目的 明确亚甲基四氢叶酸还原酶（MTHFR）C677T、A1298C基因多态性与成人患者使用大剂量甲氨蝶呤（MTX）治疗急性淋巴细胞白血病（ALL）毒性反应和24、48、72 h MTX血药浓度关系。方法 收集2014年6月—2020年6月就诊于新疆医科大学第一附属医院成人急性淋巴细胞白血病75例患者血样检测MTHFR C677T及A1298C基因多态性, 根据抗癌药物常见毒性反应分级标准对毒性反应进行分级,采用非条件Logistic回归分析MTHFR C677T、A1298C基因多态性与HD-MTX毒性反应及血药浓度的关系。结果 MTHFR 677TT型发生贫血风险显著高于CC型（P=0.027, OR=4.694, 95%CI：1.195~18.438）; 未发现MTHFR C677T与白细胞减少、血小板计数减少、中性粒细胞计数减少、淋巴粒细胞计数减少、骨髓抑制、谷丙转氨酶升高、谷草转氨酶升高、肝功能损伤、急性肾损伤及黏膜损伤、24 h、48 h及72 h MTX血药浓度有相关性（P>0.05）; 未发现MTHFR A1298C与HD-MTX毒性反应及血药浓度有相关性（P>0.05）。结论 MTHFR C677T基因多态性与成人急性淋巴细胞白血病患者大剂量MTX化学治疗后血液毒性存在相关性。

Objective To determine the relationship among C677T and A1298C gene polymorphisms of methyltetrahydrofolate reductase（MTHFR）and adult acute lymphocytic leukemia（ALL）, the relationship between the toxicity of high-dose methotrexate（HD-MTX）after chemotherapy and the MTX blood concentration of 24 h, 48 h and 72 h in patients with ALL．Methods Blood samples were collected from 75 adult patients with ALL who were treated at the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2020．The samples were used to detect the genetic polymorphisms of MTHFR C677T and A1298C, and the toxic reactions were graded according to the common toxic reaction classification criteria of anti-cancer drugs．Unconditional Logistic regression was used to analyze the relationship between MTHFR C677T and A1298C gene polymorphisms and HD-MTX toxic reactions and blood drug concentration．Results The risk of anemia in MTHFR 677TT was significantly higher than that in CC type（P=0.027, OR=4.694, 95% CI：1.195-18.438）．No correlation was found between MTHFR C677T and leukopenia, thrombocytopenia, neutropenia, lymphogranulocytopenia, bone marrow suppression, elevated alanine aminotransferase, elevated aspartate aminotransferase, liver function injury, acute kidney injury and mucosal injury, 24 h, 48 h and 72 h MTX plasma concentrations（>0.05）．No correlation was found among MTHFR A1298C and HD-MTX toxicity and blood concentration（P>0.05）．Conclusions MTHFR C677T gene polymorphism is associated with hematotoxicity after HD-MTX chemotherapy in adult patients with ALL．

CCAAT增强子结合蛋白A（CEBPA）是调节血液发育过程中髓系分化和造血干祖细胞活性的关键转录因子之一。CEBPA基因突变常见于急性髓系白血病（AML）中,最近研究表明CEBPA bZIP框内单位点和经典双等位基因突变AML患者均具有类似的临床特征,已被单独划分为AML亚群。CEBPA bZIP框内突变而非传统的双等位CEBPA基因突变成为AML良好预后的分子指标,表明其在AML疾病进展和治疗预后中的重要性和特殊性。本文将从CEBPA蛋白在血液系统中的功能、CEBPA bZIP框内突变AML的临床特征与分子作用机制、以及伴CEBPA突变AML的治疗现状等方面进行综述,为进一步研究CEBPA bZIP框内突变在AML中的致病性和精准治疗新药物开发提供参考。

