Clinicopathologic characterization of malignant progression of myelodysplastic syndrome

骨髓增生异常综合征恶性进展的临床病理特征

• 批准号: 14570138
• 负责人: ITO Masafumi
• 金额: $ 2.24万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570138/
• 关键词: myelodysplastic syndrome (MDS); fetal type hemoglobin (HbF); bone marrow pathology; hypoplastic MDS; aplastic anemia; stress erythropoiesis; leukemic transformation; 骨髄異形成症候群; 髄外造血; アポトーシス; 免疫組織化学; p53

On this project, we have set up the aim to examine the pathological mechanism of malignant progression of myelodysplastic syndrome (MDS). We have newly obtained the results as follows;1.We have developed originally the new polyclonal antibody specific to fetal type hemoglobin (HbF) by immunizing synthetic peptides of human HbF (Int J Hematol 74:277-280,2001). This antibody has beneficial utility for pathologic examination of bone marrow pathology.2.Differential diagnosis between aplastic anemia and hypoplastic MDS is quite difficult. We could demonstrate the difference of HbF synthetic erythroblasts and p53 expression within these diseases. We have presented the possibility of the differential diagnosis between them (Int J Hematol 75:257-260,2002).3.HbF synthetic erythroblasts in extramedullary hematopoiesis are the landmark of its pathologic diagnosis. This phenomena is enhanced by stress erythropoiesis in bone marrow and extramedullary sites (Haematologica 87:323-325,2002).4.In MDS, F blasts and p53 positive cells are increased significantly than normal control and stress erythropoiesis (Leukemia 16:1478-1483,2002).5.Ineffective erythropoiesis in MDS is caused by apoptotic event of F-blasts to F-cells (Leukemia 16:1478-1483,2002).6.F blast production in MDS is correlated strongly with up-regulation of inducible nitric oxide syntheses (Ann Hematol 81:548-550,2002). This meaning is the basic hypothesis of HbF synthesis in MDS.By retrospective clinicopathologic study of MDS cases, the cases with chromosome 7 abnormality show the characteristic pathological changes. These cases had high risk of malignant progression and resistance to chemotherapy. Early diagnosis of this type could improve the prognosis.

在这个项目中，我们建立了研究骨髓增生异常综合征(MDS)恶性进展的病理机制的目标。主要研究结果如下：1.首次将合成人HBF多肽免疫人HBF(Int J hematol 74：277-280,2001)，研制出针对HBF的新型多克隆抗体。该抗体对骨髓病理检查具有一定的实用价值。2.再生障碍性贫血与增生性MDS的鉴别诊断相当困难。我们可以证明HBF合成红细胞和P53的表达在这些疾病中的差异。我们提出了两者鉴别诊断的可能性(Int J hematol 75：257-260,2002)。3.髓外造血中的HbF合成红细胞是其病理诊断的标志。在MDS中，F母细胞和P53阳性细胞显著高于正常对照组和应激性红细胞生成(白血病16：1478-1483,2002)。5.MDS中无效的红细胞生成是由F-母细胞对F-细胞的凋亡事件引起的(白血病16：1478-1483,2002)。6.MDS中F母细胞的产生与诱导性一氧化氮合成的上调密切相关(Ann hematol 81：548-550,2002)。这一意义是MDS患者HBF合成的基本假设。通过对MDS病例的回顾性临床病理研究，发现7号染色体异常的病例表现出特征性的病理改变。这些病例恶性进展的风险很高，对化疗耐药。该类型的早期诊断可改善预后。

项目成果

Atsuko Nakagawa: "Fetal cytotoxic T-cell proliferation in chronic active Epstein-Barr virus infection in childhood"Am J Cli Pathol. 117. 283-290 (2002)

Atsuko Nakakawa：“儿童期慢性活动性 Epstein-Barr 病毒感染中胎儿细胞毒性 T 细胞增殖”Am J Cli Pathol。

Yuka Hirose: "Successful treatment with Imatinib mesylate of a CML patient in me gakaryoblastic crisis with severe fibrosis"Int J Hematol. 76. 349-353 (2002)

Yuka Hirose：“甲磺酸伊马替尼成功治疗患有严重纤维化的 CML 患者”Int J Hematol。

Masafumi Ito: "Prevalence of Intravascular Large B-cell Lymphoma with Bone Marrow Involvement at Initial Presentation"Int J Hematol. 77. 159-163 (2003)

Masafumi Ito：“血管内大 B 细胞淋巴瘤初次出现时累及骨髓的患病率”Int J Hematol。

伊藤雅文: "臓器移植病理の新展開:骨髄移植"移植. 38. 59-64 (2003)

伊藤雅文：“器官移植病理学的新进展：骨髓移植” 移植 38. 59-64 (2003)。

Jw Choi, Y Kim, M Fujino, M Ito: "Significance of fetal hemoglobin-containing erythroblasts (F blasts) and the F blast/F cell ratio in myelodysplastic syndromes"Leukemia. 16. 1478-1483 (2002)

Jw Choi、Y Kim、M Fujino、M Ito：“含胎儿血红蛋白的成红细胞（F 母细胞）和 F 母细胞/F 细胞比率在骨髓增生异常综合征中的意义”白血病。