MPL S505N 돌연변이 양성인 일차골수섬유증 1예
Primary Myelofibrosis with MPL S505N Mutation: The First Case Reported in Korea
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MPL 돌연변이는 만성골수증식종양(chronic myeloproliferative neoplasm, MPN)의 중요한 분자 표지자이다. MPL W515 돌연변이가 MPN에서 과오돌연변이로 인한 hot spot이지만, MPL S505 돌연변이가 가족성, 비가족성 MPN에서 드물게 보고되었다. 72세의 남성이 어지러움과 코피를 주소로 내원하였다. 전체혈구계산에서 백혈구증가증, 빈혈, 혈소판감소증이 관찰되었고 말초혈액도말에서 눈물방울세포, 유핵적혈구와 골수모세포가 관찰되었다. 골수흡인은 실패했고 말초혈액에 희석되었다. 골수생검에서 높은 세포충실도, 비정상 거대핵세포의 증식, 그리고 3단계의 reticulin 섬유화가 관찰되었다. 세포유전검사에서는 46,XY,del(13)(q12q22)[19]/46,XY[1]이 관찰되었다. 분자검사에서 JAK2 V617F, BCR/ABL 전위, JAK2 엑손 12 그리고 CALR 엑손 9 돌연변이는 관찰되지 않았다. MPL S505N 돌연변이는 유전자 클로닝 후 실시된 colony PCR-Sanger sequencing기법으로 양성임이 확인되었다. 이들 소견을 종합하여 명백한 일차골수섬유증(overt PMF)으로 진단하였다. 하지만 구강세포와 T림프구 그리고 가족에서 본 돌연변이 검사를 시행하지 않아 이 돌연변이가 가족성인지 비가족성인지 판단할 수 없었다. 환자는 첫 내원 후 6개월 후 폐렴과 패혈증으로 사망했다. PMF로 진단 후 생존기간 동안 혈전증에 의한 증상과 주요출혈사건은 없었다. 이에 MPL S505N 돌연변이가 동반된 PMF의 국내 첫 증례로 문헌고찰과 함께 보고하는 바이다.
Abstract
MPL mutation is an important molecular marker in myeloproliferative neoplasms (MPN). Although MPL W515 is a hot spot for missense mutations in MPN, MPL S505 mutations have been reported in both familial and non-familial MPN. A 72-year-old male visited the hospital, complaining mainly of dizziness and epistaxis. Leukocytosis, anemia, thrombocytopenia, tear drop cells, nucleated RBCs, and myeloblasts were observed in both complete blood cell counts and peripheral blood smears. Bone marrow aspiration failed due to dilution with peripheral blood. BM biopsy indicated hypercellular marrow, megakaryocytic proliferation with atypia, and grade 3 reticulin fibrosis. Conventional cytogenetics results were as follows: 46,XY,del(13)(q12q22)[19]/46,XY[1]. Molecular studies did not detect JAK2 V617F, BCR/ABL translocation, JAK2 exon 12, and CALR exon 9 mutations. The MPL S505N mutation was verified by colony PCR and Sanger sequencing following gene cloning. Based on the above findings, a diagnosis of overt primary myelofibrosis (PMF) was indicated. Mutation studies of buccal and T cells were not conducted. Further, family members were not subjected to mutation studies. Therefore, we were unable to determine whether this mutation was familial or non-familial. Six months after the first visit to the hospital, the patient died due to pneumonia and sepsis. Thrombotic symptoms or major bleeding events did not develop during the survival period following diagnosis of PMF. To the best of our knowledge, this may be the first reported case of PMF with the MPL S505N mutation in Korea.
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