CCAAT enhancer-binding protein A（CEBPA）is one of the key transcription factors regulating myeloid differentiation and hematopoietic stem/progenitor cell maintenance during hematopoiesis．CEBPA gene mutations are commonly found in acute myeloid leukemia（AML）．Recent studies have demonstrated that AML patients haboring single CEBPA bZIP in-frame mutations or classical bi-allelic CEBPA mutations show similar clinical features and it has been individually classified as AML subgroup．Additionally,it is CEBPA bZIP in-frame mutations rather than the traditional biallelic CEBPA mutations that have emerged as a molecular indicator of favorable prognosis for clinical AML management,suggesting its importance and specificity in AML disease progression and therapeutic prognosis．Here,we reviewed serval aspects including the hematopoietic function of CEBPA protein,the clinical features and molecular mechanisms of AML with CEBPA bZIP in-frame mutations,and the current status of the treatment of AML with CEBPA mutations,which will provide a reference for further study of the pathogenicity of CEBPA bZIP in-frame mutations in AML and the development of new drugs for precision therapy．

目的 探讨重楼皂苷Ⅰ（PPI）对慢性髓系白血病细胞（K562）细胞的抑制作用及可能的作用机制。方法 采用CCK-8法筛选药物最适浓度,将培养时间为24 h的药物最适浓度作为后续实验的干预浓度。分组如下：（1）空白组;（2）PPI组;（3）抑制剂组;（4）PPI+抑制剂组。采用CCK-8法检测细胞增殖率;AO/EB染色观察细胞形态;流式细胞术检测凋亡率;ROS检测试剂盒检测活性氧（ROS）含量、还原型谷胱甘肽含量检测试剂盒检测谷胱甘肽（GSH）含量、细胞亚铁比色法测试盒检测细胞亚铁（Fe²⁺）含量;qRT-PCR法和蛋白免疫印迹法检测各组肿瘤蛋白53（p53）、钠氯离子依赖性氨基酸转运蛋白11（SLC7A11）、谷胱甘肽过氧化物酶4（GPX4）mRNA及蛋白表达量。结果 PPI抑制K562细胞的生长,且呈一定的剂量及时间依赖性（与同时间段的对照组0μmol/L比较,均P<0.01）。与空白组相比,PPI抑制K562细胞的增殖,提高了凋亡率,而铁死亡抑制剂（Ferrostian-1）的使用逆转了PPI对K562凋亡的促进作用（P<0.01）。与空白组相比,PPI组ROS、Fe²⁺含量升高,GSH含量下降,而铁死亡抑制剂的使用可下调ROS、Fe²⁺,上调GSH的含量（P<0.01）。PPI组较空白组p53 mRNA和蛋白表达水平升高,而SLC7A11、GPX4 mRNA和蛋白表达水平下降（P<0.05）;PPI+抑制剂组细胞较重楼皂苷组p53 mRNA和蛋白表达水平下降,而SLC7A11、GPX4 mRNA和蛋白表达水平升高（P<0.05）。结论 PPI能够有效抑制K562细胞增殖,促进K562细胞铁死亡,其分子机制可能与p53信号通路的调控有关。

Objective To investigate the inhibitory effect of polyphyllin I（PPI）on chronic myeloid leukemia cells（K562）and its possible mechanism．Methods K562 cell line was cultured in suitable environment,and the optimal concentration of the drug was screened by CCK-8 method．The optimal concentration of the drug cultured for 24 hours was used as the intervention concentration of the follow-up experiment．Cells were divided into the following groups：（1）blank group,（2）saponins group,（3）inhibitor group and（4）saponins + inhibitor group．The cell proliferation rate was detected by CCK-8 method．The cell morphology was observed by AO/EB staining．The apoptosis rate was detected by flow cytometry．The contents of reactive oxygen species（ROS）,glutathione（GSH）and ferrous（Fe²⁺）in different groups were detected,and the expression of mRNA and protein in different groups were detected by qRT- PCR and Western blot respectively．Results PPI significantly inhibited the growth of K562 cells in a dose-and time-dependent manner．Compared with the blank group,PPI significantly inhibited the proliferation of K562 cells and increased the apoptosis rate of K562 cells,while the use of ferroptosis inhibitor（Ferrostian-1）reversed the promoting effect of PPI on apoptosis of K562 cells．Compared with the blank group,the contents of reactive oxygen species（ROS）and ferrous iron（Fe²⁺）increased and the content of glutathione（GSH）decreased in the saponins group．The use of Ferrostian-1 could down-regulate the contents of ROS and Fe²⁺ and increase the content of GSH in the cells treated with the drug．Compared with the blank group,the expression of p53 mRNA and protein in the saponins group increased,while the expression of SLC7A11,GPX4 mRNA and protein decreased．The expression of p53 mRNA and protein in the saponins + inhibitor group was lower than that in the saponins group,while the expression levels of SLC7A11,GPX4 mRNA and protein increased．Conclusions PPI can effectively inhibit the proliferation of K562 cells and promote ferroptosis in K562 cells．The molecular mechanism can be related to the regulation of p53 signal pathway．

