Laboratory Assessment of Patients with Chronic Myeloproliferative Diseases

慢性骨髓增生性疾病患者的实验室评估

• 批准号: 7593142
• 负责人: Irina Maric
• 金额: $ 1.1万
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7593142
• 关键词: Biological Assay; Biological Markers; Blood Platelets; Cells; Chronic; Chronic Myeloproliferative Disorder; Collaborations; Condition; Detection; Diagnosis; Diagnostic; Disease; Erythrocytes; Evaluation; Exclusion; Flow Cytometry; Genes; Goals; Hematologic Neoplasms; Hematopoietic; Hemorrhagic Thrombocythemia; Indium; Janus kinase 2; Laboratories; Leukocytes; Membrane Proteins; Molecular; Mutation; Myelogenous; Myeloid Cells; Myeloproliferative disease; Natural History; Pathologic; Patients; Phenylalanine; Phosphorylation; Play; Point Mutation; Polycythemia Vera; Positioning Attribute; Primary Myelofibrosis; Proteins; Reporting; Role; Staging; Stem cells; Subcategory; Testing; Today; Valine; neutrophil; novel; prospective

The three main classic chronic myeloproliferative disorders recognized today are polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis. A lack of reliable and readily available biomarkers for the chronic myeloproliferative disorders has led to diagnostic difficulties in the past. The diagnosis of both PV and ET has largely been by exclusion. However, recent reports described that 76% to 97% of patients with PV, 29% to 57% of patients with ET and 50% of patients with IMF have a somatic point mutation in JAK2. The mutation, JAK V617F, is not found in healthy subjects and is associated with constitutive phosphorylation of JAK2 and its downstream effectors. Laboratory evaluation of patients with suspected chronic myeloproliferative disorders includes molecular testing for the presence of the JAK2 mutation and immunophenotypic analysis of hematopoietic cells by flow cytometry. Morphologic review will be performed if material is available. We have developed in the past year novel RT-PCR/RFLP assay for detection of the JAK V617F mutation. We have also developed a flow cytometric panel for chronic myeloid disorders, which includes evaluation of CD177 expression on myeloid elements in patients with and without JAK2 V617F mutation. One of our goals is to investigate the possible role of neutrophil expression of CD177 gp as a biomarker of chronic myeloproliferative disorders. Changes in neutrophil expression of CD177 gp alone or in combination with other neutrophil membrane proteins might be useful biomarkers for the diagnosis or staging of ET or PV.

目前公认的三种主要的经典慢性骨髓增生性疾病是真性红细胞增多症、原发性血小板增多症和特发性骨髓纤维化。缺乏可靠的和容易获得的生物标志物的慢性骨髓增生性疾病导致诊断困难，在过去。PV和ET的诊断在很大程度上是通过排除法进行的。然而，最近的报道描述了76%至97%的PV患者、29%至57%的ET患者和50%的IMF患者在JAK 2中具有体细胞点突变。 JAK V617 F突变在健康受试者中未发现，并且与JAK 2及其下游效应物的组成性磷酸化相关。疑似慢性骨髓增生性疾病患者的实验室评估包括JAK 2突变存在的分子检测和通过流式细胞术进行的造血细胞免疫表型分析。如果材料可用，将进行形态学审查。在过去的一年中，我们开发了新的RT-PCR/RFLP检测JAK V617 F突变。 我们还开发了一种用于慢性髓系疾病的流式细胞仪，其中包括评估有和没有JAK 2 V617 F突变的患者骨髓成分上的CD 177表达。我们的目标之一是研究中性粒细胞表达CD 177 gp作为慢性骨髓增生性疾病的生物标志物的可能作用。 中性粒细胞CD 177 gp表达的变化单独或与其他中性粒细胞膜蛋白的组合可能是有用的生物标志物的诊断或分期的ET或PV。