Calreticulin Mutations in Bulgarian MPN Patients

Area of Science:

• Hematology
• Molecular Genetics
• Oncology

Background:

• Somatic mutations in JAK2, MPL, and CALR are key drivers in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs).
• CALR mutations, specifically in exon 9, are frequently observed in MPNs.

Purpose of the Study:

• To investigate the frequency and patterns of CALR exon 9 mutations in South-eastern patients with myeloid malignancies.
• To compare the diagnostic utility of four molecular genetic methods for CALR mutation detection.
• To assess the mutual exclusivity and clinical correlation of CALR mutations with JAK2 and MPL mutations.

Main Methods:

• Employed high-resolution melt (HRM) analysis, Sanger sequencing, semiconductor target gene sequencing, and whole exome sequencing.
• Analyzed 78 patients diagnosed with myeloid malignancies.
• Identified and characterized CALR exon 9 mutations, including types 1 and 2.

Main Results:

• Identified 14 cases (18%) with CALR exon 9 mutations among 78 patients; all diagnosed with MPN (7 primary myelofibrosis, 7 essential thrombocythemia).
• Observed mutual exclusivity between CALR exon 9, MPL exon 10, and JAK2 p.V617F mutations.
• Demonstrated full concordance among the four molecular methods for CALR mutation detection.
• Found no significant differences in hematological parameters between patients with CALR, JAK2, or MPL mutations.
• Reported CALR mutation frequency and patterns consistent with Western populations.

Conclusions:

• CALR exon 9 mutations are a significant finding in MPNs across diverse populations, including South-eastern regions.
• The evaluated molecular methods are reliable and concordant for CALR mutation detection.
• CALR mutations, along with JAK2 and MPL, are mutually exclusive drivers in MPNs without significant impact on basic hematological parameters.