Management of Acute Myeloblastic Leukaemia (AML) Treated with Intensive Chemotherapy: Experience in a Single Centre

Introduction: Acute myeloblastic leukaemia (AML) is a haematological malignancy with a poor prognosis, despite significant therapeutic progress. This study presents the results of AML management in Mali according to GFAOP recommendations. Methodology: This was a retrospective, cross-sectional study. It included patients aged 0 - 15 years treated in the paediatric oncology unit for AML and followed up between January 2016 and December 2020. Results: During the study period, 85 cases of acute leukaemia were diagnosed in the paediatric oncology unit (including 51 cases of ALL), of which 34 cases of AML were included in this study. The majority were boys (59%). The mean age was 8 years, with extremes of 18 months and 15 years. The mean time to diagnosis was 68 days. In 79% of cases, patients were referred by 1st or 2nd level hospitals. Anaemia was observed in 91% of cases, an infectious syndrome in 68%, haemorrhage in 56% and a tumour syndrome in 85%. The haemogram showed hyperleukocytosis in 15% of cases, thrombocytosis in 22% and severe anaemia in 73%. Death occurred in 85% of cases, most often in the context of sepsis or haemorrhage. Conclusion: AML is probably underestimated in Mali and diagnosis delayed, which may be explained by patient-related factors (lack of knowledge, financial constraints) and a cumbersome referral system. These results suggest the need to implement an appropriate diagnostic and therapeutic strategy, with strong involvement of the political authorities.

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a non-Hodgkin lymphoma that originates in the central nervous system(CNS)and is exclusively limited to the CNS.Although most PCNSLs are diffuse large B-cell lymphomas,primary CNS T-cell lymphomas(PCNSTLs)are rare.PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging(MRI).To the best of our knowledge,non-enhancing PCNSTL has not been reported previously.CASE SUMMARY A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks.Initial MRI showed asymmetric T2-hyperintense lesions within the brain.No enhancement was observed on the contrast-enhanced T1 image.The initial diagnosis was neuro-Behçet’s disease.Despite high-dose steroid therapy,no alterations in the lesions were identified on initial MRI.The patient’s symptoms deteriorated further.An MRI performed one month after the initial scan revealed an increased lesion extent.Subsequently,brain biopsy confirmed the diagnosis of PCNSTL.The patient underwent definitive combined chemoradiotherapy.However,the patient developed bacteremia and died of septic shock approximately three months after diagnosis.CONCLUSION The absence of enhancement in the lesion did not rule out PCNSTL.A biopsy approach is advisable for pathological confirmation.

Mutations in Ras homolog family member A in patients with peripheral T-cell lymphoma and implications for personalized medicine

Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type,thereby leading to different functional and biological properties,which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors.However,the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated.Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways.The promising potential of targeting RHOA as a therapeutic modality is also outlined.This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.

Plasmacytosis mimicking multiple myeloma in angioimmunoblastic T-cell lymphoma:A case report and review of literature

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL)is a common subtype of peripheral T-cell lymphoma.Approximately half of patients with AITL may concurrently present with hypergammaglobulinemia.Increased numbers of plasma cells in the bone marrow are commonly observed at diagnosis.These tumors mimic plasma cell myelomas,hindering a conundrum of clinical diagnoses and potentially delaying appropriate treatment.CASE SUMMARY A 78-year-old woman experienced poor appetite,weight loss of 5 kg,fatigue 2 months before presentation,and shortness of breath 2 d before presentation,but no fever or night sweats.Physical examination revealed splenomegaly and many palpable masses over the bilateral axillary regions,approximately>2 cm in size,with rubbery consistency and no tenderness.Blood tests revealed anemia and thrombocytopenia,lactate dehydrogenase level of 153 U/L,total protein level of 10.9 g/dL,albumin to globulin ratio of 0.2,and immunoglobulin G level more than the upper limit of 3000 mg/dL.The free kappa and lambda light chain concentrations were 451 and 614 mg/L,respectively.A pathological examination confirmed the diagnosis of AITL.The initial treatment was the cyclophosphamide,epirubicin,vincristine,and prednisolone regimen.Following this treatment,pleural effusion was controlled,and the patient was discharged in a stable condition and followed up in our outpatient department.CONCLUSION This report highlights the importance of differentiating reactive plasmacytosis from plasma cell myeloma in patients with hypergammaglobulinemia.A precise diagnosis of AITL requires a comprehensive evaluation,involving clinical,immunophenotypic,and histological findings conducted by a multidisciplinary team to ensure appropriate treatment.

Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report

BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.

New perspective on the treatment of rheumatic arthritis based on“strengthening body resistance(FúZhèng)”in the theory of co-inhibitory receptor-regulated T-cell immunity

Co-inhibitory receptors serve as crucial regulators of T-cell function,playing a pivotal role in modulating the delicate balance between immune tolerance and autoimmunity.Initially identified in autoimmune disease models,co-inhibitory receptors,including CTLA-4,PD-1,TIM-3,and TIGIT,were found to be integral to immune regulation.Their blockade or absence in these models resulted in the induction or exacerbation of autoimmune diseases.Additionally,scholars have observed that co-inhibitory receptors on lymphocytes hold the potential to influence the prognosis in the context of chronic inflammation.Consequently,the blocking of co-suppressor receptors has emerged as a novel therapeutic approach for inhibiting refractory inflammatory diseases,particularly rheumatoid arthritis.From the standpoint of traditional Chinese medicine(TCM),the treatment of rheumatoid arthritis based on the“strengthening body resistance(FúZhèng)”theory can be construed as the regulation of co-suppressor receptors to modulate the body’s immune function in combating chronic inflammation.This article provides a succinct overview of the role of co-suppressor receptors in anti-inflammatory processes and explores the research prospects of co-suppressor receptor intervention in the treatment of rheumatoid arthritis.The exploration integrates the“strengthening body resistance(FúZhèng)”theory with relevant Chinese medicine formulations.

Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy(CAR–T)cell immunotherapy

Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementing this novel targeted cell therapy are increasingly significant.Particularly in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy.These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach.In this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its efficacy.Furthermore,we aim to identify existing solution strategies and explore their current research status.Through this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications.

Investigation of the Clinical Diagnostic Significance of the T-Cell Test for Tuberculosis combined with Erythrocyte Sedimentation Test in Pulmonary Tuberculosis

Objective:To investigate the clinical diagnostic significance of peripheral blood T-cell test(T-spot test)for tuberculosis(TB)infection combined with erythrocyte sedimentation rate(ESR)in pulmonary TB.Methods:41 patients with a clinical diagnosis of TB during hospitalization from January 2020 to April 2023 in our hospital were selected as the experimental group,and 45 patients without TB(bronchopneumonia patients)were selected as the control group.The diagnostic specificity,sensitivity,and accuracy of the T-spot TB test,ESR test,and the combined test of the two were calculated respectively.Results:The sensitivity,specificity,and accuracy of the T-spot TB test combined with ESR for the diagnosis of TB in the experimental group were significantly higher than the individual results of the T-spot TB test and ESR test alone(P<0.05).Conclusion:The T-spot TB test combined with the ESR test for TB diagnosis has greater clinical value than carrying out the tests individually.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Transcriptome sequencing analysis of ursolic acid-mediated proliferation suppression on cutaneous T-cell lymphoma cells

