Incidence and Survivability of Acute Lymphocytic Leukemia Patients in the United States: Analysis of SEER Data Set from 2000-2019

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.

Prognostic Value of Neutrophil to Lymphocyte Ratio in Acute Myeloid Leukemia

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.

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.

Synchronous diagnosis and treatment of acute myeloid leukemia and chronic lymphocytic leukemia:Two case reports

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.

PURGING OF ACUTE NON-LYMPHOCYTIC LEUKEMIA PROGENITORS BY PROCAINE AND HYPERTHERMIA

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.

Disseminated infection by Fusarium solani in acute lymphocytic leukemia:A case report

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.

Coexistence of diffuse large B-cell lymphoma,acute myeloid leukemia,and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient:A case report

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.

Lymphocyte recovery is an independent predictor of relapse in allogeneic hematopoietic cell transplantation recipients for acute leukemia

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.

Detection of lymphocyte subsets and regulatory T cells in peripheral blood of patients with acute leukemia and its clinical significance

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.

CENTRAL NERVOUS SYSTEM RADIOTHERAPY IN ACUTE LEUKEMIA

From Dec. 1976 through June 1986, 474 patients with acute leukemia were treated with central nervous system (CNS) irradiation for the purpose of preventing relapse of CNS leukemia. Of the whole series, whole cranial irradiation at a dosage of 24 Gy and 4-5 intrathecal instillations of methotrexate (MTX) were given in 149 patients, simple intrathecal instillation of MTX in 44 patients and high dose intravenous MTX in 5 patients; the CNS relapse rates were 4.0%, 20.5% and 40.0% respectively. It was proved by our experience that whole cranial irradiation plus intrathecal MTX is the best approach to prevention of CNS leukemia relapses.

Combined intensive preconditioning regimen allo-HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia

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

Myelodysplastic syndrome transformed into B-lineage acute lymphoblastic leukemia: A case report

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.

Therapy-related acute promyelocytic leukemia with FMS-like tyrosine kinase 3-internal tandem duplication mutation in solitary bone plasmacytoma: A case report

BACKGROUND Therapy-related acute promyelocytic leukemia(t-APL)is a rare complication observed in solitary bone plasmacytoma(SBP),and SBP after radiotherapy evolving to APL harboring the FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)mutation has never been reported.Here,we present the first case reported until now.CASE SUMMARY We describe a 64-year-old woman who presented with lumbar pain and was initially diagnosed with SBP.However,after one year of radiotherapy treatment,this patient experienced a long-standing bone-marrow-suppressive period and finally developed APL harboring the FLT3-ITD mutation,as confirmed by analyses of clinical features,bone marrow morphology,flow cytometry,cytogenetic examination,and molecular biology.On admission,the patient had disseminated intravascular coagulation and intracranial hemorrhage,and the peripheral blood and bone marrow smear displayed abundant abnormal promyelocytes.Unfortunately,she died when the definite diagnosis was made.CONCLUSION The patient with t-APL harboring FLT3-ITD mutation evolving from SBP after radiotherapy had not been reported and had poor clinical outcomes.FLT3-ITD mutation in t-APL may be a potential pathogenesis of leukemogenesis.We should consider the potential risk of secondary neoplasms in SBP patients after radiotherapy.

Donor-derived CD 19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD 19-positive B-ALL after Allogeneic Hematopoietic Stem Cell Transplantation

Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.

Computer-assisted formulas predicting cancer mortality risk after exposure to acute low dose ionizing radiation in humans

A clear relationship between dose of radiation and mortality in humans is still not known because of lack of human data that would enable to determine human tolerance in total body irradiation. Human data for analysis have been primarily from radiation accidents, radiotherapy and the atomic bomb victims. A general formula that predicts mortality probability as a function of dose rate and duration of exposure to acute high dose ionizing radiation in humans was published by the author, applying the “probacent” model to the reported data on animal-model-predicted dose versus mortality. In this study, the “probacent” model is applied to the data on dose versus cancer mortality risk, published by the United Nations (UNSCEAR, 2010) and other investigators to construct general formulas expressing a relationship between dose and solid cancer or leukemia mortality probability after exposure to acute low dose ionizing radiation in humans. There is a remarkable agreement between formula-derived and published values of dose and solid cancer or leukemia mortality probability (p > 0.99). The general formula might be helpful in preventing radiation hazard and injury in acute low dose ionizing radiation, and for safety in radiotherapy.

