The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By takin...The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By taking these factors into account, the study aims to explore how existing cancer registry data can aid in the early detection and effective treatment of ALL in patients. Our hypothesis was that statistically significant correlations exist between race, age at which patients were diagnosed, sex, and phenotype of the ALL patients, and their rate of incidence and survivability data were evaluated using SEER*Stat statistical software from National Cancer Institute. Analysis of the incidence data revealed that a higher prevalence of ALL was among the Caucasian population. The majority of ALL cases (59%) occurred in patients aged between 0 to 19 years at the time of diagnosis, and 56% of the affected individuals were male. The B-cell phenotype was predominantly associated with ALL cases (73%). When analyzing survivability data, it was observed that the 5-year survival rates slightly exceeded the 10-year survival rates for the respective demographics. Survivability rates of African Americans patients were the lowest compared to Caucasian, Asian, Pacific Islanders, Alaskan Native, Native Americans and others. Survivability rates progressively decreased for older patients. Moreover, this study investigated the typical treatment methods applied to ALL patients, mainly comprising chemotherapy, with occasional supplementation of radiation therapy as required. The study demonstrated the considerable efficacy of chemotherapy in enhancing patients’ chances of survival, while those who remained untreated faced a less favorable prognosis from the disease. Although a significant amount of data and information exists, this study can help doctors in the future by diagnosing patients with certain characteristics. It will further assist the health care professionals in screening potential patients and early detection of cases. This could also save the lives of elderly patients who have a higher mortality rate from this disease.展开更多
BACKGROUND The concurrence of acute myeloid leukemia(AML)and chronic lymphocytic leukemia(CLL)is rare.Previous reports of such cases have focused mainly on clinical diagnosis and characteristics,so the mechanism remai...BACKGROUND The concurrence of acute myeloid leukemia(AML)and chronic lymphocytic leukemia(CLL)is rare.Previous reports of such cases have focused mainly on clinical diagnosis and characteristics,so the mechanism remains unclear,and therapy options have been poorly explored.CASE SUMMARY Here,we report two cases of synchronous AML and CLL.Flow cytometry revealed two distinct abnormal cell populations(myeloblasts and lymphoid cells)according to scatter characteristics.CD5-positive B cell lymphoma with myeloid leukemia invasion was observed on lymph node biopsy.Chemotherapy regimens indicated for both AML and CLL were used in our patients,and our patients achieved complete response after chemotherapy.Next-generation sequencing of 88 genes was performed.CONCLUSION We conclude that early mutation and dysregulation at the hematopoietic stem cell stage and the accumulation of multiple rearrangements may cause the concurrence of CLL and AML.The treatment of infection and combination therapy aimed at the CLL component are significant in the management of patients with concurrent CLL and AML.展开更多
BACKGROUND In recent years,the rate of immunosuppressed patients has increased rapidly.Invasive fungal infections usually occur in these patients,especially those who have had hematological malignances and received ch...BACKGROUND In recent years,the rate of immunosuppressed patients has increased rapidly.Invasive fungal infections usually occur in these patients,especially those who have had hematological malignances and received chemotherapy.Fusariosis is a rare pathogenic fungus,it can lead to severely invasive Fusarium infections.Along with the increased rate of immune compromised patients,the incidence of invasive Fusarium infections has also increased from the past few years.Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection.CASE SUMMARY We report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin,eyeball,and knee joint during the course of chemotherapy.We performed skin biopsy,microbial cultivation,and molecular biological identification,and the pathogenic fungus was finally confirmed to be Fusarium solani.The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily,and surgical debridement.Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery.The disseminated Fusarium solani infection eventually resolved,and there was no recurrence at the 3 mo follow-up.CONCLUSION Our case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection.These are important to prevent progression to a more aggressive infection.Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy.Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.展开更多
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,...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 <sup>32</sup>P-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.展开更多
Procaine and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemlc cells. In this study, the combined effects of procaine and hyperthermia on the growth of hematopoietic progenitors (...Procaine and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemlc cells. In this study, the combined effects of procaine and hyperthermia on the growth of hematopoietic progenitors (GM-CFU) and ieukemic progenitors (L-CFU) were examined to determine if this combination resulted in a great selective killing of leukemlc cells than that achieved by procaine or heat alone. When the cells were treated simutaneously with procaine (2 mM) and hyperthermia (42℃) for one hour, the killing of L-CFU was enhanced considerably whereas GM-CFU were not markedly affected. These data Indicate that the combined treatment with procain and hyperthermia might offer an efficient mean to selectively purge residual leukemlc cells in vitro. Procaine with hyperthermia may have a role in clinical autoiogous bone marrow transplantation for acute leukemia.展开更多