目的 探讨常规超声心动图联合二维斑点追踪技术评估急性白血病患儿在接受蒽环类药物治疗后产生的心脏毒性,早期检测左心功能障碍。方法 采用前瞻性非随机观察研究,选取新诊断急性淋巴细胞白血病患儿20例,分别于确诊白血病后接受蒽环类药物治疗前、接受所有蒽环类药物剂量后以及确诊白血病1年后,进行常规超声心动图和二维斑点技术监测评估心脏毒性。结果 左室流出道速度积分TVI和E、E/E’在治疗期间下降,并在诊断后1年恢复至治疗前数值。在二维斑点追踪纵向应变中,GLPS-LAX、GLPS-A2C、LV-GLPS在完成所有蒽环类药物剂量后与诊断后比较差异有统计学意义,以及诊断后1年与蒽环类药物治疗后比较差异有统计学意义。但GLPS-A4C各时间点比较差异无统计学意义。结论 常规超声心动图联合二维斑点追踪技术的纵向整体应变可早期发现白血病患儿化疗所致的左室功能障碍。

Objective To evaluate cardiotoxicity in children with acute lymphoblastic leukemia treated with anthracyclines by echocardiography combined with 2D speckle tracking imaging,and to detect left heart dysfunction early．Methods In this prospective nonrandomized study,20 children with newly diagnosed acute lymphoblastic leukemia were assessed for cardiotoxicity by echocardiography and 2D speckle tracking imaging in three periods during the treatment．Results The left ventricular outflow tract velocity integral TVI and E,E/E’ decreased during treatment,and went back to the pre-treatment value one year after diagnosis．In the longitudinal strain of 2D speckle tracking imaging,in GLPS-LAX,GLPS-A2C,LV-GLPS,there were statistical differences between treatment completed and after diagnosis,and between 1 year after diagnosis and treatment completed．However,GLPS-A4C has no statistical significance．Conclusion sThe conventional echocardiography combined with longitudinal overall strain of 2D speckle tracking imaging can comprehensively evaluate the early changes of left ventricular dysfunction caused by chemotherapy in children with leukemia．

目的 探讨慢性淋巴细胞白血病（CLL）合并第二肿瘤临床特征和预后。方法 回顾性分析2015年8月—2021年10月我院收治的58例CLL患者,其中有11例合并第二肿瘤,47例无合并第二肿瘤,分析两组病例的临床特征及其对预后的影响。结果 CLL合并第二肿瘤和无合并第二肿瘤患者在年龄、性别、白细胞计数、血红蛋白水平、淋巴细胞计数、血小板计数、乳酸脱氢酶（LDH）、β₂-微球蛋白（β₂-MG）水平、分期、单个基因缺失类型之间比较差异无统计学意义,但CLL合并第二肿瘤患者基因缺失个数较无合并第二肿瘤CLL患者组高（χ²=11.17,P=0.03）,且总生存期较短。结论 CLL合并第二肿瘤患者常伴有多个基因缺失,且预后差,当CLL患者伴有多个基因缺失时,在诊治过程中需警惕有无合并第二肿瘤。

