Clinical and hematological relevance of JAK2 V617F and CALR mutations in BCR-ABL-negative ET patients

ABSTRACT

Background: Classical BCR-ABL1-negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis frequently harbor JAK2, MPL, and CALR somatic mutations.

Methods: AS-PCR for JAK2 V617F, pyrosequencing for MPL W515L/K, and PCR-fragment analysis for CALR exon 9 mutations were established to analyze genomic DNA isolated from peripheral blood samples of 58 newly diagnosed ET patients in Thailand.

Results: JAK2 V617F was detected in 41 patients (71%) and CALR exon 9 mutation was positive in eight patients (14%), whereas no mutation of MPL W515L/K was observed in this study. Patients with CALR mutation were older (p = 0.023) and exhibited lower number of platelet count (p = 0.041) than patients without CALR mutation. Two previously known CALR mutation types were identified in this study (six patients with CALR-type 1 and two patients with CALR-type 2). Additionally, no co-existence of JAK2 V617F and CALR mutations was identified in this work.

Conclusion: We reported the frequency of JAK2 V617F, MPL W515L/K, and CALR mutations in Thai patients with ET. Clinical and hematological phenotypes of patients were associated with JAK2 and CALR mutation statuses. The combination of laboratory testing for the detection of JAK2, CALR, and MPL mutations is necessary to improve the diagnosis and classification of BCR-ABL1-negative MPN.

KEYWORDS:

• BCR-ABL1-negative MPN
• essential thrombocythemia
• calreticulin
• JAK2 V617F
• frameshift mutation

Acknowledgments

We thank Dr Suporn Chuncharunee and staffs at Division of Hematology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University for their valuable help especially in obtaining samples and clinical data. The authors thank Ramathibodi Cancer Center, Ramathibodi Hospital, Mahidol University for the support of reagents and chemicals.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

N. Limsuwanachot is a senior scientist in Molecular Oncology group, pursuing research in myeloproliferative neoplasm, biomarkers of leukemia, and molecular pathology.

B. Rerkamnuaychoke is a head of Human Genetic Laboratory, pursuing research in molecular oncology and forensic genetics.

S. Chuncharunee is a senior doctor, pursuing research in hematological malignancy and blood disorders.

T. Pauwilai is a senior doctor, pursuing research in hematological malignancy and myeloma.

R. Singdong is a lecturer at the Department of Medical Technology, pursuing research in myeloproliferative neoplasm.

P. Rujirachaivej is a medical technologist, pursuing research in myelodysplastic syndrome and molecular pathology.

T. Chareonsirisuthigul is a medical doctor, pursuing research in genetic diseases and molecular pathology.

T. Siriboonpiputtana is a senior lecturer and leader of Molecular Oncology group, pursuing research in biomarkers of leukemia and cancer stem cell.

Additional information

Funding

This work was supported by Ramathibodi Cancer Center, Ramathibodi Hospital, Mahidol University.