Objective: Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy at which short survival may be seen. Our study aims to evaluate the effect of the neutrophil-to-lymphocyte ratio (NLR) on the course o...Objective: Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy at which short survival may be seen. Our study aims to evaluate the effect of the neutrophil-to-lymphocyte ratio (NLR) on the course of the disease, response to therapy, and overall survival (OS). Materials and Methods: A total of 124 patients followed-up with the diagnosis of AML from 2016 to 2019 were retrospectively examined. Results: 69 of the cases (55.6%) were men and 55 (44.3%) were women. The average age at the time of diagnosis was 53.44 ± 30.3 years old. We determined the NLR as median 0.46 (0.16 - 1.1). In AML, 69 patients were responsive to the induction regimen (57.9%) while 46 patients were unresponsive (37.8%). 5 patients died before completing the regimen. D-dimer was found to be higher and fibrinogen was found to be lower in the responsive group. Lower OS was observed in cases of >60 years of age, male gender, non-APL AML, high NLR, and recurrence at diagnosis. Recurrences were detected in 23 patients (18.5%) and the median time to the recurrence was 416 (236 - 639) days. Fibrinogen level and the bone marrow blast ratio at the time of application were determined to be associated with recurrence. The median follow-up time was 856 (143 - 1276) days. Final condition analysis reveals that 74 patients (59.6%) are alive. Conclusion: We determined in our study that the NLR is effective on survival. Medical literature on this subject is scanty and prospective studies with large patient groups are needed.展开更多
Childhood survivors of acute lymphoblastic leukemia (ALL) are increased risk of several chronic complications, such as second cancers, pulmonary, metabolic complications and cardiovascular disease. Obesity and metabol...Childhood survivors of acute lymphoblastic leukemia (ALL) are increased risk of several chronic complications, such as second cancers, pulmonary, metabolic complications and cardiovascular disease. Obesity and metabolic syndrome is one of the most common treatment related complication in children surviving cancer, which concurs with our nations childhood epidemic [1-3] Recent research has identified the role of genetics in the development of obesity and metabolic syndrome in childhood survivors of ALL. Growth hormone deficiency, Leptin regulation, fat mass obesity (FTO) gene and the insulin resistant ENPP1 variants disorders has been associated adverse effects of chemotherapeutic treatment and the cause of clinical manifestations of metabolic syndrome [4-8]. The illumination of the role of genetic variants can shed insights into obesity within high risk population, as well as, a target to prevent disease.展开更多
BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diag...BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.展开更多
AIM To examine the optimal absolute lymphocyte count(ALC) cut-off utilizing receiver operator characteristics(ROC) in addition to graft characteristics associated with early ALC recovery.METHODS Patients who received ...AIM To examine the optimal absolute lymphocyte count(ALC) cut-off utilizing receiver operator characteristics(ROC) in addition to graft characteristics associated with early ALC recovery.METHODS Patients who received T-cell replete peripheral hematopoietic cell transplantation(HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes. RESULTS A total of 72 patients met the inclusion criteria andwere analyzed. Optimal ALC cut-off was established to be on day 14(D14) with ALC > 0.3 × 10~9/L. At 2 years, cumulative incidence of relapse was 16.9% vs 46.9%(P = 0.025) for early and delayed lymphocyte recovery cohorts, respectively. Chronic graft vs host disease was more prevalent in the early lymphocyte recovery(ELR) group at 70% vs 27%, respectively(P = 0.0006). On multivariable analysis for relapse, ELR retained its prognostic significance with HR = 0.27(0.05-0.94, P = 0.038).CONCLUSION ELR is an independent predictor for relapse in patients receiving allogeneic HCT for acute leukemia. ELR was influenced by graft characteristics particularly CD34 count.展开更多
Objective To study the changes of lymphocyte subsets and regulatory T cells in peripheral blood of patients with acute leukemia(AL) and its clinical significance.Methods The different levels of peripheral blood lympho...Objective To study the changes of lymphocyte subsets and regulatory T cells in peripheral blood of patients with acute leukemia(AL) and its clinical significance.Methods The different levels of peripheral blood lymphocyte subsets and regulatory T cells of 60 AL patients and 40 normal controls were detected with flow cytometry.Results Compared with the normal controls,the percentages of CD3+ T cells,CD4+ T cells,CD16+CD56+ NK cells and the ratio of CD4+ /CD8+ obviously decreased in newly diagnosed AL group(P <0.05),while their percentages of CD8+ T cells and CD19+ B cells significantly increased(P <0.01).The percentage of CD4+ T cells and the ratio of CD4+ /CD8+ in acute lymphoblastic leukemia(ALL) group were much lower than those in acute myelogenous leukemia(AML) group(P <0.01).Compared with these in control group,the proportions of CD4+ CD25high Treg cells and CD4+ CD25+ T cells in newly diagnosed AL group were significantly increased(P <0.01).Conclusion Cellular immune function is significantly abnormal in patients with AL.Compared with AML patients,ALL patients had poorer cellular immune function.The increased CD4 + CD25high Treg cells might be one of the important reasons of immunosuppression in AL.Detection of lymphocyte subsets and regulatory T cells is of clinical value on the evaluation of therapeutic effect and prognosis in AL patients.展开更多
BACKGROUND Acute myeloid leukemia is often associated with gene mutation or chromosome abnormality,which is an important factor affecting prognosis.The 5-year survival rate of patients with acute myeloid leukemia with...BACKGROUND Acute myeloid leukemia is often associated with gene mutation or chromosome abnormality,which is an important factor affecting prognosis.The 5-year survival rate of patients with acute myeloid leukemia without hematopoietic stem cell transplantation is low.For patients who only received chemotherapy and whose first remission lasted>5 years,there are few reports of gene spectrum changes between relapse and initial diagnosis.CASE SUMMARY We report a 41-year-old woman who presented to our hospital with complaints of dizziness,poor appetite and wasting.She was diagnosed with acute myelomonocytic leukemia(M4b)with NPM1 mutation and only received chemotherapy.Her first remission lasted>5 years.New genetic variants were detected upon relapse that may have been related to relapse and chemotherapy resistance.CONCLUSION Mutations in WT1(R394fs/A387fs)/PTPN11 T73I/ETV6 S350P and JAK2 W659R may be related to relapse and chemotherapy resistance in acute myeloid leukemia.展开更多
