OBJECTIVES:Since the publication of the third edition, the WHO classification of tumors of hematopoietic and lymphoid disorders has introduced the disease entity of 'myeloid/lymphoid neoplasms with eosinophilia and PDGFRB rearrangement', in which the most common chromosomal abnormality is t(5;12) (q32;p13.2), and this abnormality generates the ETV6::PDGFRB fusion gene. However, there have been patients with hematologic features and chromosomal abnormalities that are extremely similar to those carrying ETV6::PDGFRB fusion. These rare disorders harbor ETV6::ACSL6 fusion, and only sporadic cases have been reported at present.METHODS:We report a patient with chronic eosinophilic leukemia (CEL) carrying chromosome translocation t(5;12)(q32;p13.2), and we present the clinical features. In addition, we conducted a literature review to collect all reported cases and summarized the genetic and clinical profiling as well as the treatments and outcomes.RESULT:In addition to our patient, a total of 19 cases have been previously reported, including 6 variants of ETV6::ACSL6 and 3 reciprocals. We identified a novel variant of the ETV6::ACSL6 transcript in our patient, and the breakpoint was flanked by exon 2 of ETV6 and exon 2 of ACSL6. The cellular morphology features consisted of myeloproliferative neoplasm (MPN); myelodysplastic/myeloproliferative neoplasm (MDS/MPN), specifically CEL; and acute myelocytic leukemia (AML). The treatments and outcomes varied greatly depending on the type of disease, although tyrosine kinase inhibitors (TKIs) were not effective.CONCLUSION:In contrast to neoplasms with ETV6::PDGFRB fusion, myeloid neoplasms with ETV6::ACSL6 fusion have unique characteristics.

肥大细胞白血病（mast cell leukemia，MCL）是系统性肥大细胞增生症（systemic mastocytosis，SM）中罕见的一种类型。2016年的WHO造血与淋巴组织肿瘤分类将SM分为五种亚型 [1]：惰性SM（indolent SM，ISM）、冒烟型SM（smoldering SM，SSM）、SM伴血液系统肿瘤（SM with associated hematologic neoplasm，SM-AHN）、侵袭性SM（aggressive SM，ASM）和MCL。MCL病情进展快，诊断困难，而合并嗜酸性粒细胞增多又增加了MCL诊断和治疗的难度。现报告我院新近诊断的一例MCL合并嗜酸性粒细胞增多患者并对相关文献进行复习，以提高对此罕见疾病诊疗的认识。

目的 调查格林巴利综合征患者(GBS)乙肝病毒感染情况,针对乙肝病毒感染与GBS的相关性进行研究,分析探讨乙肝病毒感染是否为GBS短期预后不良的危险因素.方法 采用回顾性研究方法,选择2010年1月～2019年12月于本院神经内科住院的115例GBS患者作为研究对象,选择该科同期住院非GBS患者150例为对照组,通过检测患者乙肝五项指标,比较分析乙肝病毒感染情况以及乙肝病毒感染与GBS患者病情转归的相关性,同时还收集GBS患者自发病至入院的时间、住院时间、前驱感染史、出入院时四肢肌力情况、血液生化指标、病情转归等数据,统计分析影响GBS患者预后的危险因素.结果 GBS患者HBcAb阳性率(52.2％)高于对照组(37.3％),GBS患者HBcAb阳性组的MRC重度及预后不良患者的比例都明显高于HBcAb阴性组,具有统计学差异(P<0.05).对预后不良患者进行Longistic回归分析显示乙肝病毒感染、呼吸肌麻痹、MRC评分重度是影响GBS短期预后的独立危险因素.结论 本研究发现GBS患者乙肝病毒感染阳性率较高,乙肝病毒感染与GBS的发生及短期预后相关.

