Frequency and Molecular Characteristics of Calreticulin Gene <b><i>(CALR)</i></b> Mutations in Patients with <b><i>JAK2</i></b>-Negative Myeloproliferative Neoplasms

Abstract

In 2013, Nangalia et al. and Klampfl et al. found a recurrent and abundant mutation in the calreticulin gene (CALR), mutually exclusive with JAK2 and MPL alterations. At present, the data concerning the new mutation, i.e. its prevalence, allele burden and clinical significance, are scarce. We report the incidence and molecular characteristics of CALR mutations in a group of 184 Polish patients with myeloproliferative neoplasms (MPNs). Clinical data analysis revealed significant differences between JAK2 V617F-mutated and CALR-mutated groups. In essential thrombocythemia patients, hemoglobin levels and leukocyte counts were significantly higher in JAK2-positive than in CALR-positive patients (p = 0.023 and p = 0.017, respectively), but the CALR-positive patients had significantly higher platelet counts (p = 0.022). Patients harboring CALR mutations were also younger at the time of diagnosis (p = 0.039). In primary myelofibrosis patients, the degree of anemia was less severe in those who were CALR exon 9 mutation-positive than in those who were JAK2 V617F-positive (p = 0.048). © 2014 S. Karger AG, Basel

The Prevalence ofJAK2,MPL, andCALRMutations in Chinese Patients WithBCR-ABL1–Negative Myeloproliferative Neoplasms

“…3,[5][6][7]9,16,17,[24][25][26][27][28][29][30][31][32] Unlike the similar mutation frequency of JAK2 exon 12, MPL exon 10, and CALR exon 9 in different studies, the mutation rate of JAK2 V617F in PV ranged from 65% to 98%, probably due to either population differences among various ethnic backgrounds or different sensitivity of detection methods.…”

“…Wojtaszewska et al 24 1/117 (0.9) 0/14 (0) Chen et al 25 4/147 (2.7) Tefferi et al 26 8/292 (2.7) 21/267 (7.9) Wu et al 27 4/80 (5.0) 3/50 (6.0) Rumi et al 28 25/617 (4.1) Tefferi et al 29 11/402 (2.7) Pietra et al 30 Copyright of American Journal of Clinical Pathology is the property of American Society of Clinical Pathologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.…”

Mutant calreticulin‐expressing cells induce monocyte hyperreactivity through a paracrine mechanism

“…This difference remains unexplained but hints at differential mechanisms of disease pathogenesis. In addition, several groups reported that CALR mutant ET patients have higher platelet counts than JAK2‐ V617F mutant patients . One group generated a mutant‐specific CALR antibody and noted more intense mutant CALR expression in megakaryocytes compared to other cells in the bone marrow, suggesting that mutant CALR may have a more prominent, lineage‐specific effect on megakaryocytes than does JAK2‐ V617F .…”

CALR (calreticulin)

“…CALR was also identified in a subset of patients with refractory anemia with ringed sideroblasts associated with marked thrombocytosis, but not in other hematological malignancies (Klampfl, et al 2013). These finding were confirmed by several research groups (Grinsztejn, et al 2016;Haslam, et al 2016;Labastida-Mercado, et al 2015;Machado-Neto, et al 2015;Monte-Mor, et al 2016;Nunes, et al 2015;Shirane, et al 2015;Wojtaszewska, et al 2015;. Over fifty different CALR mutations in exon 9 have been described, however the most frequent mutations (approximately 80%) are classified as type-1 (L367fs*46, deletion of 52bp) and type-2 (K385fs*47, insertion of 5bp).…”