259例急性淋巴细胞白血病患儿化疗致肝损伤相关因素分析

目的总结儿童急性淋巴细胞白血病(Acute lymphoblastic leukemia,ALL)患者化疗后发生肝损伤的情况,研究性分析ALL患儿发生肝损伤的危险因素。方法回顾性分析2019年1月-2022年4月新疆医科大学第一附属医院儿科259例ALL患儿化疗的临床资料,对年龄、体重指数(BMI)、性别、化疗阶段、白蛋白水平、血红蛋白水平、否使用大剂量甲氨蝶呤、感染、髓外预防相关因素进行数据搜集,先单因素分析,对显著性影响的因素再采用logistic回归进行多因素分析。结果单因素分析结果表明性别、各年龄段、不同BMI、各化疗阶段及是否使用大剂量甲氨蝶呤对化疗后肝损伤的发生均不具有统计学意义(P>0.05)。鞘内注射、贫血、低蛋白血症、感染更容易发生化疗后肝损伤,差异均具有统计学意义。Logistic回归结果表明低蛋白血症是化疗后肝损伤发生的独立危险因素。结论儿童ALL化疗肝损伤的发生率与贫血、低蛋白血症、感染、髓外预防有关。低蛋白血症是化疗后肝损伤的独立影响因素,化疗前需给予适当治疗,从而降低化疗后肝损伤的发生率。

22例婴儿急性淋巴细胞白血病的临床特征及预后分析

目的 分析婴儿急性淋巴细胞白血病(IALL)的临床及生物学特点,探讨其疗效及预后相关因素。方法 回顾性分析2010年1月—2020年6月于我院初诊并进行治疗的IALL患儿22例,分析其MICM分型、转归及预后影响因素。结果 IALL占我院急性淋巴细胞白血病(ALL)总收治数的3.33%。22例IALL发病时中位年龄9(3~11)月,所有患儿均为B-ALL,10例CD10表达为阴性,12例合并MLL重排(MLLr)。诱导治疗第19天,19例(86.4%)骨髓获完全缓解。12例(54.6%)治疗期间合并严重感染,5例(22.7%)因严重感染而死亡。5例(22.7%)骨髓复发,预计3年累积复发率为29.6%±11.3%,合并MLLr患儿更易出现复发(P=0.04)。22例患儿预计3年无事件生存(EFS)率为49.0%±10.8%,预计3年总生存期(OS)率为49.7%±10.9%。初诊年龄<6月及6~12月者预计3年EFS率分别为33.3%±19.2%、54.5%±12.8%(P=0.28),CD10阴性与阳性患儿的预计3年EFS率分别为40.0%±15.5%、56.3%±14.8%(P=0.29),MLLr阳性与阴性患儿的预计3年EFS率分别为33.3%±13.6%、68.6%±15.1%(P=0.12)。结论 IALL因其特殊的临床及生物学特征,治疗相关死亡率高,复发率高,总体预后差,初诊年龄<6月龄、免疫表型CD10阴性及合并MLLr的患儿预后更差。