Background:For patients with B cell acute lymphocytic leukemia(B-ALL)who underwent allogeneic stem cell transplantation(allo-SCT),many variables have been demonstrated to be associated with leukemia relapse.In this st...Background:For patients with B cell acute lymphocytic leukemia(B-ALL)who underwent allogeneic stem cell transplantation(allo-SCT),many variables have been demonstrated to be associated with leukemia relapse.In this study,we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.Methods:A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People’s Hospital from December 2010 to December 2015 were enrolled in this retrospective study.We aimed to evaluate the factors associated with transplant outcomes after allo-SCT,and establish a risk score to identify patients with different probabilities of relapse.The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.Results:All patients achieved neutrophil engraftment,and 95.4%of patients achieved platelet engraftment.The 5-year cumulative incidence of relapse(CIR),overall survival(OS),leukemia-free survival(LFS),and non-relapse mortality were 20.7%,70.4%,65.6%,and 13.9%,respectively.Multivariate analysis showed that patients with positive post-transplantation minimal residual disease(MRD),transplanted beyond the first complete remission(≥CR2),and without chronic graft-versus-host disease(cGVHD)had higher CIR(P<0.001,P=0.004,and P<0.001,respectively)and worse LFS(P<0.001,P=0.017,and P<0.001,respectively),and OS(P<0.001,P=0.009,and P<0.001,respectively)than patients without MRD after transplantation,transplanted in CR1,and with cGVHD.A risk score for predicting relapse was formulated with the three above variables.The 5-year relapse rates were 6.3%,16.6%,55.9%,and 81.8%for patients with scores of 0,1,2,and 3(P<0.001),respectively,while the 5-year LFS and OS values decreased with increasing risk score.Conclusion:This new risk score system might stratify patients with different risks of relapse,which could guide treatment.展开更多
BACKGROUND Myelodysplastic syndromes(MDSs)are a group of hematological diseases caused by expansion of an abnormal clone of hematopoietic stem cells.Primary MDS is a potentially premalignant clonal disorder that may p...BACKGROUND Myelodysplastic syndromes(MDSs)are a group of hematological diseases caused by expansion of an abnormal clone of hematopoietic stem cells.Primary MDS is a potentially premalignant clonal disorder that may progress to overt acute leukemia in 25%-50%of cases.However,most of these cases evolve into acute myeloid leukemia and rarely progress to acute lymphoblastic leukemia(ALL).Thus,transformation of MDS into B-cell ALL is rare.CASE SUMMARY A 58-year-old man was admitted to the hospital for reduced blood cell counts.Based on all the test results and the World Health Organization diagnosis and classification,the patient was finally diagnosed with ring-shaped sideroblastic MDS with refractory hemocytopenia due to multilineage dysplasia.We used red blood cell transfusions and other symptomatic support treatments.After 4 years,the patient felt dizziness,fatigue,and night sweats.We improved bone marrow and peripheral blood and other related auxiliary examinations.He was eventually diagnosed with B-lineage acute lymphocytic leukemia(MDS transformation).CONCLUSION The number of peripheral blood cells,type of MDS,proportion of primitive cells in bone marrow,and number and quality of karyotypes are all closely related to the conversion of MDS to ALL.展开更多
Objective To evaluate the outcome of combination of intensive preconditioning regimen allo - HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia ( ALL) . Methods Between 2009 and 2010,...Objective To evaluate the outcome of combination of intensive preconditioning regimen allo - HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia ( ALL) . Methods Between 2009 and 2010,8 patients diagnosed as Ph + ALL received展开更多
T cell receptor TCR γ gene rearrangement in a series of acute lymphocytic leukemia (ALL) patients was studied using PCR technique. 18 V-J junctional sequences (designated by N sequence) of TCR γ gene were amplified ...T cell receptor TCR γ gene rearrangement in a series of acute lymphocytic leukemia (ALL) patients was studied using PCR technique. 18 V-J junctional sequences (designated by N sequence) of TCR γ gene were amplified with the Vγ and Jγ primers, using an unsymmetrical PCR and analysed by direct sequencing, demonstrating that in Chinese ALLs, the N sequences of TCR Y gene are indeed clone-specific. Based on the known N sequences, several oligo-nucleotides were sythesized as probes, which were specific for the leukemic clone, and were used to detect the minimal residual disease (MRD) in 4 ALL cases. The sensitivity of this method was 0.1%-0.01%.展开更多
To the Editor: Infection is one of the causes of death after chemotherapy in children with leukemia. About 20% to 30% acute lymphocytic leukemia (ALL) patients die from infection after chemotherapy.[1] Patients with i...To the Editor: Infection is one of the causes of death after chemotherapy in children with leukemia. About 20% to 30% acute lymphocytic leukemia (ALL) patients die from infection after chemotherapy.[1] Patients with immune deficiency, under chemotherapy, or treated with immunosuppressor are more inclined to be infected with human cytomegalovirus (HCMV) which leads to severe systematic disorders.[2] Cytomegalvirus retinitis (CMVR) is a major sight threatening disease which mainly occurs in patients with immune deficiency and results in blindness if treatment is delayed. The decrease of CD4+ T cells has been related to CMVR in immune deficiency syndrome like AIDS.[3] However, little is known about the relation between the level of T cells with different markers and the onset of CMVR in ALL patients under chemotherapy. Therefore, this study was designed to investigate the diagnostic value of T cells with different markers for cytomegalovirus retinitis after chemotherapy in patients with ALL.展开更多
