Three New Ranidae Mitogenomes and the Evolution of Mitochondrial Gene Rearrangements among Ranidae Species

Various types of gene rearrangements have been discovered in the mitogenoes of the frog family Ranidae. In this study, we determined the complete mitogenome sequence of three Rana frogs. By combining the available mitogenomic data sets from GenBank, we evaluated the phylogenetic relationships of Ranidae at the mitogenome level and analyzed mitogenome rearrangement cases within Ranidae. The three frogs shared an identical mitogenome organization that was extremely similar to the typical Neobatrachian-type arrangement. Except for the genus Babina, the monophyly of each genus was well supported. The genus Amnirana occupied the most basal position among the Ranidae. The [Lithobates ＋ Rana] was the closest sister group of Odorrana. The diversity of mitochondrial gene arrangements in ranid species was unexpectedly high, with 47 mitogenomes from 40 ranids being classified into 10 different gene rearrangement types. Some taxa owned their unique gene rearrangement characteristics, which had significant implication for their phylogeny analysis. All rearrangement events discovered in the Ranidae mitogenomes can be explained by the duplication and random loss model.

Bcl-2 GENE REARRANGEMENT DETERMINED BY PCR AS AMEAN TO DETECT MINIMAL RESIDUAL DISEASE INMALIGNANT LYMPHOMAS

Objective: To develop a sensitive method to detect minimal residual disease and to elucidate the significance of bcl-2 gene rearrangement in diagnosis and treatment of malignant lymphoma. Methods: Using polymerase chain reaction (PCR) to detect bcl-2 gene rearrangement and using serial dilution method to define the sensitivity of PCR. Results: In 9 different malignant lymphoma cell lines, Su-DHL-4 and Su-DHL-6 were shown bcl-2(MBR)/JH rearrangement, the sensitivity of PCR was 1:105. In 16 patients with follicular lymphoma, the peripheral blood and bone marrow were PCR positive in 4 cases both at initial diagnosis and after complete remission. Conclusion: Detection of bcl-2 gene rearrangement by PCR provides a sensitive and specific assay of minimal residual disease. It is helpful to improve staging of disease, prognosis and evaluation of the treatment results.

Clonal immunoglobulin heavy chain and T-cell receptor γ gene rearrangements in primary gastric lymphoma

AIM:To study the diagnostic value of immunoglobulin heavy chain(IgH)and T-cell receptorγ (TCR-γ)gene monoclonal rearrangements in primary gastric lymphoma(PGL).METHODS:A total of 48 patients with suspected PGL at our hospital were prospectively enrolled in this study from January 2009 to December 2011.The patients were divided into three groups(a PGL group,a gastric linitis plastica group,and a benign gastric ulcer group)based on the pathological results(gastric mucosal specimens obtained by endoscopy or surgery)and follow-up.Endoscopic ultrasonography(EUS)and EUSguided biopsy were performed in all the patients.The tissue specimens were used for histopathological examination and for IgH and TCR-γ gene rearrangement polymerase chain reaction analyses.RESULTS:EUS and EUS-guided biopsy were successfully performed in all 48 patients.In the PGL group(n=21),monoclonal IgH gene rearrangements were detected in 14(66.7%)patients.A positive result for each set of primers was found in 12(57.1%),8(38.1%),and 4(19.0%)cases using FR1/JH,FR2/JH,and FR3/JH primers,respectively.Overall,12(75%)patients with mucosal-associated lymphoid tissue lymphoma(n=16)and 2(40%)patients with diffuse large B-cell lymphoma(n=5)were positive for monoclonal IgH gene rearrangements.No patients in the gastric linitis plastica group(n=17)and only one(10%)patient in the benign gastric ulcer group(n=10)were positive for a monoclonal IgH gene rearrangement.No TCRgene monoclonal rearrangements were detected.The sensitivity of monoclonal IgH gene rearrangements was 66.7%for a PGL diagnosis,and the specificity was96.4%.In the PGL group,8(100%)patients with stage IIE PGL(n=8)and 6(46.1%)patients with stage IE PGL(n=13)were positive for monoclonal IgH gene rearrangements.CONCLUSION:IgH gene rearrangements may be associated with PGL staging and may be useful for the diagnosis of PGL and for differentiating between PGL and gastric linitis plastica.

