JAK2 , CALR , MPL , and ASXL1 Mutations in 136 Thai Patients with Philadelphia-Negative Myeloproliferative Neoplasms and Their Correlations with Clinical Outcomes
Dollapak Apipongrat MMT¹, Tontanai Numbenjapon MD¹, Thirayost Nimmanon MD, PhD², Pasra Arnutti PhD²
Affiliation : ¹ Division of Hematology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand ² Department of Pathology, Phramongkutklao College of Medicine, Bangkok, Thailand
Background : Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPN) are a group of hematological malignancies, including
polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). Mutations of JAK2 , CALR , MPL , and ASXL1 are associated
with carcinogenesis and clinical characteristics of Ph-negative MPN. However, the availability of the data regarding these mutations is relatively
limited in Thai population.
Objective : To investigate these mutations in Thai Ph-negative MPN patients. Materials and Methods : One hundred thirty-six MPN (48 PV, 72 ET, and 16 PMF) cases were enrolled. Mutations of JAK2 V617F and MPL W515L/K mutations were investigated using allele-specific PCR (AS-PCR) and confirmed by sequencing. CALR and ASXL1 mutations were investigated using Sanger sequencing.
Results : The JAK2 V617F mutation was detected in 83.3% of PV, 66.6% of ET, and 50.0% of PMF, and correlated with higher RBC, WBC, and PLT counts in PV. CALR mutations were detected in 16.7% of ET and 12.5% of PMF and associated with a higher PLT count in ET. The MPL W515L mutation was detected in one PMF patient. ASXL1 mutations were detected in 6.3% of PV, 8.3% of ET, and 12.4% of PMF, with c.1954G>A being the preponderant mutational form. ASXL1 mutations increased the risk (RR 27.6) and accelerated the onset of AML transformation.
Conclusion : The present study provided the prevalence and clinical correlation of JAK2 , CALR , MPL , and ASXL1 mutations among Thai Ph-negative MPN patients. The association of ASXL1 mutations with adverse clinical outcomes suggested the potential usefulness of these mutations as a prognostic marker for Ph-negative MPN patients.
Received 22 December 2020 | Revised 11 March 2021 | Accepted 12 March 2021
doi.org/10.35755/jmedassocthai.2021.05.12344
Keywords : JAK2 , MPL , CALR , ASXL1 , Thai, Philadelphia-negative myeloproliferative neoplasm (MPN)
