伴有PDGFRβ基因异常的骨髓增生异常/增殖性肿瘤综合征的临床和实验研究

目的 探讨伴有血小板衍生生长因子β(PDGFRβ)基因异常的骨髓增生异常/增殖性肿瘤(MDS/MPN)综合征的临床和实验室特征.方法 按常规方法制备骨髓细胞染色体标本,用RHG显带技术进行核型分析;分别应用PDGFRβ、PDGFRα、FGFR1分离探针,5号、12号全染色体涂抹探针,进行双色荧光原位杂交(D-FISH)和染色体涂抹分析;定量PCR方法检测JAK2 V617F基因.结果 27例患者临床和血液学改变符合MDS/MPN综合征诊断,用D-FISH技术从中筛查出4例患者伴有PDGFRβ基因的重排,其中2例用涂染技术证实为t(5;12).4例PDGFRβ阳性的MDS/MPN患者均未检测到PDGFRα、FGFR1、JAK2 V617F基因异常.结论 PDGFRβ重排可见于部分MDS/MPN患者.这类疾病应被归入"伴有PDGFRβ异常的髓系肿瘤"的范畴,嗜酸粒细胞增高并不是它们的共同临床表现,用FISH技术筛查PDGFRβ基因是一种简便、可靠的检测手段,对于提高诊断水平及指导临床用药具有重要意义.     

FGFR1基因异常在血液肿瘤中的临床意义

目的:研究血液系统肿瘤中成纤维细胞生长因子受体1(FGFR1)基因异常对疾病诊断、临床特征、病理机制及治疗选择的指导意义及临床应用。方法:收集我院2013年至2018年带有8号染色体短臂(8P)异常且病史资料较为全面的患者共29例,运用染色体R带显带技术对患者骨髓染色体进行核型分析,并运用荧光原位杂交技术(FISH)进行FGFR1基因检测。结果:FISH检测出FGFR1基因异常患者共7例,其中FGFR1基因扩增患者3例、易位改变患者2例、缺失患者2例。FGFR1基因扩增或缺失的5例患者均不伴有嗜酸性粒细胞增高,且染色体为复杂核型,预后较差;2例FGFR1基因易位病例为非复杂染色体易位,其中1例经骨髓移植后6年仍存活,另1例染色体核型分析8号短臂未见重排,但通过FISH检测证实了FGFR1基因的重排且为罕见的插入性易位。结论:FGFR1基因扩增或缺失病例多发生在复杂核型中,不伴有嗜酸性粒细胞升高,预后差。FGFR1基因易位患者伴有嗜酸细胞增多,符合伴FGFR1异常的髓系/淋系肿瘤的临床特征。染色体核型分析和FISH方法相结合可以提高异常克隆的检出。     

骨髓增生异常综合征转为急性嗜酸粒细胞白血病1例并文献复习

目的观察急性嗜酸粒细胞白血病(AEL)的形态特征、遗传特征、免疫表型及分子标记特征以提高对AEL的认识。方法对我院收治的1例难治性血细胞减少伴多系发育异常(MDS-RCMD)转为AEL患者的病历资料进行回顾性总结并复习相关文献。结果该例MDS-RCMD患者12个月后转为AEL;骨髓原始细胞占10.4%,嗜酸粒细胞占70.8%,其中嗜酸性早、中、晚幼粒细胞占69.6%;外周血嗜酸粒细胞占13.5%;骨髓原始细胞伴有复杂染色体异常、CD34、CD117、HLD-DR、CD33、CD38、CD13等阳性表达;FI1L1/PDGFRα和ETV6/PDGFRα融合基因阴性。按AML治疗2个月后患者死亡。结论该例AEL患者FI1L1/PDGFRα和ETV6/PDGFRα基因重排阴性,伊马替尼治疗无效。     