Gene Rearrangement Analysis of Orbital Lymphoid Infiltrating Disorders

Purpose:To determine whether the use of polymerase chain reaction for B-cell gene rearrangement in patients with orbital lymphoid infiltrate disorders could be useful in the diagnosis of lymphoma,especially,in differentiating benign lesion from malignant one.Methods:In addition to clinical,pathological,and immunohistochemical evaluations,48 cases of orbital lymphoid infiltrate disorders were examined for immunoglobulin heavy(IgH)gene rearrangement by means of PCRto amplify the FR3region with formalin-fixed and paraffin-embedded tissues.Results:Gene rearrangement in the third frame-work of the IgH region was detected in specimens obtained from15cases of malignant lymphoma,4of reactive lymphoid hyperplasia and3of orbital pseudotumor.All of these patients showed a discrete band(100bp)which reflected monoclonal proliferation of B lymphocytes.5cases of malignant lymphoma,6ofreactive lymphoid hyperplasia and 15of orbital pseudotumor did not show a discrete band on PCR.Conclusions:The FR3 region gene rearrangement of Ig heavy in patients with orbital lymphoid infiltrate disorders may be an additional diagnostic tool in differentiating benign from malignant lymphoid diseases and in offering a useful adjunct for diagnosis in difficult or unclear cases.It is a reliable and practical method of gene diagnosis in orbital lymphoid infiltrate disorders and helps to identify the molecular mechanism of malignant lymhoma.Eye Science2000;16:15-21.

Detection of IgH and T-cell receptor gene rearrangement in leukemia by PCR amplification and its clinical application

PCR amplification was used to detect immunoglobulin heavy chain (IgH), T-cell receptor (TCR)Vγ1-Jγ, Vδ2-Dδ 3 rearranged genes in 45 cases of acute lymphoblastic leukemia (ALL) and IgH gene rearrangement in 41 cases acute nonlymphoblastic leukemia (ANLL). The positive percentage of the IgH, TCR Vγ1-Jγ and Vδ 2-Dδ3 gene rearrangement was found to be 66. 7%, 62.2%, and 35. 6%, respectively in 45 ALL patients. Multiple rearranged IgH gene bands were found in 8 (26. 7% ) out of 30 ALL patients with IgH gene rearrangement. IgH gene rearrangemens were found in 7 (17. 1% ) out of 41 ANLL patients. ALL patients with positive IgH rearranged gene were with B cell and those with positive TCR Vγ1-Jγ gene rearrangements and with negative IgH rearranged gene were with T-ALL,those with positive both IgH and TCR Vδ2-Dδ3 rearranged genes mostly were with preB-ALL. The complete remission (CR) rate was low in ALL patients with multiple rearranged heavy chains and ANLL patients with IgH gene rearrangement, who were more likely to have a clinical relapse, which may be due to clonal evolution. In complete remission (CR) patients, the cytologic relapse fell behind postive PCR results for an average periods of 7. 2 weeks (range 2 to 23 weeks). Using PCR to detect rearranged genes could be helpful in determining the efficacy of chemotherapy, predicting clinical relapse, assisting gene typing and predicting prognosis.

Mitochondrial gene rearrangement within genus Gasteruption(Hymenoptera: Evanioidea: Gasteruptiidae)

The complete mitochondrial genome of the Gasteruption parvicollarium Enderlein （GenBank accession number： KR270643） was sequenced in the study. Totally 17 009 bp sequence was determined with an A＋T content of 83.81%, including full set of typical animal mitochondrial genes. Two protein-coding and 10 tRNA genes as well as the A＋T-rich region were rearranged compared with the putative ancestral arrangement of insects. Most of the rearranged genes were located in the ancestral region of trnl-trnQ-trnM-nad2-trn W-trnC-trn Y- coxl-trnL2. The other rearranged genes are trnN and trnS1 located in the tRNA cluster trnA- trnR-trnN-trnSl-trnE-trnF and trnS2 located between cob and nadl. Remote inversion is dominant rearrangement event in G. parvicollarium mitochondrial genome, involving two protein-coding and 8 tRNA genes. Compared with the other mitochondrial genome reported in the same genus of Gasteruption, the inverted trnN was translocated to the tRNA cluster between cox1 and nad2 in G. parvicollarium. This is the first report of mitochondrial gene rearrangement occurred within genus of Hymenoptera. Our study points to a recently occurred gene rearrangement event in the Gasteruption species.

