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CALR mutation burden in essential thrombocythemia and disease outcome
Paola Guglielmelli1, Natasha Szuber2,3,4, Naseema Gangat5
1Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Division of Hematology, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.
Blood
|January 22, 2024
Summary
High variant allele frequency (≥60%) in calreticulin (CALR) mutations is linked to shorter survival without myelofibrosis in essential thrombocythemia patients. This association is particularly noted for CALR type-1 and indeterminate mutations.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Essential thrombocythemia is a myeloproliferative neoplasm.
- Calreticulin (CALR) mutations are common drivers in essential thrombocythemia.
- Myelofibrosis is a potential complication of essential thrombocythemia.
Purpose of the Study:
- To investigate the prognostic significance of variant allele frequency (VAF) in CALR-mutated essential thrombocythemia.
- To determine if VAF impacts the risk of developing myelofibrosis.
Main Methods:
- Retrospective analysis of 281 patients with essential thrombocythemia and CALR mutations.
- Assessment of variant allele frequency (VAF) for CALR mutations.
- Survival analysis for myelofibrosis-free survival.
Main Results:
- A variant allele frequency (VAF) of ≥60% in CALR mutations was associated with significantly shortened myelofibrosis-free survival.
- This association was most pronounced in patients with CALR type-1 and CALR type-indeterminate mutations.
- No significant association was observed for other CALR mutation types.
Conclusions:
- High VAF (≥60%) of CALR mutations is a potential adverse prognostic marker in essential thrombocythemia.
- Monitoring VAF may aid in risk stratification for myelofibrosis development.
- Further research is warranted to explore the underlying mechanisms linking high VAF to disease progression.