胸腺瘤48例临床病理的预后相关性研究

Objective To study the relation of Clinicopathological characteristics and prognostic of thy-mic epithelial tumors. Methods To review and analyze the clinical data about 48 cases with thymic epithelial tumours were treated in surgery of our hospital,, according to the normal sort of WHO (2004 years) thymus tumor classification criteria to classify, according to the results of the clinical and follow-up and Masaoka clinical stage and prognosis, and other factors The relevance of the study. Results 48 cases of histological type of thymoma: A type for 4 cases(8.3%) ,AB type for 3(6.3%) ,B1 type for 9(18.8%) ,B2 type for 8(16.7%) ,B3 type for 11 cases(22.9% ) ,C type for 13 cases(27.1% ). Clinical staging: Ⅰ period of 12 cases(25.0% ), Ⅱ period of4 cases( 8.3% ), Ⅲ period of 13 cases(27.1% ), Ⅳ period of 19 cases(39. 6 percent). The results of follow-up data show that, Ⅰ,Ⅱ,Ⅲ,Ⅳ Thymectomy period after 3-year survival rates were 100% and 100% ,68.3%, 35.8% ;5-year survival rates were 66.5% and 66.5% ,39.7%, 18.6% and the survival rate of patients with Masaoka closely related to the clinical stage, patients with thymoma is the most important independent prognostic indicators. Conclusion Masaoka's clinical stage of survival in patients with thymoma is the most important prognostic parameters,type of tumor is complete excision is the impact on the survival of patients with thymoma an important factor.     

嗜酸性粒细胞增多患者的细胞遗传学和分子生物学特征的研究

本研究旨在探讨嗜酸性粒细胞增多患者的细胞遗传学和分子生物学特征。通过间期荧光原位杂交(FISH)和逆转录聚合酶链式反应(RT-PCR)的方法对79例嗜酸性粒细胞增多(嗜酸性粒细胞计数≥1.5×109/L)患者的PDGFRA/B和FGFR1基因重排进行检测,并对44例患者的T细胞受体(TCR)基因重排进行了检测。结果显示:79例患者中检出FIP1L1/PDGFRA(F/P)融合基因阳性19例,检出CHIC2缺失19例,检出PDGFRB基因重排4例,未检测到FGFR1基因重排患者。按照2008年WHO分类修订诊断后,有42%(20/48)的高嗜酸性粒细胞综合征(HES)和83%(5/6)的慢性嗜酸性粒细胞白血病(CEL)患者更正诊断为伴PDGFRA/B重排的髓系肿瘤,17%(1/6)的CEL更正诊断为慢性嗜酸性粒细胞白血病,非特指型(CEL-NOS)。染色体核型分析检出克隆性细胞遗传学异常4例,1例为CEL-NOS,3例为伴PDGFRB重排的髓系肿瘤,所有21例伴PDGFRA重排的患者均未检测出4q12异常。伴PDGFRA/B重排的髓系肿瘤、HES和继发性嗜酸性粒细胞增多3组患者的克隆性TCR基因重排检出率分别为33%(5/15)、40%(6/15)和36%(5/14),3组间无明显差异。结论:在既往诊断HES和CEL的患者中存在较高比例的PDGFRA/B基因重排,通过间期FISH和PCR方法可以提高伴PDGFRA/B重排的髓系肿瘤的诊断。     