Objective To investigate the relationship between cytochrome P4501A1 (CYPIA1) Msp I gene polymorphism and childhood acute leukemia (AL). Methods Relevant literature was extensively searched and screened by Pubmed ...Objective To investigate the relationship between cytochrome P4501A1 (CYPIA1) Msp I gene polymorphism and childhood acute leukemia (AL). Methods Relevant literature was extensively searched and screened by Pubmed and Wanfang Database, Chinese Science Journal Database and Chinese Journal Net. Various data consolidation, combined OR values and their 95% CI were tested by RevMan 4.2; Funnel plots were used for the bias analysis. Results Six related literatures were found to meet the requirements. According to heterogeneity results, there was no significant difference in homozygous types(P〉0.05), while there was significant difference in two others types (P all〈0.05). For wild CYPIAIMspl homozygous for the reference group, Combined OR of heterozygous mutation, homozygous, heterozygous + homozygous mutation in AL and control groups were 1.18, 0.96, and 1.10 respectively. Subgroup analysis: Z values of CYP1A1Mspl homozygous, heterozygous + homozygous in the acute lymphoblastic leukemia (ALL) and the control group were 0.10 and 0.76 respectively, Z values in non-acute lymphoblastic leukemia and control group were 0.74 and 0.75. Conclusion There is no correlation between CYP1A1Mspl gene polymorphism and the susceptibility of childhood AL.展开更多
Acute Myeloid Leukemia (AML) is a group of genetically diverse hematopoietic malignancies arising from cell progenitors developing in the myeloid pathway or from primitive stem cells. Genetic susceptibility of AML may...Acute Myeloid Leukemia (AML) is a group of genetically diverse hematopoietic malignancies arising from cell progenitors developing in the myeloid pathway or from primitive stem cells. Genetic susceptibility of AML may account for an increased risk of AML due to partial metabolism of or biocativation of carcinogens. Chemical compounds are metabolized by a two-tiered phase detoxifying system. Polymorphisms in these pathways may lead to DNA damage and development of AML. We determined the frequencies of carcinogen metabolism gene polymorphisms (CYP1A1, del{GSTM1} and del{GSTT1}) in a case control-study based on polymorphism analysis. Fifty-eight consecutively AML patients (median age 62 years) and 174 sex and age-matched control group were assessed by a PCR-RFLP assay. There were 51 de novo and 7 secondary AML. CYP1A1*2A and CYP1A1*2C polymorphisms were more frequent in CG than AML p 0.001 and in contrast, CYP1A1*3 and CYP1A1*4 were more frequent in AML than CG p 0.001. There were no differences in del{GSTM1} neither del{GSTT1} between AML and CG (p = 0.999 and p = 0.539). Odds ratio for AML in patients harboring CYP1A1*3 was 2.36 (95% CI 1.2 - 4.5), 2.38 for CYP1A1*4 (95% CI 0.8 - 6.8). Adjusted OR was 2.63 for CYP1A1*3 (95% CI 1.4 - 5.1) and 2.66 for CYP1A1*4 (95% CI 0.9 - 7.8). In the multivariate analysis CYP1A1*3 polymorphism was a risk factor for AML with an OR for 3.99 (95%CI 1.9 - 8.6). To the best of our knowledge this is the first study to show that CYP1A1*3 heterozygous genotypes increase the risk of AML. Our data support that inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.展开更多
The peripheral blood lymphocyte chromosomes in a case of 60Co γ rays accident were examined at 2.5h after exposure. The frequency of the dicentrics plus centric rings was 89% and exposure dose was estimated to be 4.7...The peripheral blood lymphocyte chromosomes in a case of 60Co γ rays accident were examined at 2.5h after exposure. The frequency of the dicentrics plus centric rings was 89% and exposure dose was estimated to be 4.78 (4.53~4.88) Gy. The examinations of lymphocyte chromosome aberration within follow-up 12α showed that the incidence of Dic+R reduced with lg regression (r = -0.9895). While the number of cells with stable aberration remained unchanged and showed a tendency to increase. During the period of leukemia, bone marrow cell chromosome aberrations were studied by method of G-banding. Of 13 cells observed, 4 cells belonged to normal karyotypes. Among 9 aberration cells, 12 aberrations were detected. The majority of which were classified as translocation, deletion and inversion. Numeric aberrations were-9,-12,-20,-22,-y. This case suggested that acute lymphocytic leukemia was induced after radiation accident.展开更多
Background Immunoglobulin heavy chain variable region (IgHV) is a well-characterized tumor antigen for B-cell malignancies. It can function as a target for T cell-mediated immune response. Clinical trials of IgHV pr...Background Immunoglobulin heavy chain variable region (IgHV) is a well-characterized tumor antigen for B-cell malignancies. It can function as a target for T cell-mediated immune response. Clinical trials of IgHV protein vaccines against lymphoma have demonstrated induction of tumor-specific cytotoxic T lymphocyte (CTL) responses. However, complementary determining regions-based individual vaccines have disadvantages for wide clinical application. Although a recent study demonstrated that immunogenic peptides are derived from framework regions (FR) shared among patients with B-cell lymphoma, how to choose the appropriate peptides for each patient is still unsolved. The aim of this study was to investigate whether immunoglobulin heavy chain FR-derived peptides shared in each IgHV family are potential CTL epitopes presented by B-cell acute lymphoblastic leukemia (B-ALL). Such CTL epitopes might be beneficial to shifting vaccination strategies against B-ALL from individual specificity to family specificity.Methods Seven IgHV gene families were amplified respectively by PCR and sequenced directly from 71 childhood B-ALL cases. Bioinformatics was applied in analyzing characteristics of sequences available and predicting HLA-A^*0201-restricted CTL epitopes for each IgHV family. An antigen-specific T cell expansion system was used to generate peptide-specific CTLs. The cytotoxicity of CTLs against B-ALL cells was assessed in the lactate dehydrogenase release assay. Results Complete IgHV rearrangements were identified in all of the 71 B-ALL cases. All of 40 sequences available showed ≥98% homology with the nearest germline IgHV genes, indicating IgHV genes in B-ALL of germline nature. Twelve nonapeptides of high HLA-A^*0201-binding scores were obtained from 26 productive IgHV protein sequences. Ten (83%) of the peptides were located in FR1 and FR3 shared among the corresponding IgHV family. CTLs specific for the peptide QLVQSGAEV located in FR1 (3-11) shared among the IgHV1 family could be successfully generated from peripheral blood mononuclear cells of two HLA-A^*0201+ healthy donors in vitro and were capable of killing HLA-matched B-ALL cell clones belonging to the IgHV1 family. Conclusion Anti-B-ALL CTLs against immunoglobulin heavy chain FR-derived peptides have family-specific cytotoxicity.展开更多