Background:Ursolic acid is a triterpenoid compound found in natural plants that exhibits antiproliferative effects in various cancer cells.Our study is the first to demonstrate the strong inhibitory effects of ursolic acid on the proliferation of cutaneous T-cell lymphoma(CTCL)cells.We aimed to further investigate the underlying mechanism of the proliferation inhibition induced by ursolic acid in CTCL cells using transcriptome sequencing.Methods:Cell counting kit-8 assays were used to observe the effects of six traditional medicine monomers on the proliferation of CTCL cells.Transcriptome sequencing was used to identify differentially expressed genes after ursolic acid treatment.Bioinformatics analysis was performed to determine the potential mechanism.Real-time quantitative PCR and western blotting analyses were performed to confirm the sequencing results and verify the possible mechanisms of ursolic acid-mediated proliferation inhibition in CTCL cells.Results:Ursolic acid exhibited the strongest inhibitory effect on the proliferation of CTCL cells among the six traditional medicine monomers.Transcriptome sequencing analysis showed that 2,466 genes were significantly altered.Combined with Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and protein-protein interaction network analysis,the interaction of various pathways and signaling molecules,such as tumor necrosis factor-α,NLR family pyrin domain containing 1,c-Jun N-terminal kinase,and melanoma differentiation-associated gene 5,accounted for the anti-tumor effects of ursolic acid in CTCL cells.Conclusion:Ursolic acid significantly inhibited the proliferation of CTCL cells,and our study laid a theoretical foundation for the future treatment of CTCL using ursolic acid.

Angioimmunoblastic T-cell lymphoma induced hemophagocytic lymphohistiocytosis and disseminated intravascular coagulopathy: A case report

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL) is a subtype of peripheral T-cell lymphoma, with heterogenous clinical manifestations and poor prognosis. Here,we report a case of AITL induced hemophagocytic lymphohistiocytosis(HLH)and disseminated intravascular coagulopathy(DIC).CASE SUMMARY An 83-year-old man presented with fever and purpura of both lower limbs for one month. Groin lymph node puncture and flow cytometry indicated a diagnosis of AITL. Bone marrow examination and other laboratory related indexes indicated DIC and HLH. The patient rapidly succumbed to gastrointestinal bleeding and septic shock.CONCLUSION This is the first reported case of AITL induced HLH and DIC. AITL is more aggressive in older adults. In addition to male gender, mediastinal lymphadenopathy, anaemia, and sustained high level of neutrophil-to-lymphocyte ratio may indicate a greater risk of death. Early diagnosis, early detection of severe complications, and prompt and effective treatment are vital.

Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion:A case report

BACKGROUND Intestinal natural killer/T-cell lymphoma(NKTCL)is a rare and aggressive non-Hodgkin’s lymphoma,and its occurrence is closely related to Epstein-Barr virus infection.In addition,the clinical symptoms of NKTCL are not obvious,and the specific pathogenesis is still uncertain.While NKTCL may occur in any segment of the intestinal tract,its distinct location in the periampullary region,which leads clinicians to consider mimics of a pancreatic head mass,should also be addressed.Therefore,there remain huge challenges in the diagnosis and treatment of intestinal NKTCL.CASE SUMMARY In this case,we introduce a male who presented to the clinic with edema of both lower limbs,accompanied by diarrhea,and abdominal pain.Endoscopic ultrasound(EUS)showed well-defined homogeneous hypoechoic lesions with abundant blood flow signals and compression signs in the head of the pancreas.Under the guidance of EUS-fine needle biopsy(FNB)with 19 gauge or 22 gauge needles,combined with multicolor flow cytometry immunophenotyping(MFCI)helped us diagnose NKTCL.During treatments,the patient was prescribed the steroid(dexamethasone),methotrexate,ifosfamide,L-asparaginase,and etoposide chemotherapy regimen.Unfortunately,he died of leukopenia and severe septic shock in a local hospital.CONCLUSION Clinicians should enhance their understanding of NKTCL.Some key factors,including EUS characteristics,the right choice of FNB needle,and combination with MFCI,are crucial for improving the diagnostic rate and reducing the misdiagnosis rate.