Objective:To investigate the clinical characteristics and prognosis of Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) patients with additional chromosomal abnormalities.Methods:The data of 351 CML patients with Ph-positive in the Affiliated Hospital of Qingdao University from January 2009 to January 2019 were retrospectively analyzed. The bone marrow chromosomal karyotype analysis of all patients was performed by using R-banding technique. The clinical characteristics and karyotype of Ph-positive CML patients with additional chromosomal abnormalities at initial diagnosis were summarized, and Kaplan-Meier was used to analyze the differences in overall survival (OS) of patients with different karyotypes.Results:Among 351 patients with Ph-positive CML, 32 (9.1%) cases had variant translocation. At initial diagnosis, 47 cases had additional chromosomal abnormalities including 29 cases in chronic phase accounting for 9.15% (29/317) of all patients in chronic phase, 3 cases in accelerated phase accounting for 25.00% (3/12) of all patients in accelerated phase, 15 cases in blast crisis accounting for 68.18% (15/22) of all patients in blast crisis; there was a statistically significant difference in the chromosomal abnormalities rate of all different phases ( χ2=50.799, P<0.05). Among 47 Ph-positive CML patients with additional chromosomal abnormalities, 13 patients had complex karyotypes with more than 3 additional chromosomal abnormalities, the proportion of complex karyotypes in chronic phase, accelerated phase and blast crisis was 13.79% (4/29), 33.33% (1/3) and 53.33% (8/15), respectively, and the difference was statistically significant ( χ2=9.26, P<0.05). The study showed that the most common additional chromosomal abnormalities in chronic phase were double Ph (48.28%, 14/29) and -Y (10.34%, 3/29), while the most common chromosomal abnormalities in the blast crisis were +8 (26.67%, 4/15) and double Ph (26.67%, 4/15). Kaplan-Meier survival analysis showed that at initial diagnosis the OS time of patients with additional chromosomal abnormalities was worse than that of those with the non-additional chromosomal abnormalities group ( χ2 = 61.138, P<0.05). The OS of patients with complex karyotypes for Ph - positive CML patients with additional chromosomal abnormalities at initial diagnosis was worse than that of patients with non-complex karyotypes, and the difference was significant ( χ2 = 4.945, P < 0.05). Conclusions:The additional chromosomal abnormalities is closely related to the progression of CML, and the prognosis of CML patients with additional chromosomal abnormalities is poorer than that of patients with only Ph translocation. Moreover, the more complex the additional chromosomes are, the more likely blastic changes are, and the poorer prognosis. And additional chromosomeal abnormalities during the treatment of CML patients may also lead to the progression of blastic changes.

目的 比较MCS+与COM.TEC血细胞分离机在慢性粒细胞白血病(CML)治疗中行白细胞去除术的效果.方法 选择50例CML初诊患者,在化疗的基础上,应用血细胞分离机进行白细胞去除术治疗,其中30例使用MCS+血细胞分离机(MCS+组),20例使用COM.TEC血细胞分离机(COM.TEC组).比较两组治疗前后的血常规指标(WBC、Hb、HCT、PLT),记录两组血细胞分离术相关参数(循环总量、白细胞去除量、抗凝剂用量、运行时间)以及血细胞分离术相关不良反应(低钙血症、低血容量等).结果 行白细胞去除术后,两组WBC均降至100×109/L以下,均低于治疗前(P均<0.05).MCS+组治疗后与治疗前相比,Hb、HCT、PLT均有不同程度的降低(P均<0.05);COM.TEC组治疗前后Hb、HCT、PLT比较差异无统计学意义(P均>0.05).与COM.TEC组比较,MCS+组白细胞去除量增加,运行时间缩短(P均<0.05),两组循环总量和抗凝剂用量比较差异无统计学意义(P均>0.05).MCS+组发生抗凝剂中毒1例、低血容量5例,COM.TEC组发生抗凝剂中毒3例、血流不畅1例,两组不良反应发生率比较差异无统计学意义(P>0.05).结论 MCS+和COM.TEC两种血细胞分离机均能有效去除白细胞,达到临床预期效果,MCS+血细胞分离机去除白细胞的量更多、时间短,而COM.TEC血细胞分离机对血液成分的保护作用更佳.

目的 分析2013～2019年青岛市新生儿高苯丙氨酸血症(HPA)筛查情况及基因突变情况.方法 选择2013年1月1日～2019年12月31日在青岛市具有接产资格的96家医院出生并参加HPA筛查的新生儿375697例,采集足跟血,采用串联质谱非衍生化法进行新生儿HPA筛查,应用DNA质谱基因分析技术对患儿苯丙酸羟化酶(PAH)及BH4合成代谢相关基因(PTS、GCH1)的184个突变位点进行检测.结果 参加HPA筛查的375697例新生儿中,确诊HPA 69例,PAH缺乏症64例、四氢生物蝶呤(BH4)缺乏症5例,PAH缺乏症患儿中轻度HPA 23例、轻度苯丙酮尿症(PKU)22例、经典PKU 19例.2013～2019年HPA发病率比较P均>0.05,平均发病率为1.84/万.54例HPA患儿行基因突变位点检测,其中纯合突变1例、杂合突变7例、复合杂合突变46例,存在PAH基因突变50例、BH4基因(PTS基因)突变4例.PAH基因最常见的变异位点为p.R53H(18.95％)、p.R243Q(17.89％)、p.Y356X(7.37％)、p.R241C(6.32％)、p.A434D(5.26％)、p.R111X(5.26％).结论 2013～2019年青岛市新生儿HPA平均发病率为1.84/万,PAH基因最常见的变异位点为p.R53H、p.R243Q,并存在等位基因异质性.

