ISSN 2997-1036
International Journal of Hematology | Vol. 8, No. 8, August 2017 | pp. 57–64
DOI: 10.46882/2017/IJH/000092
Original Article
Title: Clinical profile and molecular characterization of CALR exon 9 insertion and deletion variants in essential thrombocythemia
Names of Authors: G. M. Babalola¹, I. N. Nwosu², K. S. Abubakar³
Authors’ Affiliations: ¹Department of Haematology and Blood Transfusion, Lagos University Teaching Hospital, Lagos, Nigeria; ²Department of Medicine, University of Nigeria, Nsukka, Nigeria; ³Department of Pathology, Bayero University, Kano, Nigeria
Abstract: Calreticulin (CALR) exon 9 mutations represent the second most frequent driver alteration in BCR-ABL1-negative myeloproliferative neoplasms, but the distinct hematological variations between Type 1 and Type 2 variants remain unresolved in sub-Saharan cohorts. This cross-sectional study investigated the molecular profiles of 48 adult patients presenting with JAK2-negative essential thrombocythemia. Genomic DNA was isolated from peripheral blood leucocytes, followed by polymerase chain reaction amplification and direct Sanger sequencing to determine mutation architecture. CALR mutations were detected in 37.5% (18 of 48) of the patients. Molecular characterization identified Type 1 mutations (a 52-base pair deletion) in 61.1% (11 of 18) of positive cases, while Type 2 mutations (a 5-base pair insertion) accounted for 38.9% (7 of 18). Patients harboring Type 1 deletion variants exhibited significantly higher mean baseline platelet counts (892.4 ± 114.0 × 10⁹/L versus 612.5 ± 84.0 × 10⁹/L, P < 0.05) and lower total white blood cell counts compared to Type 2 cohorts. No thromboembolic events were recorded during a 12-month follow-up window among CALR-positive individuals. Screening for specific calreticulin mutation subclasses provides valuable prognostic utility, refining risk-stratified management protocols in essential thrombocythemia.
Keywords: Essential thrombocythemia, Calreticulin mutation, deletion variants, insertion variants, molecular genetics
Manuscript Timeline: Received: May 12, 2017; Revised: June 22, 2017; Accepted: July 10, 2017; Published: August 16, 2017