胸腺瘤48例临床病理的预后相关性研究

Objective To study the relation of Clinicopathological characteristics and prognostic of thy-mic epithelial tumors. Methods To review and analyze the clinical data about 48 cases with thymic epithelial tumours were treated in surgery of our hospital,, according to the normal sort of WHO (2004 years) thymus tumor classification criteria to classify, according to the results of the clinical and follow-up and Masaoka clinical stage and prognosis, and other factors The relevance of the study. Results 48 cases of histological type of thymoma: A type for 4 cases(8.3%) ,AB type for 3(6.3%) ,B1 type for 9(18.8%) ,B2 type for 8(16.7%) ,B3 type for 11 cases(22.9% ) ,C type for 13 cases(27.1% ). Clinical staging: Ⅰ period of 12 cases(25.0% ), Ⅱ period of4 cases( 8.3% ), Ⅲ period of 13 cases(27.1% ), Ⅳ period of 19 cases(39. 6 percent). The results of follow-up data show that, Ⅰ,Ⅱ,Ⅲ,Ⅳ Thymectomy period after 3-year survival rates were 100% and 100% ,68.3%, 35.8% ;5-year survival rates were 66.5% and 66.5% ,39.7%, 18.6% and the survival rate of patients with Masaoka closely related to the clinical stage, patients with thymoma is the most important independent prognostic indicators. Conclusion Masaoka's clinical stage of survival in patients with thymoma is the most important prognostic parameters,type of tumor is complete excision is the impact on the survival of patients with thymoma an important factor.     

胸腺瘤48例临床病理的预后相关性研究

Objective To study the relation of Clinicopathological characteristics and prognostic of thy-mic epithelial tumors. Methods To review and analyze the clinical data about 48 cases with thymic epithelial tumours were treated in surgery of our hospital,, according to the normal sort of WHO (2004 years) thymus tumor classification criteria to classify, according to the results of the clinical and follow-up and Masaoka clinical stage and prognosis, and other factors The relevance of the study. Results 48 cases of histological type of thymoma: A type for 4 cases(8.3%) ,AB type for 3(6.3%) ,B1 type for 9(18.8%) ,B2 type for 8(16.7%) ,B3 type for 11 cases(22.9% ) ,C type for 13 cases(27.1% ). Clinical staging: Ⅰ period of 12 cases(25.0% ), Ⅱ period of4 cases( 8.3% ), Ⅲ period of 13 cases(27.1% ), Ⅳ period of 19 cases(39. 6 percent). The results of follow-up data show that, Ⅰ,Ⅱ,Ⅲ,Ⅳ Thymectomy period after 3-year survival rates were 100% and 100% ,68.3%, 35.8% ;5-year survival rates were 66.5% and 66.5% ,39.7%, 18.6% and the survival rate of patients with Masaoka closely related to the clinical stage, patients with thymoma is the most important independent prognostic indicators. Conclusion Masaoka's clinical stage of survival in patients with thymoma is the most important prognostic parameters,type of tumor is complete excision is the impact on the survival of patients with thymoma an important factor.     

经后路椎间盘镜手术患者的综合康复护理探讨

Objective To study the clinical effect of comprehensive rehabilitation nursing of postopera-tive patients treated by micrecndoscopic discectomy through posterior approach. Methods Fifty - four patients with Inmhar disc herniation were performed to remove nucleus pulposus with microendoscopic discectomy. A retro-spective analysis of 51 patients was made, and the therapeutic effect of the comprehensive rehabilitation nursing was evaluated. Results After operation, the patients could walk in 2±1 days, resumed their daily activities in 11±5 days and went back to work in 28±9 days. Excellent results were achieved in cases 44 (86.3% ), good in cases 3 (5.9%) and improved in cases 4 (7. 8% ) according to the Nakni scale. The excellent and good results were 92.2%. Conclusions Comprehensive rehabilitation nursing is effective in the postoperative patients treated by micrcendoscopic discectomy through posterior approach.     

