Co-occurrence of CALR and MPL somatic mutations in an Indian patient with a Philadelphia-negative myeloproliferative neoplasm
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Philadelphia-negative myeloproliferative neoplasms (MPNs) are a group of clonal disorders that are characterized by excessive proliferation of abnormal myeloid precursors and mature cells. Somatic driver mutations in the JAK2, CALR, and MPL genes serve as major diagnostic criteria in the classification of the MPNs, namely polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Although initially thought to be mutually exclusive, recent studies have reported the co-existence of JAK2, MPL, and CALR mutations. In this case report, we describe a case of a Philadelphia-negative myeloproliferative neoplasm harboring mutations in the CALR [NM_004343.3:c.1092_1143del52 (NP_004334.1:p.Leu367Thrfs)] and MPL [NM_005373.2:c.1543T>A (NP_005364.1:p.Try515Arg)] genes. Given the rarity of documented co-occurrence of driver mutations in these two genes and the concomitant paucity of data regarding management of patients harboring mutations in both these genes simultaneously, there are no clear guidelines for the treatment of patients with these mutation patterns and hence it is difficult to assess the true relevance of this genotype. The fact that both the MPL and CALR genes are a part of the JAK-STAT pathway could, however, assist in the clinical decision-making process.
KeywordsCALR Doubly mutated Essential thrombocythemia MPL Myeloproliferative neoplasm Next-generation sequencing
We would like to thank the team from GenePath Diagnostics: Asawari Pilankar, Ashwini Bapat, Karthik Ganesan, Kavita Khatod, Neher Parimoo, Priyanka Gangodkar, Purvi Majethia, Trupti Ragte-Wathare, and Vidula Sengaonkar.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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