The Role of Mitochondrial VDAC2 in the Survival and Proliferation of T-Cell Acute Lymphoblastic Leukemia Cells

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with aberrant T-cell developmental arrest. Individuals with relapsed T-ALL have limited therapeutic alternatives and poor prognosis. The mitochondrial function is critical for the T-cell viability. The voltage-dependent anion channel 2 (VDAC2) in the mitochondrial outer membrane, interacts with pro-apoptotic BCL-2 proteins and mediates the apoptosis of several cancer cell lines. Objective: The aim of the current study is to explore the role of VDAC2 in T-ALL cell survival and proliferation. Methods: Publicly available datasets of RNA-seq results were analyzed for expression of VDAC isoforms and T-ALL cell lines were treated with a VDAC2 small molecular inhibitor erastin. A VDAC2 RNA interference (siRNA) was delivered to T-ALL cell lines using a retroviral vector. Functional assays were performed to investigate the VDAC2 siRNA impacts on cell proliferation, apoptosis and survival of T-ALL cells. Results: Our analysis found a high expression of VDAC2 mRNA in various T-ALL cell lines. Public datasets of T-ALL RNA-seq also showed that VDAC2 is highly expressed in T-ALL (116.2 ± 36.7), compared to control groups. Only two T-ALL cell lines showed sensitivity to erastin (20 μM) after 48 hours of incubation, including Jurkat (IC50 = 3.943 μM) and Molt4 (IC50 = 3.286 μM), while another two T-ALL cells (CUTLL1 and RPMI 8402) had unstable IC50. However, five T-ALL cell lines (LOUCY, CCRF-CEM, P12-ICHI, HPB-ALL, and PEER cells) showed resistance to erastin. On the contrary, all T-ALL cell lines genetically inhibited with VDAC2 siRNA led to more than 80% decrease in VDAC2 mRNA levels, and a Conclusion: VDAC2 is highly expressed in T-ALL cells. The inhibition of VDAC2 significantly decreased cell viability, increased apoptosis, reduced cell proliferation and caused cell cycle sub-G1 arrest of T-ALL cells.

Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma:A case report

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.

Miller Fisher Syndrome Induced by Chemotherapy in Known Case of Acute Lymphocytic Leukaemia: A Case Report

Introduction: Guillain-Barre Syndrome (GBS) is an acute-onset autoimmune-mediated neuropathy. Guillain-Barre Syndrome can be divided into three subtypes: acute inflammatory demyelinating poly-radiculo-neuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor sensory axonal neuropathy (AMSAN). About 20% of patients with GBS develop respiratory failure and require mechanical ventilation. We are presenting a variant of GBS (Miller Fisher Syndrome, or MFS), which has been confirmed by nerve conduction studies along with the triad of ophthalmoplegia, ataxia, and areflexia. The objective of this study is to present a rare case of chemotherapy-induced GBS. Important clinic findings: A 25-year-old gentleman with acute lymphocytic leukemia on active chemotherapy treatment presented with lower limb weakness. This weakness started after his fifth chemotherapy session. After the sixth chemotherapy, he developed complete paralysis of the left lower limb. Later, he developed right lower limb paralysis. He was also complaining of eye dryness and incomplete closure of both eyes. While inpatient, he developed upper-limb weakness. His chemotherapy consisted of MESNA, cyclophosphamide, doxorubicin, vincristine, cyorabine, and methotrexate. He had ptosis and ophthalmoplegia in the left abducent and right oculomotor regions. He had bilateral facial nerve palsy. He was hypotonic with power grade 3 in the upper limbs and grade 0 in the lower limbs with areflexia. His sensation was intact in the upper limbs but lost in the lower limbs. His planter reflexes were mute. Diagnoses and Management: Intravenous immunoglobulins were given for 5 days. A nerve conduction study showed severe demyelinating sensorimotor polyradoculoneuropathy with secondary axonal loss. The triad of ataxia, ophthalmoplegia, and areflexia was consistent with MFS. The patient improved over the course of the hospital stay but did not reach full recovery. Conclusion: Although GBS is uncommon, it must be taken into account when making a differential diagnosis for any patient presenting with progressive weakness. Drug history is important in all GBS cases.

