골수증식종양 환자에서 MPL W515 돌연변이 빈도와 임상혈액학적 특징
Frequency and Clinicohematologic Characteristics of MPL W515 Mutations in Patients with Myeloproliferative Neoplasms
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배경: 최근 myeloproliferative leukemia (MPL) W515 돌연변이가 골수증식종양(MPN)에서 발견되었고, 새로운 분자유전학적 표지자로제시되었다. 본 연구에서는 MPL W515 돌연변이 빈도 및 임상혈액학적 지표들과의 상관성을 알아보고자 하였다. 방법: 진성적혈구증가증(PV) 31명, 일차골수섬유증(PMF) 17명, 진성고혈소판증(ET) 106명을 포함한 총 154명의 MPN 환자를 대상으로 MPL W515 돌연변이를 실시간중합효소연쇄반응으로 검출하였고, 직접염기서열분석을 통해 재확인하였다. 결과: 전체 154명의 환자 중 5명(3.2%)의 환자에서 MPL W515 돌연변이가 확인되었다. 이들은 모두 ET환자였고, JAK2 V617F 음성으로, JAK2 V617F 음성 ET환자의 12.5%를 차지하였다. MPL W515 돌연변이 양성 ET 환자들은 MPL W515 음성이나 JAK2 V617F 양성 ET 환자에 비해 총백혈구수와 혈색소가 유의하게 낮았다. 결론: MPL W515 돌연변이는 JAK2 V617F 음성 MPN 환자의 진단에 중요한 표지자로 이용할 수 있으며, 심한 빈혈 양상이나 낮은 백혈구수 등 특징적인 임상혈액학적 소견을 가져 JAK2 V617F 음성 ET 및 다른 MPN 병태생리의 이해에 도움이 될 것이다.
Abstract
Background: Recently, myeloproliferative leukemia (MPL) W515 mutations have been reported to be molecular markers for myeloproliferative neoplasms (MPNs). We studied the association between MPL W515 mutations and the clinico-hematological features of patients with MPNs. Methods: Our study included 154 consecutive patients diagnosed with MPNs (31 had polycythemia vera [PV]; 106, essential thrombocythemia [ET]; and 17, primary myelofibrosis [PMF]). MPL W515 mutations were detected by real-time PCR and direct sequencing methods. Results: The MPL W515L mutation was found in 4 patients and the MPL W515A mutation was detected in 1 patient. These 5 patients were diagnosed with JAK2 V617F-negative ET, and they accounted for 12.5% of patients with JAK2 V617F-negative ET. The patients with MPL W515-positive ET showed significantly lower hemoglobin levels and WBC counts than did patients with MPL W515-negative ET or JAK2 V617F-positive ET. Conclusions: MPL W515 mutation is a useful diagnostic marker for JAK2 V617F-negative MPNs and it is associated with specific hematologic characteristics such as lower hemoglobin levels and WBC counts.
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