伴两个t(15;17)易位的四倍体核型急性早幼粒细胞性白血病的实验和临床研究

目的 探讨伴有2个t(15;17)易位的四倍体核型APL的临床和实验室特点.方法 选取5例伴有2个t(15;17)易位为特征的四倍体核型APL病例,采用骨髓细胞直接法或短期培养法制备染色体,用R显带技术进行核型分析;采用流式细胞术对1例患者进行DNA倍性分析,检测APL患者白血病细胞表面CD2、CD13、CD15、CD33和CD34的表达;采用PML/RARα双色探针和FISH技术,检测其中1例APL患者的PML/RARα融合基因;采用RT-PCR技术,检测2例APL患者的PML/RARα融合基因的转录本.结果 5例APL患者均为男性,中位年龄38岁.骨髓细胞形态学检查显示,骨髓早幼粒细胞胞体巨大、胞核畸形.R显带染色体分析显示,5例APL患者均有以2个t(15;17)(q22;q12)为特征的四倍体或近四倍体核型细胞,其中1例同时伴有t(15;17)二倍体核型细胞和1个正常细胞,2例同时伴有正常核型的细胞.5例APL患者中,1例经间期FISH检测证实,含有2个PML/RARα融合荧光信号;2例经RT-PCR检测证实PML/RARα融合基因阳性.5例APL患者中,1例患者的白血病细胞仪表达CD33;其余4例表达CD13和CD33,其中2例同时表达CD2,1例同时表达CD34.采用流式细胞术对1例患者进行DNA倍体分析,发现四倍体克隆峰,其DNA指数为1.998,变异系数为8.2%.全部病例经全反式维甲酸和(或)砷剂治疗后均获得完全缓解.结论 伴2个t(15;17)易位的四倍体APL患者的骨髓涂片中均可见到巨大畸形白血病细胞;此类患者多为短型PML/RARα转录本;此类核型异常并不影响全反式维甲酸的疗效及预后.     

Assessing the activity of cediranib, a VEGFR-2/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family

Cediranib is a potent inhibitor of the VEGF receptor (VEGFR)-2 and VEGFR-3 tyrosine kinases. This study assessed the activity of cediranib against the VEGFR-1 tyrosine kinase and the platelet-derived growth factor receptor (PDGFR)-associated kinases c-Kit, PDGFR-α, and PDGFR-β. Cediranib inhibited VEGF-A-stimulated VEGFR-1 activation in AG1-G1-Flt1 cells (IC(50) = 1.2 nmol/L). VEGF-A induced greatest phosphorylation of VEGFR-1 at tyrosine residues Y1048 and Y1053; this was reversed by cediranib. Potency against VEGFR-1 was comparable with that previously observed versus VEGFR-2 and VEGFR-3. Cediranib also showed significant activity against wild-type c-Kit in cellular phosphorylation assays (IC(50) = 1-3 nmol/L) and in a stem cell factor-induced proliferation assay (IC(50) = 13 nmol/L). Furthermore, phosphorylation of wild-type c-Kit in NCI-H526 tumor xenografts was reduced markedly following oral administration of cediranib (≥1.5 mg/kg/d) to tumor-bearing nude mice. The activity of cediranib against PDGFR-β and PDGFR-α was studied in tumor cell lines, vascular smooth muscle cells (VSMC), and a fibroblast line using PDGF-AA and PDGF-BB ligands. Both receptor phosphorylation (IC(50) = 12-32 nmol/L) and PDGF-BB-stimulated cellular proliferation (IC(50) = 32 nmol/L in human VSMCs; 64 nmol/L in osteosarcoma cells) were inhibited. In vivo, ligand-induced PDGFR-β phosphorylation in murine lung tissue was inhibited by 55% following treatment with cediranib at 6 mg/kg but not at 3 mg/kg or less. In contrast, in C6 rat glial tumor xenografts in mice, ligand-induced phosphorylation of both PDGFR-α and PDGFR-β was reduced by 46% to 61% with 0.75 mg/kg cediranib. Additional selectivity was showed versus Flt-3, CSF-1R, EGFR, FGFR1, and FGFR4. Collectively, these data indicate that cediranib is a potent pan-VEGFR kinase inhibitor with similar activity against c-Kit but is significantly less potent than PDGFR-α and PDGFR-β.     