Objective To investigate the prognosis and clinical characteristics of chronic lymphocytic leukemia（CLL）patients with second tumor．Methods A retrospective analysis was performed on 58 cases of CLL patients who were diagnosed in our hospital from August 2015 to October 2021．The clinical data of 11 CLL patients with second cancer and 47 CLL patients without second cancer were compared and analyzed．Results There were no significant differences in age,sex,white blood cell count,lymphocyte count,platelet count,the level of serum β₂-microglobulin and lactate dehydrogenase between two groups．However,in CLL patients with second cancer,the incidence of multiple genetic deletions was higher than those without second cancer（χ² =11.17,P =0.03）．The overall survival time was shorter in CLL patients with second primary cancer．Conclusions CLL patients with second tumor have a frequent multiple gene deletions and poor prognosis．Physicians should pay attention to second cancers when diagnosing the CLL patients with multiple gene deletions．

目的 通过对43种融合基因在儿童白血病中的结果分析,探讨融合基因阳性的儿童急性B淋巴细胞白血病(acute B-lymphoblastic leukemia,B-ALL)的免疫表型特征。方法 应用实时荧光探针PCR法对2016年10月—2018年12月在深圳市儿童医院就诊的初发或复发B-ALL患儿进行融合基因检测,采用多参数流式细胞术(flow cytometry,FCM)对B-ALL患者进行免疫表型检测。结果 120例B-ALL患儿融合基因筛选总阳性率为37.5%(45/127),包括TEL/AML1 27例、E2 A/PBX1 7例、BCR/ABL1 6例、MLL 4例、TLS/ERG 1例;不同年龄段白血病融合基因阳性率差异有统计学意义(P<0.01),性别分布差异无统计学意义(P>0.05)。各融合基因阳性组CD19阳性率为100%,TEL/AML1阳性表达患者普通-B-ALL表型占比最高(77.8%),干/祖细胞抗原CD34的阳性率为81.5%;E2 A/PBX1阳性表达患者以前-B-ALL表型为主,不表达已知的T系及髓系抗原;各融合基因阳性组及阴性组患儿髓系抗原阳性率比较差异有统计学意义(P<0.01),以BCR/ABL1基因表达组阳性率最高(100%)。结论 5种融合基因在患者年龄构成及免疫表型中具有一定的分布特点;B-ALL特征性免疫表型的改变可用于融合基因表达的预测,提高融合基因结果判读的准确率。

Objective To investigate the immunophenotype features of children with acute B-lymphoblastic leukemia(B-ALL) combined with fusion gene expressing after to analyze the results of the 43 fusion genes. Methods Real-time fluorescent probe PCR assay was used for the detection of fusion genes in 120 cases of children from Shenzhen Children's Hospital with B-ALL newly or recurrently diagnosed from Oct 2016 to Dec 2018. Multi-parameter flow cytometry(FCM) was used for the detection of the immunophenotype in children with B-ALL. Results Of all the 120 cases, the fusion genes were detected at positive rate of 37.5%(45/120), included TEL/AML1 27 cases, E2 A/PBX1 7 cases, BCR/ABL1 6 cases, MLL 4 cases, TLS/ERG 1 cases. The positive rate of leukemia fusion gene had statistically difference among fusion genes positive groups based on age(P<0.01). There was no statistically difference in the gender distribution(P>0.05). The expressing of CD19 was at positive rate of 100% in all of the groups. The rate of the common-B-ALL was the highest B-ALL subtype in the TEL/AML1 positive groups(77.8%). The stem /progenitor associated antigen CD34 was at positive rate of 81.5%. The pre-B-ALL was the main subtype in the E2 A/PBX1 group, which was no expression of the known T-ALL associated antigen MyAg antigen. There was statistically difference in the positive rate of MyAg expression among all of the groups(P<0.01), with the highest rate in the BCR/ABL1 group(100%). Conclusion There were certain distribution features in age composition and immunophenotype of children with B-ALL carrying five kinds of common fusion genes. The characteristic changes of the immunophenotype of B-ALL may be used to predict the expression of fusion genes and improve the accuracy of fusion genes by the supplementary role of immunophenotype analysis.