文摘The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By taking these factors into account, the study aims to explore how existing cancer registry data can aid in the early detection and effective treatment of ALL in patients. Our hypothesis was that statistically significant correlations exist between race, age at which patients were diagnosed, sex, and phenotype of the ALL patients, and their rate of incidence and survivability data were evaluated using SEER*Stat statistical software from National Cancer Institute. Analysis of the incidence data revealed that a higher prevalence of ALL was among the Caucasian population. The majority of ALL cases (59%) occurred in patients aged between 0 to 19 years at the time of diagnosis, and 56% of the affected individuals were male. The B-cell phenotype was predominantly associated with ALL cases (73%). When analyzing survivability data, it was observed that the 5-year survival rates slightly exceeded the 10-year survival rates for the respective demographics. Survivability rates of African Americans patients were the lowest compared to Caucasian, Asian, Pacific Islanders, Alaskan Native, Native Americans and others. Survivability rates progressively decreased for older patients. Moreover, this study investigated the typical treatment methods applied to ALL patients, mainly comprising chemotherapy, with occasional supplementation of radiation therapy as required. The study demonstrated the considerable efficacy of chemotherapy in enhancing patients’ chances of survival, while those who remained untreated faced a less favorable prognosis from the disease. Although a significant amount of data and information exists, this study can help doctors in the future by diagnosing patients with certain characteristics. It will further assist the health care professionals in screening potential patients and early detection of cases. This could also save the lives of elderly patients who have a higher mortality rate from this disease.
文摘BACKGROUND The concurrence of acute myeloid leukemia(AML)and chronic lymphocytic leukemia(CLL)is rare.Previous reports of such cases have focused mainly on clinical diagnosis and characteristics,so the mechanism remains unclear,and therapy options have been poorly explored.CASE SUMMARY Here,we report two cases of synchronous AML and CLL.Flow cytometry revealed two distinct abnormal cell populations(myeloblasts and lymphoid cells)according to scatter characteristics.CD5-positive B cell lymphoma with myeloid leukemia invasion was observed on lymph node biopsy.Chemotherapy regimens indicated for both AML and CLL were used in our patients,and our patients achieved complete response after chemotherapy.Next-generation sequencing of 88 genes was performed.CONCLUSION We conclude that early mutation and dysregulation at the hematopoietic stem cell stage and the accumulation of multiple rearrangements may cause the concurrence of CLL and AML.The treatment of infection and combination therapy aimed at the CLL component are significant in the management of patients with concurrent CLL and AML.
基金Supported by the Scientific Research Project of Peking University Shenzhen Hospital,No.JCYJ2018011the San-Ming Project of Medicine in Shenzhen,No.SZSM201812059.
文摘BACKGROUND In recent years,the rate of immunosuppressed patients has increased rapidly.Invasive fungal infections usually occur in these patients,especially those who have had hematological malignances and received chemotherapy.Fusariosis is a rare pathogenic fungus,it can lead to severely invasive Fusarium infections.Along with the increased rate of immune compromised patients,the incidence of invasive Fusarium infections has also increased from the past few years.Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection.CASE SUMMARY We report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin,eyeball,and knee joint during the course of chemotherapy.We performed skin biopsy,microbial cultivation,and molecular biological identification,and the pathogenic fungus was finally confirmed to be Fusarium solani.The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily,and surgical debridement.Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery.The disseminated Fusarium solani infection eventually resolved,and there was no recurrence at the 3 mo follow-up.CONCLUSION Our case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection.These are important to prevent progression to a more aggressive infection.Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy.Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.
文摘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 <sup>32</sup>P-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.
文摘Procaine and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemlc cells. In this study, the combined effects of procaine and hyperthermia on the growth of hematopoietic progenitors (GM-CFU) and ieukemic progenitors (L-CFU) were examined to determine if this combination resulted in a great selective killing of leukemlc cells than that achieved by procaine or heat alone. When the cells were treated simutaneously with procaine (2 mM) and hyperthermia (42℃) for one hour, the killing of L-CFU was enhanced considerably whereas GM-CFU were not markedly affected. These data Indicate that the combined treatment with procain and hyperthermia might offer an efficient mean to selectively purge residual leukemlc cells in vitro. Procaine with hyperthermia may have a role in clinical autoiogous bone marrow transplantation for acute leukemia.
