骨髓增殖性疾病四例并文献复习

 目的　总结分析4例典型骨髓增殖性疾病（MPD）患者的诊治经过,并进行相关文献复习。方法　介绍1例真性红细胞增多症、2例原发性血小板增多症和1例原发性骨髓纤维化患者的诊治经过。结果　4例患者分别采用干扰素、干扰素联合羟基脲、同胞HLA相合异基因造血干细胞移植治疗,均获得满意疗效。结论　JAK2 V617F基因突变的检测使MPD的临床诊断变得更容易;真性红细胞增多症和原发性血小板增多症患者的治疗重点为预防并发症,而对于部分高危原发性骨髓纤维化患者应考虑异基因造血干细胞移植。     

谨慎选择异基因造血干细胞移植治疗骨髓增殖性疾病:适应证探讨及疗效回顾

简要回顾了真性红细胞增多症、原发性血小板增多症和原发性骨髓纤维化等骨髓增殖性疾病的临床特点,并建议以此作为其接受异基因造血干细胞移植的适应证及选择治疗方式的依据;介绍了迄今国内外骨髓增殖性疾病的移植治疗现状以及用JAK2突变,尤其是V617F检测移植后微小残留病变的意义.     

谨慎选择异基因造血干细胞移植治疗骨髓增殖性疾病：适应证探讨及疗效回顾

 简要回顾了真性红细胞增多症、原发性血小板增多症和原发性骨髓纤维化等骨髓增殖性疾病的临床特点，并建议以此作为其接受异基因造血干细胞移植的适应证及选择治疗方式的依据；介绍了迄今国内外骨髓增殖性疾病的移植治疗现状以及用JAK2突变，尤其是V617F检测移植后微小残留病变的意义。     

胃癌合并原发性血小板增多症1例

原发性血小板增多症(essential thrombocythemia,ET)是一种造血干细胞克隆性疾病,引起外周血血小板计数(PLT)明显升高,骨髓中巨核细胞增殖旺盛,约50%~70%的患者有JAK2/V617F基因突变[1],另有一部分患者有MPL及CALR等基因突变。2008年世界卫生组织(WHO)把ET和真性红细胞增多症(PV)、原发性骨髓纤维化(PMF)同时划为BCR-ABL融合基因阴性的骨髓增殖性肿瘤(MPN)。     

骨髓增殖性肿瘤分子发病机制及治疗研究进展

介绍了第56届美国血液学会(ASH)年会前后报道的一些骨髓增殖性肿瘤(MPN)相关新基因及目前国内外治疗MPN的现状.强调MPN治疗前需要进行风险评分,原发性血小板增多症(ET)的风险评分可采用ET国际预后积分(IPSET)算法,真性红细胞增多症(PV)的风险评分可采用Tefferi算法,原发性骨髓纤维化(PMF)的风险评分可采用动态国际预后评分系统加强版(DIPSS-plus)算法.总结了异基因造血干细胞移植、静脉放血治疗、血细胞去除治疗及药物治疗的进展,尤其关注抗凝药物阿司匹林、阿那格雷、针对JAK2基因的靶向药物芦可替尼以及国内治疗PMF的主要药物沙利度胺.     

骨髓增殖性肿瘤治疗与发病机制的研究进展

bcr-abl阴性的慢性骨髓增殖性肿瘤(MPN)是起源于造血干细胞的克隆性疾病,包括真性红细胞增多症(PV)、原发性血小板增多症(ET)和原发性骨髓纤维化(PMF).随着JAK2基因突变的发现,研究者又陆续发现了许多新基因突变,使得对MPN发病机制的认识逐步深入,针对这些发病机制的新型药物也不断出现.     