THE RELATIONSHIP BETWEEN NON-HODGKIN'S LYMPHOMA AND THE GENE REARRANGEMENT

Objective: To investigate the pattern of clonal rearrangement of immunoglobulin heavy chain gene (IGH) and T cell receptor γ gene (TCRγ) of Non Hodgkin's lymphoma (NHL) Methods: Bone marrow smears of 211 patients of NHL were detected by PCR, the rearranged IGH and TCRγ gene was amplified using oligonucleotide primers Results: The clonal rearrangement of IGH gene was detectable in 51 2% (108/211); the clonal rearrangement of TCRγ gene was detectable in 21 3% (45/211); both IGH and TCRγ was detectable in 5 7% (12/211); no clonal rearrangement in 21 8% (46/211) And compared clonal gene rearrangement with pathological type and primary site of tumor Ten patients of NHL were investigated serially 5/10 patients still had clonal gene rearrangement at clinical complete remission Conclusion: It demonstrated that this assay may be useful in monitoring the minimal residual disease (MRD) and in evaluating effectiveness of therapy

T-CELL RECEPTOR GENE REARRANGEMENT ANALYSIS IN THE PRIMARY CUTANEOUS T-CELL LYMPHOMA

Object: The present paper is to evaluate the significance of T cell receptor (TCR) gene rearrange ments in primary cutaneous T cell lymphomas (PCTCL) as detected by analysis of Southern Blot (SBA) and polymerase chain reaction (PCR). Patients and Methods: Skin specimens and peripheral blood samples were taken from 44 patients with PCTCL, including 30 patients with mycosis fungoides (MF), 2 patients with Sezary's syndrome (SS), and 12 patients with PCTCL other than MF and SS (PNCTCL). 11 patients with a presumptive diagnosis of MF, 23 patients with lymphoproliferative dermatoses including lymphomatoid papulosis (LyP) and 8 patients with benign cutaneous lymphoid infiltrates were simultaneously studied by the amplification of junctional V (variable) J (joining) sequences of the rearranged TCRγ genes by PCR(TCRγPCR) and the analysis of TCRb chain genes by SBA(TCRβSBA) for detection of clonal gene rearrangements (GR). One lymph node specimen of a case with MF IIA was also detected by TCRγ PCR and TCRβSBA. Results: In MF, GR were detected by TCRγPCR and TCRβSBAb in 83.3 85.7% and 66.7% 71.4% of skin specimens of cases IIA IIB and in 57.1% 70.0% and 14.3% 10.0% of those of cases IA IB, respectively. GR were seen in 66.7% 71.4% and 33.3% 43.0.% of blood samples of cases IIA IIB, and 42.9% 40.0% and 0 10.0% of those of cases IA IB, respectively. GR was confirmed by TCRγ PCR and TCRβSBA in one lymph node showing dermato pathic lymphadenopathy of a case with MF IIA. In 11 patients of clinically suspected MF, GR were present in skin specimens of 5 cases (45.4%) and in blood samples of 3 cases ( 27.3% ) by TCRγ PCR. In PNCTCL, GR were found in 9 skin specimens (90.0%) from 10 patients detected by TCRγ PCR and in 6 skin specimens (75.0%) from 8 patients detected by TCRβSBA. GR were also seen in 6 blood samples (72.8%) from 11 patients detected by TCRγ PCR, and in 7 blood samples (70.0%) from 10 patients by TCRβSBA. In SS and LyP, GR were detected by TCRγ PCR and TCRβSBA in each of the two skin specimens of two cases with LyP and in each of the two blood samples of two cases with SS. GR were seen in one skin specimen of one case with SS and one blood sample of one case with LyP detected by TCRγPCR. Conclusions: This study demonstrated that TCRγ PCR is a rapid, more sensitive tool than TCRβSBA, can be used in the analysis of T cell clonality in skin, lymph node and blood samples of patients with PCTCL and indicated that this method forms a useful supplement to other methods for diagnosis of early and suspected MF, confirmation of PNCTCL and determination of extracutaneous involvement of lymph node and blood.