敲降CD36抑制白血病细胞培养上清液介导的血小板活化

目的:评估干扰CD36表达白血病细胞培养上清液对血小板活化的影响及其机制。方法:利用L1210小鼠白血病细胞上清液培养血小板4、6、12、24 h,以普通培养基培养血小板作为对照,通过流式细胞术检测血小板活化标志物P-选择素(CD62P)的表达,WB法检测CD36表达,确定上清液活化血小板最佳时间。构建CD36干扰载体转染至活化的血小板中,实验分为对照组、模型组、CD36干扰空载体组(si-CD36 NC)、CD36干扰组(si-CD36)、抑制剂组(i CRT3)、抑制剂+CD36干扰组(iCRT3+si-CD36),CCK-8法检测血小板活力,流式细胞术检测血小板中CD62P表达,WB法检测血小板中PECAM-1、CD36、β-catenin蛋白表达。结果:L1210小鼠白血病细胞上清液活化血小板最佳时间为12 h。与对照组相比,模型组血小板活力、CD62P表达、PECAM-1、CD36、β-catenin蛋白表达均显著上升(均P<0.01)。与模型组相比,si-CD36和iCR73组血小板活力、CD62P表达、PECAM-1、CD36、β-catenin蛋白表达均显著下降(均P<0.01)。与iCRT3组相比,iCRT3+si-CD36组变化更为显著。结论:CD36干扰抑制β-catenin蛋白表达,协同Wnt/β-catenin通路抑制剂,进而抑制小鼠白血病细胞上清液介导的血小板活化。

人类重组激活基因与血液系统恶性疾病相关性研究进展

人类重组激活基因(RAG)是人体免疫系统发育和适应性免疫反应的关键基因,它通过调节基因重组过程,导致T和B细胞的受体多样性。已有报道表明人类RAG在不同血液系统恶性疾病的表达存在差异性如骨髓增生异常综合征、急性淋巴细胞白血病等,且RAG基因异常与血液系统肿瘤的发生、发展及预后有关,探讨人类重组激活基因与血液系统恶性疾病的相关性可能为研究其发病机制、治疗及预后判断提供理论及方向。目前尚未见RAG基因与血液系统恶性疾病关系的综合阐述,该文重点将人类RAG基因与骨髓增生异常综合征、白血病、淋巴瘤的相关性进行综述,以期为血液系统恶性疾病的诊治提供新思路。

禽白血病的病理及分子生物学诊断

【目的】了解新疆某市鸡群E型禽白血病(E-avian leukosis)的感染情况及基因分子特征,为禽白血病的诊断和防控提供参考。【方法】本研究通过病理剖检、病理组织学观察、PCR检测、克隆载体连接等对疑似禽白血病病例进行实验室诊断,并通过DNAStar软件将分离株与参考毒株进行env基因核苷酸序列相似性比对、系统进化树构建和变异位点分析。【结果】发病鸡肝脏、心脏、脾脏、肾脏、肺脏等器官肿大,有大小不一的白色结节状病灶。病理组织学观察病灶为大小一致的成淋巴细胞,呈局灶性、弥漫性分布。禽白血病病毒(Avian leukaemia virus, ALV)基因组PCR扩增结果显示,获得大小为302 bp的目的条带,为ALV阳性;对阳性样品进行分型鉴定,阳性样品出现大小为1 074 bp的ALV-E特异性条带,分别命名为AKS2101和AKS2102。序列分析结果显示,分离株与E亚群毒株序列相似性为91.6%~98.6%。系统进化树显示,所得序列与ALV-E亚群参考株处于同一分支,与A、B、C、D、J、K亚群参考株处于不同进化分支,进一步说明该鸡群存在ALV-E感染。基因变异分析显示,分离株存在24处核苷酸变异和17处氨基酸位点变异,且可变位点位于序列高变区。【结论】新疆某市鸡群存在ALV-E感染,本试验为明确该地禽白血病流行情况提供基础数据。

CEBPA双突变合并GATA2种系突变急性髓系白血病1例

患者确诊为急性髓系白血病伴有CEBPA双突变、GATA2、IKZF1突变,给予2个疗程的IA方案(去甲氧柔红霉素、阿糖胞苷)治疗后复发,又给予4个疗程的阿扎胞苷联合venetodax治疗出现短暂缓解,后因未规律治疗再次复发。本文主要分析CEBPA双突变联合GATA2种系突变在急性髓系白血病中的治疗及预后作用。