原发性骨髓纤维化发病机制研究进展

 近年来通过对原发性骨髓纤维化（PMF）患者造血细胞基因突变、基因转录后修饰、细胞集落形成以及细胞周期特点等方面的研究,认为PMF是造血干祖细胞恶性克隆性增生性疾病,并将PMF与真性红细胞增多症（PV）、原发性血小板增多症（ET）共同定义为慢性骨髓增生性肿瘤。     

细胞因子受体-JAK激酶信号通路与骨髓增殖性疾病

0引言 细胞因子受体-JAK-STAT通路是一条重要的细胞增殖信号转导通路,该通路的激活对促进细胞增殖、抑制细胞凋亡具有重要作用.上述信号通路中血小板生成素受体(MPL),JAK激酶突变的发现为真性红细胞增多症(PV)、原发性血小板增多症(ET)、原发性骨髓纤维化(IMF)等BCR/ABL融合基因阴性的骨髓增殖性疾病(MPD)的分子发病机制研究奠定了基础.研究发现JAK2V617F组成性激活活性需要Ⅰ型细胞因子受体的参与才能发挥作用.细胞冈子受体突变亦可引起某些MPD的发生,如MPLW515L.下面对细胞因子受体-JAK信号转导通路在MPD中的作用作一综述.     

JAK2 V617F基因突变阳性骨髓增殖性肿瘤治疗研究进展

JAK2 V617F基因突变阳性骨髓增殖性肿瘤(MPN)由真性红细胞增多症(PV)、原发性血小板增多症(ET)和原发性骨髓纤维化(PMF)组成.文章聚焦于其危险度积分系统和治疗进展,包括一线及二线治疗、JAK2抑制剂、降细胞治疗、抗纤维化和其他单药或联合治疗.     

原发性血小板增多症、真性红细胞增多症转变白血病二例

原发性血小板增多症(PT)、真性红细胞增多症(PV)、骨髓纤维化(MF)、慢性粒细胞白血病(CML)属于骨髓增生性疾病。这些疾病可以互相转化,我院诊治2例患者,追踪观察,其中1例长达28年,现将其疾病演变过程报道如下。例1男,39岁,教师。1974年春开始出现头晕、周身无力、肢体麻木,同年     

A myeloproliferative disorder may hide another one

Chronic myeloproliferative disorders (MPDs) are divided into Philadelphia-positive chronic myeloid leukemia (CML) and Philadelphia-negative disorders including polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis (IMF). Concomitance of a CML and another MPD is a rare event. We report here the case of a patient presenting initially with IMF who developed a Philadelphia-positive CML 7 years later. At the time of CML diagnosis, two distinct clones were present, one with a 13q deletion and one with a t(9;22). We raise the problem of a CML developing on an initial IMF, or two MPDs occurring from a common or two different stem cells.     

骨髓增殖性肿瘤研究进展:JAK2 V617F基因突变发现后10年

结合大量的临床实践和近10年来对骨髓增殖性肿瘤(MPN)[骨髓增殖性疾病(MPD)]在JAK2 V617F基因突变等分子水平的大量研究,更加深了对MPN(MPD)的分子发病机制和临床价值的认识.研究者们探讨了JAK2 V617F基因突变如何促进MPN(MPD)发病的机制,分析了JAK2 V617F基因突变的分子机制和JAK2 V617F基因突变如何引起MPN(MPD)不同临床表型,以及MPN(MPD)基因组突变图谱及其生物学意义,指出了MPN(MPD)病理克隆的复杂性.JAK2 V617F基因突变在研究和诊治MPN(MPD)的过程中发挥着重大作用,其促使MPN(MPD)的研究和应用深入到基因/分子水平,治疗更趋于靶向性,更加精确,特别是使那些常规检验无法明确诊断的患者获得了及时诊治,避免了合并疾病的发生.MPN(MPD)的防治焦点是及时诊治,预防并避免血栓/出血性并发症的发生.推荐首选干扰素α(IFN-α)治疗,对于年龄大于60岁的患者,羟基脲是可以采用的.MPN(MPD)患者的预后大多数良好,发生恶变的风险不高,这是反复建议对中国MPD患者避免使用MPN称谓的主要理由.     

BCR-ABL-negative myeloproliferative Neoplasien

BCR-ABL negative myeloproliferative neoplasms are a heterogeneous group of disorders characterized by a proliferation of one or more myeloid cell lineages. The most common entities are polycythemia vera, essential thrombocythemia and myelofibrosis in which Janus kinase (JAK) and myeloproliferative leukemia virus oncogene (MPL) mutations are found in 60?C70% of patients resulting in constitutive activation of the JAK-STAT signal transduction pathway. The clinical and morphological characteristics in peripheral blood and bone marrow are nowadays regularly complemented by cytogenetic and molecular analyses. Precise diagnostic criteria and prognostic markers allow a reliable evaluation of the therapeutic options. Effective targeted therapies have now been developed against pathogenetic signaling pathways, e.g. JAK inhibitors, which in the future will possibly be used as monotherapy or in combination with or without subsequent allogeneic stem cell transplantation.     