ALL患儿诱导缓解期长春新碱联合应用三唑类抗真菌药物发生毒副作用单中心分析

目的研究急性淋巴细胞白血病(ALL)儿童诱导缓解期联合应用长春新碱与三唑类药物出现的毒副作用。方法回顾性分析2010年1月1日—2013年12月31日北京儿童医院诊断为ALL患儿在诱导缓解治疗过程中长春新碱和三唑类药物联合应用出现毒副作用。将患儿分为无联合用药组、长春新碱+伊曲康唑联合组,长春新碱+伏立康唑联合组,长春新碱+氟康唑联合组,分析4组患儿相关毒副作用的发生率及治疗预后。结果共纳入ALL患儿708例,发病中位年龄为8(1~16)岁。存在长春新碱与三唑类抗真菌药物联合应用组共215例,其中联合伊曲康唑组79例,联合伏立康唑组36例,联合氟康唑组100例。无联合用药组493例。联合用药组患儿相关并发症发生率:高血压37例(17.2%),趾端麻木39例(18.1%),腱反射迟钝4例(1.8%),腹痛腹胀42例(19.5%),肠梗阻5例(2.3%),低血钠43例(20%)。联合用药组相关并发症发生率均高于无联合用药物组(P<0.05)。联合用药组中,高血压发生率、腱反射迟钝发生率及低血钠发生率:伊曲康唑组与伏立康唑组无差别(P>0.05),但大于氟康唑组(P<0.05);趾端麻木、腹痛腹胀发生率:伊曲康唑组大于伏立康唑组大于氟康唑组(P<0.05);肠梗阻发生率:伏立康唑组大于伊曲康唑组大于氟康唑组(P<0.05)。对于发生的毒副作用,给予相关的对症处理及调整药物后,相关并发症均可以得到缓解及消失。结论在ALL患儿诱导缓解治疗过程中,三唑类药物联合长春新碱用药可能加重毒副作用发生,伊曲康唑和伏立康唑相比氟康唑可能更容易加重长春新碱毒性,故建议治疗过程中避免同时使用三唑类抗真菌药物及长春新碱。

伊布替尼治疗慢性淋巴细胞白血病引起急性肾损伤不良反应1例

目的探讨伊布替尼致急性肾损伤的临床特征和处置措施。方法以1例伊布替尼治疗慢性淋巴细胞白血病引起急性肾损伤不良反应为切入点,检索FAERS数据库和查阅文献,分析其临床特征和处置措施。结果数据显示,伊布替尼引起急性肾损伤的发生率很低,表现为血清肌酐水平升高,可合并蛋白尿、血尿,肾活检显示为急性间质性肾炎或急性肾小管坏死。及时停药、经糖皮质激素等免疫抑制治疗后,部分患者血清肌酐水平可有所恢复。结论临床医生应权衡利弊,密切监测患者血肌酐,保障患者用药安全。

花旗松素调节MCP-1/CCR2轴对急性淋巴细胞白血病细胞恶性进展的影响

目的:研究花旗松素(Taxifolin)对急性淋巴细胞白血病(ALL)细胞恶性进展的影响及单核细胞趋化蛋白-1(CCL2)/CC趋化因子受体2(CCR2)轴发挥的作用。方法:体外培养ALL-T淋巴细胞CCRF-CEM;CCK-8法检测不同浓度Taxifolin对CCRF-CEM细胞活力影响,筛选本实验用Taxifolin浓度;将CCRF-CEM细胞分为control组、Taxifolin-L组、Taxifolin-M组、Taxifolin-H组、Taxifolin+rCCL2组;EDU法检测各组CCRF-CEM细胞增殖;流式细胞术检测各组CCRF-CEM细胞凋亡;Transwell检测各组CCRF-CEM细胞侵袭能力;平板克隆形成实验检测各组CCRF-CEM细胞集落形成能力;RT-PCR检测各组CCRF-CEM细胞CCL2、CCR2基因表达水平;Western blot检测各组CCRF-CEM细胞CCL2、CCR2、Bcl-2、Bax、Caspase-3蛋白表达水平。结果:选择25、50、100μmol/L三个Taxifolin浓度进行后续实验;与control组相比,Taxifolin-L、M、H组CCRF-CEM细胞凋亡率、Bax、Caspase-3蛋白表达水平显著升高,CCRF-CEM细胞EDU阳性细胞率、侵袭细胞数量、细胞克隆集落数、CCL2、CCR2基因表达水平、CCL2、CCR2、Bcl-2蛋白表达水平均显著性降低,且呈剂量依赖性(P<0.05);与Taxifolin-H组相比,Taxifolin+rCCL2组CCRF-CEM细胞凋亡率、Bax、Caspase-3蛋白表达水平显著性降低,CCRF-CEM细胞EDU阳性细胞率、侵袭细胞数量、细胞克隆集落数、CCL2、CCR2基因表达水平、CCL2、CCR2、Bcl-2蛋白表达水平均显著性升高(P<0.05)。结论:Taxifolin可能通过抑制CCL2/CCR2轴,从而抑制CCRF-CEM细胞恶性进展。