다발성골수종 환자에서 질병 진행 예측인자로서 혈청 Thrombopoietin과 임상지표 분석
The Analysis of Thrombopoietin and Clinical Parameters as a Marker for Disease Progression in Patients with Multiple Myeloma
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배경 : 다발성골수종은 골수 내 악성 세포의 증식으로 인해 조 혈 기능의 저하를 초래하는 질환이다. 최근 혈소판이 정상이지만 thrombopoietin (TPO)의 증가는 부적절한 조혈작용의 지표이 며 조혈작용을 유지하려는 보상기전이라는 연구결과가 있었다. 저자들은 다발성 골수종 환자에서 TPO와 임상지표와의 분석을 통해 질병진행인자로 고려할 수 있는지를 알아보고자 하였다. 방법 : 27명의 환자로부터 채취한 70개의 혈액을 통해 혈청 TPO를 측정하였다. 13명은 새롭게 다발성골수종으로 진단받은 환자였으며, 14명은 이전에 진단받고 추적관찰 중인 환자였다. 혈청 TPO 및 혈소판 수에 따른 백혈구, 혈색소치, 크레아티닌, 칼슘, M-단백, 단백질, 알부민 그리고 β2-micoglobulin 등의 임상 지표에 대해 비교 분석하였다. 정상 대조군 20명의 혈청 TPO 농도범위는 6-69 pg/mL이었다. 결과 : 혈청 TPO 농도는 정상 대조군 및 정상 혈소판 수를 보 이는 다발성골수종 환자와 비교해 혈소판 수 저하를 보이는 다발 성골수종 환자에서 통계적으로 의미 있게 높았다(median TPO: 293.0 pg/mL vs 59.6 pg/mL and 35.6 pg/mL, P<0.0001). 혈청 TPO가 높을수록 백혈구(r=-0.293), 혈색소치(r=-0.378) 및 혈소판 수(r=-0.508)는 저하되는 음의 상관관계를 보였다 (P<0.05). TPO 증가는 정상 혈소판을 보이는 검체에서도 관찰 되었다(N=20). 혈소판 수가 정상이면서 혈청 TPO가 증가되어 있는 군은 혈청 TPO가 정상인 군에 비해 질병이환기간이 1년 이상인 환자가 많았으며, 이러한 군은 혈색소치(10.3 vs 12.9 g/ dL, P=0.025) 및 알부민(3.3 vs 4.0 g/dL, P=0.085)이 낮았 으며, M-단백 및 단백질의 수치가 높은 경향을 보였다. 결론 : 다발성골수종에서 혈청 TPO 농도는 혈소판 저하 시 증 가되어 있었으며, 부적절한 조혈작용과 관련성을 보였다. 혈소 판 저하 없이 TPO가 증가되어 있는 경우, 부적절한 조혈기능이 진행되고 있음을 예측할 수 있으며 질병 예측 인자로 고려해 볼 수 있겠다.
Abstract
Background : Multiple myeloma (MM) causes the suppression of hematopoiesis because of malignant cells in the bone marrow. Thrombopoietin (TPO) is regulated by a feedback mechanism with platelets. Recently, it was suggested that an elevated TPO without thrombocytopenia was associated with impaired hematopoiesis. We evaluated whether TPO levels could be a marker for disease progression in MM. Methods : The TPO levels were measured in 70 blood samples from 27 patients (newly/previously- diagnosed patients=13/14). We analyzed the TPO and clinical parameters, WBC, hemoglobin, creatinine, calcium, M-protein, protein, albumin, and β2-microglobulin. The TPO in 20 healthy controls ranged from 6 to 69 pg/mL. Results : The TPO levels were significantly higher in MM patients with thrombocytopenia than in patients without thrombocytopenia and the healthy controls (median TPO: 293.0 pg/mL vs 59.6 pg/mL and 35.6 pg/mL, P<0.0001). There was a negative correlation between the TPO levels and the blood cells, i.e., leukocytes (r=-0.293), hemoglobin (r=-0.378) and platelets (r=-0.508) (P<0.05). Elevated TPO were found in association with normal platelet counts (N=20). Among the samples without thrombocytopenia, especially one year after the diagnosis, the hemoglobin (10.3 vs 12.9 g/dL, P=0.025) and albumin (3.3 vs 4.0 g/dL, P=0.085) were lower and the M-protein and protein tended to be higher in patients with elevated TPO compared to those with normal TPO. Conclusions : Serum TPO was elevated with thrombocytopenia and related to impaired hematopoiesis. The elevated TPO without thrombocytopenia might be considered as impaired hematopoiesis and a marker for disease progression in patients with MM.