目的 随着治疗水平和疗效的不断提高,急性白血病患者的生存质量越来越受到广泛的关注,本研究旨在探讨急性白血病(AML)患者化疗后生活质量及其相关因素。方法 采用癌症患者生存质量测定量表(European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30)中文版、患者一般状况调查问卷,对268例按照AML患者治疗后1年生活质量进行调查,并将EORTC-QLQ-C30各领域评分与患者的特征进行相关性分析。结果 AML患者年龄、FAB分型、是否恢复工作、ECOG评分、婚姻状态、生存质量评分比较上,差异有统计学意义(P>0.05);不同年龄组AML患者PF、RF、EF、SF、QL、FI评分比较上,差异有统计学意义(P<0.05);不同分型AML患者患者RF、EF、SF、QL、DY、SL、FI评分比较上,差异有统计学意义(P<0.05),恢复工作的AML患者PF、RF、SF、QL评分高于未恢复工作的AML患者,恢复工作的AML患者FA、DY、FI评分则低于未恢复工作的AML患者(P<0.05),结婚AML患者PF、RF、SF、QL评分高于未结婚患者,结婚AML患者FA评分低于未结婚患者(P<0.05);逐步多元回归分析发现,年龄、分型、ECOG评分、婚姻状况与AML生存质量有关。结论 高龄、非M3型、ECOG评分高、未婚是AML生存质量差危险因素,可能作为改善AML患者生活质量预期指标。

Objective With the continuous improvement of treatment level and efficacy, the quality of life of patients with acute myeloid leukemia (AML) has attracted more and more extensive attention. This study aimed to explore the quality of life and related factors of patients with acute leukemia (AML) after chemotherapy. Methods The Chinese version of the quality of life scale for cancer patients(European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30, and the general situation questionnaire were was used to investigate quality of life for 268 AML patients one year after treatment.And then the correlation between the EORTC-QLQ-C30 scores in various fields and the characteristics of patients were analyzed. Results There were statistical differences in the scores of age, AML types, work(yes or no),ECOG scores, and marital status in patients (P<0.05).The differences of PF, RF, EF, SF, QL, FI score of AL in different age groups were statistically significant (P<0.05), The PF, RF, EF, SF, QL and FI scores of AML patients in different age groups were statistical different (P<0.05).The scores of PF, RF, SF and QL in AML patients who returned to work were higher than those in AML patients who did not returned to work,while FA, DY and FI scores were the opposite(P<0.05).The PF, RF, SF and QL scores of married AML patients were higher than those of unmarried AML patients,while FA scores were the opposite(P<0.05).Age, classification, ECOG score, marital status were found to be associated with quality of life of AML patients by stepwise multiple regression analysis (P<0.05). Conclusion Old age, non-M3 type, high ECOG score, and unmarried are risk factors for poor quality of life for AML, which may serve as expected indicators for improving the quality of life of patients with acute leukemia.

目的 比较一线伊马替尼疗效欠佳的慢性髓性白血病慢性期(CML-CP)患者,继续伊马替尼原方案或转换为尼洛替尼治疗后的疗效及安全性。方法 收集伊马替尼疗效欠佳的 45 例患者,分为伊马替尼组22例及尼洛替尼转换组23例,22例伊马替尼组患者继续接受原方案伊马替尼治疗,剂量均为400 mg qd,又将尼洛替尼转换组分为早期尼洛替尼转换组7例,晚期尼洛替尼组转换有16例。尼洛替尼转换组的23例患者接受尼洛替尼的剂量均为400 mg,q12h。所有入组患者首诊时测定 Sokal 评分,在治疗过程中随访观察定期监测血液学、细胞遗传学及分子学缓解情况(FISH 和 RQ-PCR),并对患者用药后的基本情况、临床表现及不良反应进行记录。结果 转换尼罗替尼治疗3个月时,早期尼洛替尼转换组中国际标准化 BCR-ABL1融合基因转录本水平(BCR-ABL1^IS)＜10%的患者有 5 例(71.4%),晚期尼洛替尼转换组BCR-ABL1^IS＜10%的患者有6例(37.5%),差异无统计学意义(P＞0.05)。中位观察6(3～12)个月,尼罗替尼组中有17例(73.9%)获得部分细胞遗传学反应,9例(39.1%)患者获得主要分子学反应。伊马替尼组中有9例(40.9%)获得部分细胞遗传学反应,2例(9.1%)患者获得主要分子学反应,尼洛替尼组部分细胞遗传学反应、主要分子学反应患者优于伊马替尼组(P值分别为0.027、0.020)。45例患者中达到完全细胞遗传学反应的患者与未达到完全细胞遗传学反应相比,Sokal 评分偏低(P=0.032)。结论 尼洛替尼可使伊马替尼疗效欠佳的 CML-CP 患者达到更好的疗效,因此需要及时对伊马替尼疗效欠佳的 CML-CP 患者进行评估后及时更换为尼洛替尼等二代酪氨酸激酶抑制剂。