文摘Objective: Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy at which short survival may be seen. Our study aims to evaluate the effect of the neutrophil-to-lymphocyte ratio (NLR) on the course of the disease, response to therapy, and overall survival (OS). Materials and Methods: A total of 124 patients followed-up with the diagnosis of AML from 2016 to 2019 were retrospectively examined. Results: 69 of the cases (55.6%) were men and 55 (44.3%) were women. The average age at the time of diagnosis was 53.44 ± 30.3 years old. We determined the NLR as median 0.46 (0.16 - 1.1). In AML, 69 patients were responsive to the induction regimen (57.9%) while 46 patients were unresponsive (37.8%). 5 patients died before completing the regimen. D-dimer was found to be higher and fibrinogen was found to be lower in the responsive group. Lower OS was observed in cases of >60 years of age, male gender, non-APL AML, high NLR, and recurrence at diagnosis. Recurrences were detected in 23 patients (18.5%) and the median time to the recurrence was 416 (236 - 639) days. Fibrinogen level and the bone marrow blast ratio at the time of application were determined to be associated with recurrence. The median follow-up time was 856 (143 - 1276) days. Final condition analysis reveals that 74 patients (59.6%) are alive. Conclusion: We determined in our study that the NLR is effective on survival. Medical literature on this subject is scanty and prospective studies with large patient groups are needed.
文摘Childhood survivors of acute lymphoblastic leukemia (ALL) are increased risk of several chronic complications, such as second cancers, pulmonary, metabolic complications and cardiovascular disease. Obesity and metabolic syndrome is one of the most common treatment related complication in children surviving cancer, which concurs with our nations childhood epidemic [1-3] Recent research has identified the role of genetics in the development of obesity and metabolic syndrome in childhood survivors of ALL. Growth hormone deficiency, Leptin regulation, fat mass obesity (FTO) gene and the insulin resistant ENPP1 variants disorders has been associated adverse effects of chemotherapeutic treatment and the cause of clinical manifestations of metabolic syndrome [4-8]. The illumination of the role of genetic variants can shed insights into obesity within high risk population, as well as, a target to prevent disease.
基金Supported by the National Natural Science Foundation of China,No.81700130Nanjing Medical University Science and Technology Development Fund.
文摘BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.
文摘AIM To examine the optimal absolute lymphocyte count(ALC) cut-off utilizing receiver operator characteristics(ROC) in addition to graft characteristics associated with early ALC recovery.METHODS Patients who received T-cell replete peripheral hematopoietic cell transplantation(HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes. RESULTS A total of 72 patients met the inclusion criteria andwere analyzed. Optimal ALC cut-off was established to be on day 14(D14) with ALC > 0.3 × 10~9/L. At 2 years, cumulative incidence of relapse was 16.9% vs 46.9%(P = 0.025) for early and delayed lymphocyte recovery cohorts, respectively. Chronic graft vs host disease was more prevalent in the early lymphocyte recovery(ELR) group at 70% vs 27%, respectively(P = 0.0006). On multivariable analysis for relapse, ELR retained its prognostic significance with HR = 0.27(0.05-0.94, P = 0.038).CONCLUSION ELR is an independent predictor for relapse in patients receiving allogeneic HCT for acute leukemia. ELR was influenced by graft characteristics particularly CD34 count.
文摘Objective To study the changes of lymphocyte subsets and regulatory T cells in peripheral blood of patients with acute leukemia(AL) and its clinical significance.Methods The different levels of peripheral blood lymphocyte subsets and regulatory T cells of 60 AL patients and 40 normal controls were detected with flow cytometry.Results Compared with the normal controls,the percentages of CD3+ T cells,CD4+ T cells,CD16+CD56+ NK cells and the ratio of CD4+ /CD8+ obviously decreased in newly diagnosed AL group(P <0.05),while their percentages of CD8+ T cells and CD19+ B cells significantly increased(P <0.01).The percentage of CD4+ T cells and the ratio of CD4+ /CD8+ in acute lymphoblastic leukemia(ALL) group were much lower than those in acute myelogenous leukemia(AML) group(P <0.01).Compared with these in control group,the proportions of CD4+ CD25high Treg cells and CD4+ CD25+ T cells in newly diagnosed AL group were significantly increased(P <0.01).Conclusion Cellular immune function is significantly abnormal in patients with AL.Compared with AML patients,ALL patients had poorer cellular immune function.The increased CD4 + CD25high Treg cells might be one of the important reasons of immunosuppression in AL.Detection of lymphocyte subsets and regulatory T cells is of clinical value on the evaluation of therapeutic effect and prognosis in AL patients.
基金the Shantou Science and Technology Planning Project of Guangdong Province,No.SFK[2019]79.
文摘BACKGROUND Acute myeloid leukemia is often associated with gene mutation or chromosome abnormality,which is an important factor affecting prognosis.The 5-year survival rate of patients with acute myeloid leukemia without hematopoietic stem cell transplantation is low.For patients who only received chemotherapy and whose first remission lasted>5 years,there are few reports of gene spectrum changes between relapse and initial diagnosis.CASE SUMMARY We report a 41-year-old woman who presented to our hospital with complaints of dizziness,poor appetite and wasting.She was diagnosed with acute myelomonocytic leukemia(M4b)with NPM1 mutation and only received chemotherapy.Her first remission lasted>5 years.New genetic variants were detected upon relapse that may have been related to relapse and chemotherapy resistance.CONCLUSION Mutations in WT1(R394fs/A387fs)/PTPN11 T73I/ETV6 S350P and JAK2 W659R may be related to relapse and chemotherapy resistance in acute myeloid leukemia.
