Abstract
Mutations of the multifunctional protein calreticulin (CALR) are recognised as one of the main driver alterations involved in the pathogenesis of Philadelphia negative myeloproliferative neoplasms (Ph– MPN) and also represent a major diagnostic criterion in the most recent World Health Organization classification of myeloid neoplasms. Nowadays, quantitative assessment of the driver mutations is gaining importance, as recent studies demonstrated the clinical relevance of the mutation load reflecting the size of the mutant clone. Here, we performed for the first time a manual and automated quantitative assessment of the CALR mutation load at protein level using CAL2, a recently developed CALR mutation specific monoclonal antibody, on a cohort of 117 patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) and compared the CALR protein mutation loads with the CALR mutation load values established by a molecular assay. Eighteen different CALR mutations were detected in the cohort of the 91 CALR mutant cases. Mutation loads of the CALR mutations were between 13% and 94% with mean value in PMF cases significantly higher than ET cases (49.94 vs 41.09; t-test, p=0.004). Cases without CALR mutation (n=26) showed no or only minimal labelling with the CAL2 antibody, while all 18 different types of CALR mutations were associated with CAL2 labelling. The CALR mutation load showed a significant correlation (p=0.03) with the occurrence of major thrombotic events, with higher mutation load in patients presenting with these complications. We report a 100% concordance between the mutation status determined by immunohistochemistry and the CALR molecular assay, and we extend the applicability of this approach to 16 rare CALR mutations previously not analysed at protein level.
| Language | English |
|---|---|
| Journal | Pathology |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2019 |
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Keywords
- CAL2 immunohistochemistry
- calreticulin mutation
- mutation load
- Myeloproliferative neoplasms
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Calreticulin mutation specific CAL2 immunohistochemistry accurately identifies rare calreticulin mutations in myeloproliferative neoplasms. / Mózes, Réka; Gángó, Ambrus; Sulák, Adrienn; Vida, Livia; Reiniger, Lilla; Timár, Botond; Krenács, T.; Alizadeh, Hussain; Masszi, T.; Gaál-Weisinger, Júlia; Demeter, J.; Csomor, Judit; Matolcsy, A.; Kajtár, Béla; Bödör, Csaba.
In: Pathology, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Calreticulin mutation specific CAL2 immunohistochemistry accurately identifies rare calreticulin mutations in myeloproliferative neoplasms
AU - Mózes, Réka
AU - Gángó, Ambrus
AU - Sulák, Adrienn
AU - Vida, Livia
AU - Reiniger, Lilla
AU - Timár, Botond
AU - Krenács, T.
AU - Alizadeh, Hussain
AU - Masszi, T.
AU - Gaál-Weisinger, Júlia
AU - Demeter, J.
AU - Csomor, Judit
AU - Matolcsy, A.
AU - Kajtár, Béla
AU - Bödör, Csaba
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Mutations of the multifunctional protein calreticulin (CALR) are recognised as one of the main driver alterations involved in the pathogenesis of Philadelphia negative myeloproliferative neoplasms (Ph– MPN) and also represent a major diagnostic criterion in the most recent World Health Organization classification of myeloid neoplasms. Nowadays, quantitative assessment of the driver mutations is gaining importance, as recent studies demonstrated the clinical relevance of the mutation load reflecting the size of the mutant clone. Here, we performed for the first time a manual and automated quantitative assessment of the CALR mutation load at protein level using CAL2, a recently developed CALR mutation specific monoclonal antibody, on a cohort of 117 patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) and compared the CALR protein mutation loads with the CALR mutation load values established by a molecular assay. Eighteen different CALR mutations were detected in the cohort of the 91 CALR mutant cases. Mutation loads of the CALR mutations were between 13% and 94% with mean value in PMF cases significantly higher than ET cases (49.94 vs 41.09; t-test, p=0.004). Cases without CALR mutation (n=26) showed no or only minimal labelling with the CAL2 antibody, while all 18 different types of CALR mutations were associated with CAL2 labelling. The CALR mutation load showed a significant correlation (p=0.03) with the occurrence of major thrombotic events, with higher mutation load in patients presenting with these complications. We report a 100% concordance between the mutation status determined by immunohistochemistry and the CALR molecular assay, and we extend the applicability of this approach to 16 rare CALR mutations previously not analysed at protein level.
AB - Mutations of the multifunctional protein calreticulin (CALR) are recognised as one of the main driver alterations involved in the pathogenesis of Philadelphia negative myeloproliferative neoplasms (Ph– MPN) and also represent a major diagnostic criterion in the most recent World Health Organization classification of myeloid neoplasms. Nowadays, quantitative assessment of the driver mutations is gaining importance, as recent studies demonstrated the clinical relevance of the mutation load reflecting the size of the mutant clone. Here, we performed for the first time a manual and automated quantitative assessment of the CALR mutation load at protein level using CAL2, a recently developed CALR mutation specific monoclonal antibody, on a cohort of 117 patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) and compared the CALR protein mutation loads with the CALR mutation load values established by a molecular assay. Eighteen different CALR mutations were detected in the cohort of the 91 CALR mutant cases. Mutation loads of the CALR mutations were between 13% and 94% with mean value in PMF cases significantly higher than ET cases (49.94 vs 41.09; t-test, p=0.004). Cases without CALR mutation (n=26) showed no or only minimal labelling with the CAL2 antibody, while all 18 different types of CALR mutations were associated with CAL2 labelling. The CALR mutation load showed a significant correlation (p=0.03) with the occurrence of major thrombotic events, with higher mutation load in patients presenting with these complications. We report a 100% concordance between the mutation status determined by immunohistochemistry and the CALR molecular assay, and we extend the applicability of this approach to 16 rare CALR mutations previously not analysed at protein level.
KW - CAL2 immunohistochemistry
KW - calreticulin mutation
KW - mutation load
KW - Myeloproliferative neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85059235901&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059235901&partnerID=8YFLogxK
U2 - 10.1016/j.pathol.2018.11.007
DO - 10.1016/j.pathol.2018.11.007
M3 - Article
JO - Pathology
T2 - Pathology
JF - Pathology
SN - 0031-3025
ER -