γANDδCHAIN GENE REARRANGEMENT OF T CELL RECEPTOR IN ACUTE LYMPHOBLASTIC LEUKEMIA

The immunophenotype, rearrangements of T cell receptor(TCR) γ andδchain genes as well as the immunoglobulinheavy chain (IgH)gene were studied in 37 cases ofmorphologically defined acute lymphoblastic leukemia (ALL).According to the expression of differentiation antigens, 8 caseswere classified as T-ALL, 26 B lineage ALL, 2 acute un-differentiated leukemia (AUL) and myeloid phenotype. An or-der of TCR gene rearrangements was observed in T-ALL,with the rearrangement of δgene preceding that of γgene.Both genes were also found frequently rearranged and / or de-leted in high proportions of the ALL of B cell lineage. Howev-er, the patterns of gene rearrangements were somewhat differ-ent between the T and B lineage ALLs. In contrast, the lgHgene rearrangements were observed only in the B lineage ALL.The immunogenotype analysis of ALL proved to be a usefulmarker of the clonality and provided us with important informa-tion on early human lymphoid differentiation. We concludethat the determination of T

Detection of Immunoglobulin Heavy China and T Cell Receptorγ Gene Rearrangement in Lymph Node Aspirates with PCR:Diagnostic Significance for Lymphoproliferative Disorders

Lymph node aspirates of 17 cases with enlarged superficial or isceral lymph nodes were detected for immunoglobulin heavy chain gene rearrangement (IgHRA) and T cell rcceptor γ gene rearrangement (TCRγRA) bypolymerase chain reaction (PCR). Combining with clinical data, pathologic diagnosis and immunophenotapy, we analyse the results as follows: 5 cases with nonlymphoid cancers and 3 cases with reactive lymphadenopathy do not present two kinds of clone gene rearrangements.5 out of 7 cases with NHL show clone gene rearrangements (IgH 3 cases, TCRY 2cases),two kinds of monoclonal band(100-120bp for IgHRA and 170-230bp for TCRγRA) were observed after electrophoresis of amplified DNA products. One case whose clinical sitcaion accorded with features of lymphoma was diagnosed as granulomatous lymphadenitis by pathologist, after gene rearaangement clone TCRγRA was detected,a correct diaguosis as NHL was made then. The significance of detecting the two kinds of gene rearrangement for clinical application and the limitations in diagnosis of lymphoproliferative disorders was discussed.

Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants

Targeted therapy is crucial for advanced colorectal cancer(CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2(ERBB2), B-Raf proto-oncogene, serine/threonine kinase(BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase(ALK/ROS1), neurotrophic receptor tyrosine kinases(NTRKs), ret proto-oncogene(RET), fibroblast growth factor receptor 2(FGFR2), and epidermal growth factor receptor(EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China.Methods This study included individuals aged 28 days–85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA.Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0–1 year,and RVA is the key pathogen circulating in patients 6–10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains.Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

REARRANGEMENT AND EXPRESSION OF T CELL RECEPTOR β GENE IN HUMAN HEMOPOIETIC CELL LINES AND PRIMARY CELLS FROM ACUTE LYMPHOCYTIC LEUKEMIAS

Using Southern blot, Northern blot and Quick blot methods, we examined the rearrangement and expression of TCR βgene in four early differentiation stage cell lines from human hemopoietic system, namely HL-60, Jurkat, Daudi and Raji cells as well as lymphocytes from 17 acute lymphocytic leukemia （ALL） patients. The results showed. Ⅰ) Rearrangement of TCR βgene was seen in Jurkat cells. A germline pattern was observed in HL-60, Daudi and Raji cells. 2) Eight of 9 patients with T-ALL had cells with rearranged TCR βgene. But two of 3 patients with B-ALL and three of 5 patients with nonT, nonB-ALL also had cells with rearranged TCR βgene. 3) A 1.3 kb full-length transcript and a 1.0 kb truncated transcript were detected in Jurkat cells by probing with 32P-TCR βcDNA. But some leukemic B cells also expressed an incompleted transcript. 4) TCR βmRNA was detected in six of 8 patients with T-ALL, four of 5 patients with nonT, nonB-ALL and one of 3 patients with B-ALL. But the level of expression was quite differ ent. The dual-rearrangement and the abnormal expression may give us a new clue for researching leukemogenesis.