基金supported by grants from the Beijing Municipal Science and Technology Commission(No.Z181100009618032)the National Key Research and Development Program of China(No.2017YFA0104500)+1 种基金the National Natural Science Foundation of China(Nos.81670186,82070185)the Peking University Clinical Scientist Program(No.BMU2019LCKXJ003)。
文摘Background:For patients with B cell acute lymphocytic leukemia(B-ALL)who underwent allogeneic stem cell transplantation(allo-SCT),many variables have been demonstrated to be associated with leukemia relapse.In this study,we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.Methods:A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People’s Hospital from December 2010 to December 2015 were enrolled in this retrospective study.We aimed to evaluate the factors associated with transplant outcomes after allo-SCT,and establish a risk score to identify patients with different probabilities of relapse.The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.Results:All patients achieved neutrophil engraftment,and 95.4%of patients achieved platelet engraftment.The 5-year cumulative incidence of relapse(CIR),overall survival(OS),leukemia-free survival(LFS),and non-relapse mortality were 20.7%,70.4%,65.6%,and 13.9%,respectively.Multivariate analysis showed that patients with positive post-transplantation minimal residual disease(MRD),transplanted beyond the first complete remission(≥CR2),and without chronic graft-versus-host disease(cGVHD)had higher CIR(P<0.001,P=0.004,and P<0.001,respectively)and worse LFS(P<0.001,P=0.017,and P<0.001,respectively),and OS(P<0.001,P=0.009,and P<0.001,respectively)than patients without MRD after transplantation,transplanted in CR1,and with cGVHD.A risk score for predicting relapse was formulated with the three above variables.The 5-year relapse rates were 6.3%,16.6%,55.9%,and 81.8%for patients with scores of 0,1,2,and 3(P<0.001),respectively,while the 5-year LFS and OS values decreased with increasing risk score.Conclusion:This new risk score system might stratify patients with different risks of relapse,which could guide treatment.
基金Shandong Medicine and Health Science Technology Development Plan,No.2017WSA08039Jining Key Research and Development Program,No.2018SMNS008+1 种基金Doctoral Research Startup Foundation of Jining First People’s Hospital,No.2019003and TCM Technology Development Plan,No.20190744.
文摘BACKGROUND Myelodysplastic syndromes(MDSs)are a group of hematological diseases caused by expansion of an abnormal clone of hematopoietic stem cells.Primary MDS is a potentially premalignant clonal disorder that may progress to overt acute leukemia in 25%-50%of cases.However,most of these cases evolve into acute myeloid leukemia and rarely progress to acute lymphoblastic leukemia(ALL).Thus,transformation of MDS into B-cell ALL is rare.CASE SUMMARY A 58-year-old man was admitted to the hospital for reduced blood cell counts.Based on all the test results and the World Health Organization diagnosis and classification,the patient was finally diagnosed with ring-shaped sideroblastic MDS with refractory hemocytopenia due to multilineage dysplasia.We used red blood cell transfusions and other symptomatic support treatments.After 4 years,the patient felt dizziness,fatigue,and night sweats.We improved bone marrow and peripheral blood and other related auxiliary examinations.He was eventually diagnosed with B-lineage acute lymphocytic leukemia(MDS transformation).CONCLUSION The number of peripheral blood cells,type of MDS,proportion of primitive cells in bone marrow,and number and quality of karyotypes are all closely related to the conversion of MDS to ALL.
文摘Objective To evaluate the outcome of combination of intensive preconditioning regimen allo - HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia ( ALL) . Methods Between 2009 and 2010,8 patients diagnosed as Ph + ALL received
基金Project supported by the National Natural Science Foundation of China and Shanghai Natural Science Foundation.
文摘T cell receptor TCR γ gene rearrangement in a series of acute lymphocytic leukemia (ALL) patients was studied using PCR technique. 18 V-J junctional sequences (designated by N sequence) of TCR γ gene were amplified with the Vγ and Jγ primers, using an unsymmetrical PCR and analysed by direct sequencing, demonstrating that in Chinese ALLs, the N sequences of TCR Y gene are indeed clone-specific. Based on the known N sequences, several oligo-nucleotides were sythesized as probes, which were specific for the leukemic clone, and were used to detect the minimal residual disease (MRD) in 4 ALL cases. The sensitivity of this method was 0.1%-0.01%.
文摘To the Editor: Infection is one of the causes of death after chemotherapy in children with leukemia. About 20% to 30% acute lymphocytic leukemia (ALL) patients die from infection after chemotherapy.[1] Patients with immune deficiency, under chemotherapy, or treated with immunosuppressor are more inclined to be infected with human cytomegalovirus (HCMV) which leads to severe systematic disorders.[2] Cytomegalvirus retinitis (CMVR) is a major sight threatening disease which mainly occurs in patients with immune deficiency and results in blindness if treatment is delayed. The decrease of CD4+ T cells has been related to CMVR in immune deficiency syndrome like AIDS.[3] However, little is known about the relation between the level of T cells with different markers and the onset of CMVR in ALL patients under chemotherapy. Therefore, this study was designed to investigate the diagnostic value of T cells with different markers for cytomegalovirus retinitis after chemotherapy in patients with ALL.
文摘Objective To investigate the relationship between cytochrome P4501A1 (CYPIA1) Msp I gene polymorphism and childhood acute leukemia (AL). Methods Relevant literature was extensively searched and screened by Pubmed and Wanfang Database, Chinese Science Journal Database and Chinese Journal Net. Various data consolidation, combined OR values and their 95% CI were tested by RevMan 4.2; Funnel plots were used for the bias analysis. Results Six related literatures were found to meet the requirements. According to heterogeneity results, there was no significant difference in homozygous types(P〉0.05), while there was significant difference in two others types (P all〈0.05). For wild CYPIAIMspl homozygous for the reference group, Combined OR of heterozygous mutation, homozygous, heterozygous + homozygous mutation in AL and control groups were 1.18, 0.96, and 1.10 respectively. Subgroup analysis: Z values of CYP1A1Mspl homozygous, heterozygous + homozygous in the acute lymphoblastic leukemia (ALL) and the control group were 0.10 and 0.76 respectively, Z values in non-acute lymphoblastic leukemia and control group were 0.74 and 0.75. Conclusion There is no correlation between CYP1A1Mspl gene polymorphism and the susceptibility of childhood AL.
