable, except for thrombocytosis (708 ×109/L) (Wright-Giemsa stain, ×400). (B) Bone marrow aspirate exhibits normal cellularity but increased number of large megakaryocytes with hyperlobulated nuclei (hematoxylind and eosin stain, ×400). (C) Segments of the MPL sequence electropherogram of the original PCR product, and of three TA-clones obtained from a second PCR product revealed wild-type, c.1543_1546delinsAGGG, and c.1546C>G in the mix. Note the correspondence between the variable sites (arrows) distinguishing the cloned sequences and the double peaks observed in the original sequence.PCR = polymerase chain reaction.

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