Comparison of Biolistic and Agrobacterium-mediated Transformation Methods on Transgene Copy Number and Rearrangement Frequency in Rice

Transferring foreign DNA into plant cells by biolistic and Agrobacterium _mediated methods may result in random integration of different copy numbers of the transgene, and different proportions of intact vs. rearranged copies of the transgene. This may, in turn, affect transgene expression levels. To test the above hypothesis, we first introduced the same plasmid, pAc1PG_CAM, into rice (Oryza sativa L.) calli separately by the biolistic method and by the Agrobacterium _mediated method. To show whether different plasmids may affect the results, we also introduced pTOK233 by the Agrobacterium _mediated method and pJPM44 by the biolistic method. Transgene expression of R0 plants was monitored by histochemical analysis of GUS activity. Transgene copy number was determined by Southern blot analysis after digesting genomic DNA with an enzyme that has a unique cutting site within the input plasmid. The total genomic DNA was also digested by a two_cut enzyme (the cuts are located at two sides of a given transgene expression cassette), followed by Southern blotting analysis, for determining the number of intact transgene expression cassettes. Our data showed that Agrobacterium _mediated transformation resulted in lower transgene copy number (average between 2.1 and 2.3) in transgenic rice plants, compared with those plants obtained by the biolistic method (average between 4.2 and 5.6). The frequency of DNA rearrangement in expression cassettes is lower in transgenic rice plants obtained by the Agrobacterium _ mediated method than those obtained by the biolistic method. The average rearrangement frequency is 0.07 to 0.106 for the Agrobacterium _mediated method, and 0.57 to 0.66 for the biolistic method. Our results suggest that it is better to compare the number of intact expression cassettes instead of the total copy number of the transgene in demonstrating their influence on the level of transgene expression. This is the first report on the frequency of expression cassette rearrangement in transgenic plants transformed with the same plasmid by two different transformation methods.

Diagnostic significance of TCR gene clonal rearrangement analysis in early mycosis fungoides

Mycosis fungoides(MF),the most common type of cutaneous T-cell lymphoma,has various unspecific clinical and histological characteristics.Its early diagnosis is challenging.The application of T-cell receptor(TCR) gene clonal rearrangement to the diagnosis of MF has been widely studied.In this study,we used polymerase chain reaction(PCR) to investigate the diagnostic significance of detecting TCR-γ and-β gene clonal rearrangement in the early diagnosis of mycosis fungoides.PCR for TCR-γ and TCR-β gene rearrangement was performed on 19 patients with suspected early MF,6 with typical MF,and 6 with chronic dermatitis.Of the 19 patients with suspected early MF,13 had TCR-γ gene clonal rearrangement,whereas none had TCR-β gene clonal rearrangement.All patients with typical MF had TCR gene clonal rearrangement,in which 4 showed TCR-γ clonal rearrangement,1 showed TCR-β gene clonal rearrangements,and 1 showed both.No patients with chronic dermatitis had TCR gene clonal rearrangement.These results indicate that TCR gene clonal rearrangement analysis is a useful tool in diagnosing early MF.TCR-γ gene is recommended to the routine analysis,whereas TCR-β gene has potential in combination toward intractable cases.

Menin-MLL蛋白相互作用及相关抑制剂在MLL基因重排白血病中应用的研究进展

混合谱系白血病(mixed lineage leukemia,MLL)基因重排(MLL-rearranged,MLL-r)引起的急性白血病亚型侵袭性高且预后不良,缺少特异性治疗手段。MLL蛋白具有组蛋白甲基转移酶活性,在胚胎发育和正常造血中必不可少,可通过功能结构域与多种蛋白质相互作用,形成大分子复合体,并通过表观修饰调节下游靶基因的表达。MLL-r转录形成MLL融合蛋白(MLL fusion protein,MLL-FP),其中MLL蛋白的C端被融合伙伴蛋白所取代。现已发现超过100种融合伙伴蛋白。分子机制研究发现,Menin蛋白是MLL-FP致白血病必不可少的辅助因子,通过与MLL-N端特定区域相互作用形成关键致病复合体,导致特定靶基因的异常表达。这为Menin-MLL相互作用抑制剂的开发提供了理论依据。截至目前,多种小分子化合物被发现能抑制Menin-MLL相互作用,包括噻吩嘧啶类、哌啶类、嘧啶类和大环拟肽类。至少7种以此为原型开发的药物进入临床试验,部分已在安全性、耐受性和疗效方面取得乐观的初步数据。该文从MLL蛋白的结构功能、MLL-r导致白血病的机制出发,对Menin-MLL蛋白相互作用抑制剂在MLL-r白血病中应用的研究进展进行综述。