目的 观察瓜氨酸血症I型(CTLN1)患者的基因突变情况,探讨其遗传学特性.方法 采用高通量测序、多重连接探针扩增技术、Sanger测序技术对1例CTLN1患儿进行氨基酸代谢障碍相关基因检测,采用Sanger测序技术对检测出的突变位点进行父母来源验证,利用SIFT软件和Polyphen-2软件对新发现的基因突变位点进行功能预测.结果 患儿ASS1基因发生复合杂合突变,两个突变位点为c.470 G>A(p.R157H)和c.577 G>A(p.G193R),其中c.470 G>A(p.R157H)突变遗传自表型正常的母亲,c.577 G>A(p.G193R)突变遗传自表型正常的父亲.c.577 G>A(p.G193R)突变在千人基因组数据库和SNP数据库中未检索到,检索PubMed数据库和ExAC数据库未发现相关致病性的报道,SIFT软件预测其为有害突变,Polyphen-2软件预测其很可能为致病突变.结论 CTLN1患者存在ASS1基因突变,且为复合杂合突变,遗传自父母.ASS1基因c.577 G>A(p.G193R)突变系新发现的突变位点.

目的 探讨急性髓系白血病(AML)病人染色体核型异常分布情况及其预后判断的临床意义.方法 应用R显带染色体分析技术,对初诊的273例AML病人进行染色体检查,分析染色体异常与AML类型及预后的关系.结果 AML病人异常染色体检出率为57.5％ (157/273),其中由骨髓增生异常综合征(MDS)转化为AML者其异常染色体检出率为66.7％(6/9). AML染色体核型预后良好组、预后不良组和预后中间组的白血病缓解率比较,差异有统计学意义(x2=16.93,P＜0.01).结论 染色体核型分析在AML病人的诊断、分型、治疗及预后判断方面均起重要作用.

Objective To explore the relationship between PAH-DNA adducts and CYP1A1,GSTM1 gene polymorphisms and lymphoma.Methods PAH-DNA adducts from bone marrow of lymphoma patients and control cases were determined by competitive ELISA.The genotypes of both CYP1A1 and GSTM1 were detected by PCR-based restriction fragment length polymorphisms (PCR-RELP).Results The level of PAH-DNA adducts in lymphoma patients [(2 498±1 250) pg/ml] was significantly higher than that in control [(1 882±797) pg/ml] (t =0.006,P ＜ 0.05).CYP1A1 mutant genotype and GSTM1 null genotype had increased risk of lymphoma,with OR being 1.36 (95 ％ CI 0.56-3.31,P ＞ 0.05),4.03 (95 ％ CI 1.51-10.76,P ＜ 0.05),respectively.GSTM1 null genotype individuals with PAH-DNA level higher (or equal) than 2 200 pg/ml had increased risk of lymphoma.Conclusions The content of PAH-DNA adducts and the occurrence of lymphoma may have a certain correlation.GSTM1 null genotype may be linked to lymphoma and increase the risk.

Objective To investigate the characteristics of chromosome abnormalities in adult acute leukemia(AL) patients and the distribution of subtypes of karyotype changes.Methods All the 285 cases of adult patients with AL received bone marrow or peripheral blood chromosome detection to analyze the relationship between chromosome abnormality and leukemia type by using R banding conventional chromosome analysis technology.Results The abnormal chromosome detection rate of AL adult patients was 56.4% in average.The rates of chromosomal abnormalities in patients with acute leukemia karyotype in acute myelocytic leukemia(AML) and acute lymphocytic leukemia(ALL) were 55.6 %(123/221) and 58.8%(30 /51) respectively.The rate of chromosomal abnormalities from MDS into AML was 57.7%(4 /7),and into lymphosarcoma leukemia was 66.7%(4 /6).In the chromosomal abnormalities,M3 was more consistent in chromosomal change,accounting for t(15;17)(q22;q11) changes in the main;t(9;22) was the most common change in ALL patients;while the other types of leukemia chromosome abnormality was not consistent.Both AML and ALL groups,the difference rate in poor prognosis group,intermediate group and good prognosis of leukemia remission was statistically significant(P < 0.01).Conclusion Karyotype analysis is helpful for the diagnosis,treatment and prognosis of leukemia.

Objective To explore the expression of nm23 and its significance in malignant lymphoma and in serum.Methods By applying immunohistochemical and ELISA method,the expression of nm23 in lymphoma tissue and in serum was detected,the correlation between the expression and clinicopathological characteristics was analyzed.Results The expression of nm23 in lymphoma and serum was obviously higher than that in the control group(χ2=9.49,t=7.21,P<0.01).The expression of nm23 was not associated with the sex of the patient,but correlated with the patient age,the degree of malignancy,clinical stage,with or without bone marrow infiltration,B symptoms and LDH level(χ2=8.86-15.25;t=3.03-9.48;P<0.01).ConclusionThe expression level of nm23 can reflect the extent of malignancy of lymphoma.

目的运用细胞遗传学方法，对本院125例慢性粒细胞性白血病(CML)惠者进行分析，探讨CML中Ph染色体的有关特点及临床意义。方法 采用24h短期培养法制备骨髓染色体，R显带技术进行染色体核型分析。结果 125例CML患者中有118例Ph+(占94%)，7例Ph-(占6%)；在Ph+病例中，具有典型易位者95例(占81%)，变异易位和涉及其他染色体异常的有23例(占19%)，其中11例为慢性期，3例为加速期，9例为急变期。结论 染色体核型分析对慢粒的诊断、鉴别诊断和预后判断具有重要的价值