Comparative thrombotic risk associated with CALR1, CALR2, and JAK2 V617F mutations in essential thrombocythemia

Abstract

Thrombosis is a common complication of Essential Thrombocythemia (ET) and is responsible for significant morbidity and mortality in affected individuals. The JAK2 V617F mutation is a well-established risk factor for thrombosis in ET, with a reported prevalence of approximately 50% in patients with ET. However, there is increasing evidence that other mutations, including CALR mutations, also independently confer increased thrombotic risk in ET. CALR functions as a chaperone protein that screens misfolded proteins in the endoplasmic reticulum and prevents transition to the Golgi apparatus and, ultimately, to the cell surface. CALR mutations are exon 9 frameshift mutations due to 52-base pair deletion in type 1 or 5-base pair insertion in type 2.JAK2 and CALR mutations have been proposed to represent two distinct subtypes of ET due to their significant differences in thrombosis risk and disease progression. Therefore, we conducted a systematic review and meta-analysis comparing the cumulative thrombotic risk between different CALR mutation types (type 1 and type 2), and JAK2 V617F mutation in ET.We searched PubMed, Google Scholar, MEDLINE OVID, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases to identify relevant peer-reviewed studies published from database inception to January 2023 without any language restrictions. The overall odds ratio (OR) was computed