CD19/CD22 CAR-T细胞治疗MLL基因重排阳性难治/复发儿童急性B系淋巴细胞白血病临床分析

目的 分析双靶点CD19/CD22嵌合抗原受体T(CAR-T)细胞治疗混合谱系白血病基因重排(MLL-r)阳性难治/复发急性B系淋巴细胞白血病(R/R B-ALL)患儿的有效性及安全性。方法 回顾性分析2019年10月至2021年11月接受双靶点CD19/CD22 CAR-T治疗的MLL-r阳性R/R B-ALL患儿的临床资料。结果 共纳入37例MLL-r阳性R/R B-ALL患儿,男24例、女13例,诊断时中位年龄1.2(0.5~2.6)岁,其中17例(45.9%)为婴儿白血病。CAR-T细胞输注后中位时间9(7~13)天,37例患儿的完全缓解率达100%。中位随访时间28.2(11.3~30.9)个月,3年总体生存(OS)率为67.6%(95%CI:52.5%~82.7%),3年无事件生存率为59.5%(95%CI:43.6%~75.4%)。75.7%(28/37)的患者在CAR-T细胞治疗后接受过异基因造血干细胞移植,移植距离CAR-T细胞输注的中位时间为83(61~92)天。接受巩固性移植与未接受患儿的2年OS分别为75.0%(95%CI:58.9~91.1%)与44.4%(95%CI:11.9%~76.9%),差异无统计学意义(P=0.068)。35.1%(13/37)的患儿复发,中位复发时间为156(86~202)天,其中4例为CD19、CD22双阳性复发,2例CD19、CD22双阴性复发,4例单纯CD19阴性复发,1例淋系向髓系转化,另2例不明确。97.3%(36/37)患儿发生了细胞因子释放综合征,11例(29.7%)达到了3~4级,5例(13.5%)患儿出现了免疫效应细胞相关神经毒性综合征;无CAR-T细胞治疗合并症导致的死亡。结论 CD19/CD22 CAR-T细胞治疗可有效诱导MLL-r阳性儿童R/R B-ALL获得快速缓解,且不良反应可耐受。

IMMUNOGLOBULIN GENE REARRANGEMENT IN LYMPHOID TUMORS

Ⅰ. INTRODUCTIONThere are immunoglobulins (Ig) and T cell receptors (TCR) on the surfaces of lymphocytes, which are able to transfer external messages. All the Ig and TCR genes originated in immunoglobulin gene superfamily, and some functive genes have been translated

STUDY ON THE RFLPs AND AMPLICATION AND REARRANGEMENT OF THE TRANSFORMING GENES IN PRIMARY HEPATIC CARCINOMA, GASTRIC CARCINOMA AND BRAIN TUMOR WITH SIX HUMAN ONCOGENE PROBES

By using c-Ha-ras-1, N-ras Wigler (left sequence) and P52C.(right sequence), c-sis, v-erbB, c-myc and v-fos oncogenes as probes, restriction fragment length polymorphisms (RFLPs) of tumor tissue DNAs of 95 patients with gastric carcinoma, primary hepatic carcinoma and brain tumor, and those of 90 normal individuals were studied with the techniques of Southern blot and dot blot. Gene amplification and recombination were also examined in some tumors simultaneously. Some alleles of oncogene are reported in Chinese population for the first time. Moreover, the characteristic frequency of some "rare" alleles and genotypes occurred in some tumor samples is significantly higher than that occured in normal individuals. Pedigree analysis for 2 patients showed that some "rare" alleles are also abandant. Besides, gene amplification and recombination were found in some tumors.

MLL基因重排在成人急性白血病中的检测和临床特征研究

混合系白血病(MLL)发生基因重排在成人急性白血病中相关研究较少。本研究通过3种技术组合检测MLL基因重排,探究其在成人急性白血病中的发生率、伙伴基因类型、伴MLL基因重排的急性白血病临床特征和预后并评估该组合检测的临床应用价值。对183例成人急性白血病患者采用常规细胞遗传学、分离信号FISH和多重巢式PCR 3种技术组合检测MLL基因重排。结果显示,成人急性白血病中MLL基因重排发生率低(8.2%);重排类型在急性淋巴细胞白血病(ALL)中MLL-AF4最常见,急性髓系白血病(AML)中MLL-AF6和MLL-AF9最常见;MLL基因重排患者髓外浸润占40%,诱导治疗30 d内完全缓解率33.3%,3个月复发率和6个月生存率各为50.0%和50.0%。结论:本研究中常规细胞遗传学技术对MLL基因重排的漏检率高达60%,因此常规细胞遗传学,分离信号FISH和多重巢式PCR结合检测MLL基因重排具有重要的预后意义和指导临床治疗价值。