Objective To assess the clinical efficacy and safety of original scheme or switching to nilotinib in patients with chronic myeloid leukemia in chronic phase(CML-CP)with suboptimal response of first-line imatinib. Methods 45 patients with suboptimal response of imatinib were collected and divided into 22 patients who continued to use original scheme and 23 patients who switched to nilotinib therapy. All the 22 patients of imatinib group received imatinib 400 mg once a day. And the 23 patients of nilotinib group were divided into early switch group and late switch group. Early switch group had 7 patients, late switch group had 16 patients. Both early and late switch to nilotinib group were subsequently to nilotinib 400 mg q12h. Sokal scores of all the enrolled patients were measured at the first diagnosis. Hematology, cytogenetics and molecular remission (FISH and RQ-PCR)were monitored, and the patients' basic information, clinical manifestations and adverse reactions were recorded regularly during the treatment. Results After switching to nilotinib for 3 months,there were 5 patients (71.4%)whose BCR-ABL1^IS<10% in the early nilotinib switch group, while 6 patients (37.5%)in the late nilotenib switch group.There was no statistical difference(P>0.05).With a median observation period of 6(3～12)months,there were 17 (73.9%)patients achieved partial cytogenetic response and 9 (39.1%)patients achieved major molecular response in the nilotinib group,there were 9 patients (40.9%)achieved partial cytogenetic response and 2 patients (9.1%)achieved major molecular response in the imatinib group. Patients who achieved partial cytogenetic response and major molecular response in the nilotinib group were more than those in the imatinib group (P values were 0.027 and 0.020, respectively).Sokal scores of 45 patients who had achieved complete cytogenetic response were lower than those who had achieved it (P=0.032). Conclusion Early switch to nitotinib is feasible and effective to patients who didn't have optimal response to imatinib. It is necessary to assess patients regularly in order to have the proper timing switching patients to nilotinib therapy.

目的 探讨FLT3及C-kit基因突变在急性髓细胞白血病(AML)中的临床意义。方法 回顾性分析南方医院2010年1月—2013年12月期间初诊AML患者的临床资料,PCR分析FLT3及C-kit基因突变情况。结果 248例初诊AML患者中, FLT3-ITD突变率为16.9%,TKD突变率为3.2%,C-kit8号外显子突变率为1%,17号外显子突变率为5.2%;FLT3-ITD突变更倾向发生于正常染色体核型的AML患者;FLT3突变阳性组及C-kit突变阳性组患者的外周血白细胞数高于基因突变阴性组,染色体核型正常患者的无病生存时间较阴性组缩短(P<0.05)。但是对血红蛋白、血小板及完全缓解率(CR率)并无影响(P>0.05)。结论 FLT3及C-kit突变的AML患者有较差的临床预后。

Objective This study was to investigate the prognostic value of FLT3 and C-kit gene mutations in patients with acute myeloid leukemia (AML). Methods We retrospect and analyzed the data of the 248patients with newly diagnosed AML from January 2013 to December 2010. FLT3 and C-kit gene mutations was detected by Polymerase chain reaction (PCR). Results Among these 248 subjects, the FLT3-ITD mutation rate was 16.9%, FLT3-TKD was 3.2%, C-kit 8 exon mutation rate was 1% and 17exon mutationwas 5.2%. FLT3-ITD mutation likely occurred in AML patients with normal karyotype. The patients with FLT3-ITD mutation or C-kit mutation had significantly higher PWBC and shorter DFS than patients without gene mutations (P< 0.05), but there was no significantly differences in sex, age, Hb, PLT and CR rate of the first course induction chemotherapy among groups (P>0.05). Conclusion Among patients with AML,FLT3-ITD and C-kit mutations were associated with worse prognosis.