참고문헌 (22)
- de Sauvage FJ, "Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand", Nature, 369, pp.533~538 (1994)
- Lok S, "Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo", Nature, 369, pp.565~568 (1994)
- Bartley TD, "Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl", Cell, 77, pp.1117~1124 (1994)
- Debili N, "The Mpl receptor is expressed in the megakaryocytic lineage from late progenitors to platelets", Blood, 85, pp.391~401 (1995)
- Fielder PJ, "Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets", Blood, 87, pp.2154~2161 (1996)
- Li J, "Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics", Br J Haematol, 106, pp.345~356 (1999)
- Kuter DJ, "The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit", Blood, 85, pp.2720~2730 (1995)
- Moller P, "Plasma thrombopoietin concentrations in response to platelet transfusion therapy", Acta Haematol, 102, pp.131~134 (2000)
- Folman CC, "Analysis of the kinetics of Tpo uptake during platelet transfusion", Transfusion, 41, pp.517~521 (2001)
- Folman CC, "In multiple myeloma increased thrombopoietin (Tpo) production may be involved in the maintenance of platelet production", Eur J Haematol, 66, pp.337~341 (2001)
- Kunishima S, "Serum thrombopoietin and plasma glycocalicin concentrations as useful diagnostic markers in thrombocytopenic disorders", Eur J Haematol, 57, pp.68~71 (1996)
- Kojima S, "Measurement of endogenous plasma thrombopoietin in patients with acquired aplastic anaemia by a sensitive enzyme-linked immunosorbent assay", Br J Haematol, 97, pp.538~543 (1997)
- Schrezenmeier H, "Thrombopoietin serum levels in patients with aplastic anaemia: correlation with platelet count and persistent elevation in remission", Br J Haematol, 100, pp.571~576 (1998)
- Emmons RV, "Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction", Blood, 87, pp.4068~4071 (1996)
- Chang M, "Differential mechanisms in the regulation of endogenous levels of thrombopoietin and interleukin-11 during thrombocytopenia: insight into the regulation of platelet production", Blood, 88, pp.3354~3362 (1996)
- Meng YG, "Circulating thrombopoietin concentrations in thrombocytopenic patients, including cancer patients following chemotherapy, with or without peripheral blood progenitor cell transplantation", Br J Haematol, 95, pp.535~541 (1996)
- Kosugi S, "Circulating thrombopoietin level in chronic immune thrombocytopenic purpura", Br J Haematol, 93, pp.704~706 (1996)
- Martin TG 3rd, "Thrombopoietin levels in patients with cirrhosis before and after orthotopic liver transplantation", Ann Intern Med, 127, pp.285~288 (1997)
- Shimazaki C, "Serum thrombopoietin levels in patients undergoing autologous peripheral blood stem cell transplantation", Bone Marrow Transplant, 19, pp.771~775 (1997)
- Usuki K, "Serum thrombopoietin level in various hematological diseases", Stem Cells, 14, pp.558~565 (1996)
- Durie BG, "A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival", Cancer, 36, pp.842~854 (1975)
- Zwierzina H, "Endogenous serum thrombopoietin concentrations in patients with myelodysplastic syndromes", Leukemia, 12, pp.59~64 (1998)