Co-occurrence of CALR and MPL somatic mutations in an Indian patient with a Philadelphia-negative myeloproliferative neoplasm

AbstractPhiladelphia-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 theJAK2,CALR, andMPL 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 ofJAK2,MPL, andCALR mutations. In this case report, we describe a case of a Philadelphia-negative myeloproliferative neoplasm harboring mutations in theCALR [NM_004343.3:c.1092_1143del52 (NP_004334.1:p.Leu367Thrfs)] andMPL [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 theMPL andCALR genes are a part of the JAK-STAT pathway could, however, assist in the clinical decision-making process.

Source: Journal of Hematopathology - June 7, 2019 Category: Pathology Source Type: research