Advances in the molecular characterization of Philadelphia-negative chronic myeloproliferative disorders

PURPOSE OF REVIEW: The identification and characterization of somatic disease alleles have greatly improved our understanding of the molecular pathogenesis of myeloproliferative disorders. This review focuses on recent studies investigating the role of activated tyrosine kinase signaling in the Philadelphia chromosome negative myeloproliferative disorders. RECENT FINDINGS: Previously identified tyrosine kinase mutations in chronic myeloid leukemia and other myeloproliferative disorders suggested the possibility that polycythemia vera, essential thrombocythemia and primary myelofibrosis are also caused by activated tyrosine kinases. Recent studies identified an activating mutation in the JAK2 tyrosine kinase (JAK2V617F) in most patients with polycythemia vera and in approximately half of those with essential thrombocythemia and primary myelofibrosis. More recently, activating mutations in the thrombopoietin receptor and in JAK2 exon 12 have been identified in JAK2V617F negative myeloproliferative disorders. SUMMARY: The discovery of activated tyrosine kinases in the majority of patients with polycythemia vera, essential thrombocythemia and primary myelofibrosis has diagnostic and pathogenetic implications. Subsequent studies are needed to elucidate the cause of myeloproliferative disorders without known disease alleles and to determine if inhibition of JAK2 signaling has therapeutic efficacy in the treatment of polycythemia vera, essential thrombocythemia and primary myelofibrosis.     

JAK2基因突变与骨髓增生性疾病的关系

 骨髓增生性疾病（MPD）中真性红细胞增多症（PV）、特发性血小板增多症（ET）、特发性骨髓纤维化（IMF）发现蛋白酪氨酸激酶（JAK2）基因上有一个碱基突变JAK2 V617F,突变明显与PV、ET和IMF的发生有关,这一发现可能成为诊断这类综合征的一种方式,也为寻找新的药物治疗MPD提供了明确的作用目标,同时还为研究细胞生长紊乱和细胞功能紊乱提供新的研究思路。     

Transformation of a Chronic Myeloproliferative Neoplasm to Acute Myelogenous Leukemia: Does Anything Work?

The BCR/ABL-negative myeloproliferative neoplasms (MPNs) of essential thrombocythemia, polycythemia vera, and primary myelofibrosis, over the natural course of their disease, have an increasing predisposition to transform to overt acute myeloid leukemia (AML)—most appropriately referred to as MPN-blast phase (MPN-BP). Although this transformation is a rare event, once AML has occurred, it is associated with a poor response to therapy and short survival. The molecular events leading to transformation are poorly defined. Currently, no therapy other than allogeneic stem cell transplantation (ASCT) has been demonstrated to alter the natural history of this disease. Multiple therapeutic investigations are currently ongoing, including early ASCT, hypomethylating agents, and JAK2 inhibition, to try to alter the course of the disease and improve outcomes. This review focuses on the latest advances in our understanding of the biology of leukemic transformation and current clinical therapies that are available for this patient population.     

Life expectancy of patients with chronic nonleukemic myeloproliferative disorders

This study determines, within the frame of current therapeutic possibilities, the impact of chronic nonleukemic myeloproliferative disorders on expected survival. The survival data for 1067 patients (454 with polycythemia vera, 247 with essential thrombocythemia, and 366 with idiopathic myelofibrosis) were collected from 38 Spanish institutions. The actuarial survival probability of each group of patients was compared with that of the age-matched and sex-matched control population. The survival of the patients with polycythemia vera and essential thrombocythemia did not differ from that of the control population (P = 0.92 and, 0.22, respectively), whereas the survival of the patients with idiopathic myelofibrosis was strikingly reduced with respect to the control population (P = 0.0000000007). Thus, in terms of survival, current therapeutic procedures may be considered as quite satisfactory in patients with polycythemia vera and essential thrombocythemia. On the other hand, due to poor survival of patients with idiopathic myelofibrosis, new therapeutic approaches for this condition are clearly needed.