基金supported by the grant providedby CNPq(Conselho Nacional de Desenvolvimento Científico e Tecnológico).The fellowship grant supported by CNPq was Luís Arthur Flores Pelloso,process number 140232/2001-0,period 03/01/2001 to 02/28/2005.
文摘Acute Myeloid Leukemia (AML) is a group of genetically diverse hematopoietic malignancies arising from cell progenitors developing in the myeloid pathway or from primitive stem cells. Genetic susceptibility of AML may account for an increased risk of AML due to partial metabolism of or biocativation of carcinogens. Chemical compounds are metabolized by a two-tiered phase detoxifying system. Polymorphisms in these pathways may lead to DNA damage and development of AML. We determined the frequencies of carcinogen metabolism gene polymorphisms (CYP1A1, del{GSTM1} and del{GSTT1}) in a case control-study based on polymorphism analysis. Fifty-eight consecutively AML patients (median age 62 years) and 174 sex and age-matched control group were assessed by a PCR-RFLP assay. There were 51 de novo and 7 secondary AML. CYP1A1*2A and CYP1A1*2C polymorphisms were more frequent in CG than AML p 0.001 and in contrast, CYP1A1*3 and CYP1A1*4 were more frequent in AML than CG p 0.001. There were no differences in del{GSTM1} neither del{GSTT1} between AML and CG (p = 0.999 and p = 0.539). Odds ratio for AML in patients harboring CYP1A1*3 was 2.36 (95% CI 1.2 - 4.5), 2.38 for CYP1A1*4 (95% CI 0.8 - 6.8). Adjusted OR was 2.63 for CYP1A1*3 (95% CI 1.4 - 5.1) and 2.66 for CYP1A1*4 (95% CI 0.9 - 7.8). In the multivariate analysis CYP1A1*3 polymorphism was a risk factor for AML with an OR for 3.99 (95%CI 1.9 - 8.6). To the best of our knowledge this is the first study to show that CYP1A1*3 heterozygous genotypes increase the risk of AML. Our data support that inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.
文摘The peripheral blood lymphocyte chromosomes in a case of 60Co γ rays accident were examined at 2.5h after exposure. The frequency of the dicentrics plus centric rings was 89% and exposure dose was estimated to be 4.78 (4.53~4.88) Gy. The examinations of lymphocyte chromosome aberration within follow-up 12α showed that the incidence of Dic+R reduced with lg regression (r = -0.9895). While the number of cells with stable aberration remained unchanged and showed a tendency to increase. During the period of leukemia, bone marrow cell chromosome aberrations were studied by method of G-banding. Of 13 cells observed, 4 cells belonged to normal karyotypes. Among 9 aberration cells, 12 aberrations were detected. The majority of which were classified as translocation, deletion and inversion. Numeric aberrations were-9,-12,-20,-22,-y. This case suggested that acute lymphocytic leukemia was induced after radiation accident.
文摘Background Immunoglobulin heavy chain variable region (IgHV) is a well-characterized tumor antigen for B-cell malignancies. It can function as a target for T cell-mediated immune response. Clinical trials of IgHV protein vaccines against lymphoma have demonstrated induction of tumor-specific cytotoxic T lymphocyte (CTL) responses. However, complementary determining regions-based individual vaccines have disadvantages for wide clinical application. Although a recent study demonstrated that immunogenic peptides are derived from framework regions (FR) shared among patients with B-cell lymphoma, how to choose the appropriate peptides for each patient is still unsolved. The aim of this study was to investigate whether immunoglobulin heavy chain FR-derived peptides shared in each IgHV family are potential CTL epitopes presented by B-cell acute lymphoblastic leukemia (B-ALL). Such CTL epitopes might be beneficial to shifting vaccination strategies against B-ALL from individual specificity to family specificity.Methods Seven IgHV gene families were amplified respectively by PCR and sequenced directly from 71 childhood B-ALL cases. Bioinformatics was applied in analyzing characteristics of sequences available and predicting HLA-A^*0201-restricted CTL epitopes for each IgHV family. An antigen-specific T cell expansion system was used to generate peptide-specific CTLs. The cytotoxicity of CTLs against B-ALL cells was assessed in the lactate dehydrogenase release assay. Results Complete IgHV rearrangements were identified in all of the 71 B-ALL cases. All of 40 sequences available showed ≥98% homology with the nearest germline IgHV genes, indicating IgHV genes in B-ALL of germline nature. Twelve nonapeptides of high HLA-A^*0201-binding scores were obtained from 26 productive IgHV protein sequences. Ten (83%) of the peptides were located in FR1 and FR3 shared among the corresponding IgHV family. CTLs specific for the peptide QLVQSGAEV located in FR1 (3-11) shared among the IgHV1 family could be successfully generated from peripheral blood mononuclear cells of two HLA-A^*0201+ healthy donors in vitro and were capable of killing HLA-matched B-ALL cell clones belonging to the IgHV1 family. Conclusion Anti-B-ALL CTLs against immunoglobulin heavy chain FR-derived peptides have family-specific cytotoxicity.