Current diagnosis of myeloproliferative neoplasms (2008 WHO classification)

The paper discusses the new 2008 WHO classification of myeloproliferative neoplasms (MPN) and compares it with its previous 2001 edition. The introduction of the last version of the WHO classification into clinical practice has been due to new molecular biological and histological evidence in patients with MPN. The classification contains substantial alterations made in a number of nosological entities and the new diagnostic marker for MPN - JAK2 gene mutation being proposed. Mastocytosis-specific c-KIT anomaly is identified. A new form of hematopoietic system tumors, such as myeloid and lymphoid neoplasias with eosinophilia and mutations of the PDGFR A and B and FGFR1 genes, is singled out and characterized. New differential diagnostic parameters of a histological study of bone marrow trepans in MPN are proposed.     

Myeloid neoplasm with eosinophilia and rearrangement of platelet-derived growth factor receptor beta gene in children: Two case reports

BACKGROUNDMyeloid neoplasm (MN) with eosinophilia and rearrangement of platelet-derived growth factor receptor beta (PDGFRB) shows a good therapeutic response to imatinib in adults. MN is rarely found in children, and the efficacy of imatinib on pediatric patients remain unclear.CASE SUMMARYWe report 2 pediatric cases diagnosed with MN with eosinophilia and PDGFRB rearrangement who were treated with imatinib. Case 1 was a 1-year-old girl admitted to the hospital because of “abdominal distension with hyperleukocytosis for 3 mo”. She had leukocytosis, anemia, and eosinophilia (the absolute eosinophil count (AEC) was 8960/μL), and her fluorescence in situ hybridization (FISH) test revealed that PDGFRB rearrangement was detected in 70% of 500 interphase cells. Case 2 was a 2-year-old girl admitted to the hospital because of “recurrent fever and rashes for 1 mo”. Her blood cell count showed an AEC of 3540/μL. The FISH test revealed that PDGFRB rearrangement was detected in 71% of 500 interphase cells. Both patients were diagnosed as MN with eosinophilia and PDGFRB rearrangement. Imatinib was added into their treatment regimen. As expected, complete hematologic remission was achieved after 1 mo of treatment, and symptoms disappeared.CONCLUSIONAlthough MN with eosinophilia and PDGFRB rearrangement usually occurs in adults, it can be found in children. The therapeutic benefits of imatinib in these 2 pediatric patients were consistent with its reported effects in adult patients.     

间期荧光原位杂交技术检测恶性血液病的11q23/MLL基因重排

目的分析伴有11q23／MLL基因重排的恶性血液病的细胞遗传学特点，探讨荧光原位杂交技术（FISH）在诊断及鉴定恶性血液病11q23／MLL基因重排中的价值。方法用间期FISH分析11q23／MLL基因易位细胞的30例恶性血液病患者的核型特征，用MLL双色分离探针绿色标记在（5′MLL，光谱绿）和（3′MLL，光谱桔红）。结果应用常规细胞遗传学及间期FISH分析白血病患者30例，结果显示11q23＋／MLL＋患者9例（30．0％），12q23-／MLL＋患者4例（13．3％），11q23＋／MLL-患者2例（6．7％），11q23-／MLL-患者15例，检测到部分病例染色体核型分析与间期FISH方法检测11q23异常与MLL基因重排不一致。结论FISH在检测11q23／MLL基因重排方面与传统的常规细胞遗传学相比具有检出率高的优势，能更有效、直观地分析恶性血液病的染色体异常，对于恶性血液病的诊断以及异常染色体的检出具有广泛的应用前景。     

PML/RARα融合基因不典型FISH信号模式的APL的实验与临床特征研究

目的：探讨伴有PML/RARα不典型FISH信号模式的急性早幼粒细胞白血病的临床和实验室特征。方法采用PML/RARα的DCDF-FISH技术、染色体核型分析及FLT3-ITD突变检测技术对初诊的52例急性早幼粒细胞白血病患者骨髓标本进行检测,比较FISH信号模式与其他检测结果的关系。结果在检测的52例标本中,51例存在PML/RARα融合基因,阳性率高达98.1%;51例FISH阳性患者中38例为典型的1R1G2F信号,13例呈不典型信号模式,其中2例为1R1G1F,3例为1R1G3F,6例为2R2G1F,1例为1R2G1F,1例为2R1G1F。将不典型FISH信号模式组和典型FISH信号模式组进行比较,我们发现不典型组的高白患者比率较典型组高（P〉0.05）;且不典型FISH信号模式组中复杂核型与FLT3-ITD突变的发生率明显高于典型信号组（P〈0.05）。结论具有不典型FISH信号模式的APL患者常伴有复杂核型,FLT3-ITD突变等预后不良的指标,其具体作用方式仍有待进一步探讨。     

伴嗜酸性粒细胞增多的儿童寄生虫病与结核病的临床特点分析

目的探讨四川及周边地区伴嗜酸性粒细胞增多的寄生虫病与结核病患儿的临床特点。方法回顾性分析2012~2019年我院收治的伴外周血嗜酸性粒细胞增多的寄生虫病与结核病住院患儿的临床资料。结果共收集寄生虫病患儿146例,结核病患儿21例,两者年龄、性别及地区分布特点相似,临床表现均缺乏特异性。寄生虫病组嗜酸性粒细胞百分比高于结核病组(P<0.05);两组嗜酸性粒细胞绝对值差异无统计学意义(P>0.05)。两组患儿胸部CT结果均以斑片影、条索影、结片或结节影、肺门或纵膈淋巴结增大、胸膜增厚多见。寄生虫病组中胸腔积液和心包积液的嗜酸性粒细胞百分比中位数均为86%;结核病组中2例胸腔积液和2例腹腔积液的嗜酸性粒细胞百分比分别为3%、22%、20%及25%。结论伴嗜酸性粒细胞增多的儿童寄生虫病与结核病的临床特点相似,不易区分;但两类患儿的外周血嗜酸性粒细胞百分比有明显差异,且寄生虫病患儿浆膜腔积液以嗜酸性粒细胞增高为主,结核病患儿嗜酸性性粒细胞增高不明显,可辅助临床医师鉴别。     

SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and INK4A/ARF aberrations in mice and humans

Recent collaborative efforts have subclassified malignant glioblastomas into 4 clinical relevant subtypes based on their signature genetic lesions. Platelet-derived growth factor receptor α (PDGFRA) overexpression is concomitant with a loss of cyclin-dependent kinase inhibitor 2A (CDKN2A) locus (encoding P16INK4A and P14ARF) in a large number of tumors within one subtype of glioblastomas. Here we report that activation of PDGFRα conferred tumorigenicity to Ink4a/Arf-deficient mouse astrocytes and human glioma cells in the brain. Restoration of p16INK4a but not p19ARF suppressed PDGFRα-promoted glioma formation. Mechanistically, abrogation of signaling modules in PDGFRα that lost capacity to bind to SHP-2 or PI3K significantly diminished PDGFRα-promoted tumorigenesis. Furthermore, inhibition of SHP-2 by shRNAs or pharmacological inhibitors disrupted the interaction of PI3K with PDGFRα, suppressed downstream AKT/mTOR activation, and impaired tumorigenesis of Ink4a/Arf-null cells, whereas expression of an activated PI3K mutant rescued the effect of SHP-2 inhibition on tumorigenicity. PDGFRα and PDGF-A are coexpressed in clinical glioblastoma specimens, and such co-expression is linked with activation of SHP-2/AKT/mTOR signaling. Together, our data suggest that in glioblastomas with Ink4a/Arf deficiency, overexpressed PDGFRα promotes tumorigenesis through the PI3K/AKT/mTOR-mediated pathway regulated by SHP-2 activity. These findings functionally validate the genomic analysis of glioblastomas and identify SHP-2 as a potential target for treatment of glioblastomas.