Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

High frequency of CD34+CD38-/low immature leukemia cells is correlated with unfavorable prognosis in acute myeloid leukemia

AIM To evaluate the importance of the CD34+CD38-cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival.METHODS Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia(AML) were studied between September 2008 and December 2010 at our Institution(Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8 C panels and FACS CANTO and Diva software(BD Bioscience).RESULTS We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38-population. Using a cut-off value of 1% of CD34+CD38-from total "bulk leukemic cells" we found that a high(> 1%) level of CD34+CD38-blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38-leukemic cells > 1% was an independent predictor of DFS [HR = 2.8(1.02-7.73), P = 0.04] and OS [HR = 2.65(1.09-6.43), P = 0.03].CONCLUSION Taken together, these results show that a CD34/CD38 "backbone" for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.

Elevated nuclear phospho-eIF4E body levels are associated with tumor progression and poor prognosis for acute myeloid leukemia

Uncontrolled proliferation is a hallmark of cancer cells,yet the molecular mechanisms that contribute to this proliferation are unclear.Therapeutic treatment of cancer is suboptimal in many cases,with no accurate index by which to evaluate the success of treatment or patient prognosis.In this study,we explored the protein levels of nuclear phospho-eIF4E in acute myeloid leukemia(AML)cell lines and primary leukemia samples by Western blot and immunofluorescence and as well analyzed transcriptomes by RNA-seq.We found nuclear phospho-eIF4E,an exporter of oncogenic mRNAs,to be abundant in AML.Further,nuclear phospho-eIF4E abundance was significantly associated with tumor burden as well as the response of AML patients to chemotherapy.The results demonstrate“massive clustering and export of oncogenic mRNAs to the translation machinery”by highly abundant RNA-nuclear phospho-eIF4E bodies.This is an efficient mechanism that may drive the proliferation of cancer cells.Herein,nuclear phospho-eIF4E bodies were identified as potential markers of AML,which may be useful for prognosis and as targets for cancer therapy.

Role of microRNA dysregulation in childhood acute leukemias:Diagnostics,monitoring and therapeutics:A comprehensive review

MicroRNAs(miRNAs)are short noncoding RNAs that regulate the expression of genes by sequence-specific binding to mRNA to either promote or block its translation;they can also act as tumor suppressors(e.g.,let-7b,miR-29a,miR-99,mir-100,miR-155,and miR-181)and/or oncogenes(e.g.,miR-29a,miR-125b,miR-143-p3,mir-155,miR-181,miR-183,miR-196b,and miR-223)in childhood acute leukemia(AL).Differentially expressed miRNAs are important factors associated with the initiation and progression of AL.As shown in many studies,they can be used as noninvasive diagnostic and prognostic biomarkers,which are useful in monitoring early stages of AL development or during therapy(e.g.,miR-125b,miR-146b,miR-181c,and miR-4786),accurate classification of different cellular or molecular AL subgroups(e.g.,let-7b,miR-98,miR-100,miR-128b,and miR-223),and identification and development of new therapeutic agents(e.g.,mir-10,miR-125b,miR-203,miR-210,miR-335).Specific miRNA patterns have also been described for commonly used AL therapy drugs(e.g.,miR-125b and miR-223 for doxorubicin,miR-335 and miR-1208 for prednisolone,and miR-203 for imatinib),uncovering miRNAs that are associated with treatment response.In the current review,the role of miRNAs in the development,progression,and therapy monitoring of pediatric ALs will be presented and discussed.

Philadelphia chromosome-positive leukemia stem cells in acute lymphoblastic leukemia and tyrosine kinase inhibitor therapy

Leukemia stem cells(LSCs),which constitute a minority of the tumor bulk,are functionally defined on the basis of their ability to transfer leukemia into an immunodeficient recipient animal.The presence of LSCs has been demonstrated in acute lymphoblastic leukemia(ALL),of which ALL with Philadelphia chromosome-positive(Ph+).The use of imatinib,a tyrosine kinase inhibitor(TKI),as part of front-line treatment and in combination with cytotoxic agents,has greatly improved the proportions of complete response and molecular remission and the overall outcome in adults with newly diagnosed Ph+ ALL.New challenges have emerged with respect to induction of resistance to imatinib via Abelson tyrosine kinase mutations.An important recent addition to the arsenal against Ph+ leukemias in general was the development of novel TKIs,such as nilotinib and dasatinib.However,in vitro experiments have suggested that TKIs have an antiproliferative but not an antiapoptotic or cytotoxic effect on the most primitive ALL stem cells.None of the TKIs in clinical use target the LSC.Second generation TKI dasatinib has been shown to have a more profound effect on the stem cell compartment but the drug was still unable to kill the most primitive LSCs.Allogeneic stem cell transplantation(SCT) remains the only curative treatment available for these patients.Several mechanisms were proposed to explain the resistance of LSCs to TKIs in addition to mutations.Hence,TKIs may be used as a bridge to SCT rather than monotherapy or combination with standard chemotherapy.Better understanding the biology of Ph+ ALL will open new avenues for effective management.In this review,we highlight recent findings relating to the question of LSCs in Ph+ ALL.

PROGNOSTIC SIGNIFICANCE OF EXPRESSION OF SURVIVIN IN ACUTE LEUKEMIA

Objective: To investigate the expression of survivin gene and its significance in acute leukemia. Methods: The expression of surviving in 134 acute leukemia patients and 4 leukemia cell lines was detected by RT-PCR and immunofluorescence analysis. Results: We detected survivin expression in 78 of 134 acute leukemia patients and all the cell lines but not in normal controls and anemia patients. Survivin gene expression correlated with a lower white blood cell count, which was 11×109/L and 48×109/L in the positive and negative group respectively (P<0.01 by the Mann-Whitney test). In 55 cases of FAB M1/M2/M3, it was associated with leukemic cell maturation(P<0.01 by the Fisher test). Survivin expression was strongly related to survival time of acute leukemia patients (P<0.05). Conclusion: These data suggest that survivin expression may be considered as a new unfavorable prognostic factor for acute leukemia due to its important role in apoptosis inhibition that influences disease outcome.

Easily manageable prognostic factors in 152 Chinese elderly acute myeloid leukemia patients:a single-center retrospective study

We retrospectively investigated the prognostic factors of acute myeloid leukemia（AML） in 152 Chinese patients with de novo AML who were older than 60 years of age and who received treatment at our hospital.Log-rank test showed that 6 parameters including older age,higher white blood cell（WBC） counts,lactate dehydrogenase（LDH）and bone marrow（BM） blasts at diagnosis,unfavorable risk cytogenetics,and non-mutated CEBPα were significant adverse prognostic factors of overall survival（OS） for elderly AML patients（P = 0.0013,0.0358,0.0132,0.0242,0.0236 and 0.0130,respectively）.Moreover,older age and higher LDH were significant adverse predictors for relapse-free survival（RFS）（P = 0.0447 and 0.0470,respectively）.Univariate analysis revealed similar results for OS to those of the log-rank test and only higher LDH at diagnosis was a significant adverse predictor for RFS（P = 0.028,HR：1.979,95%CI：1.075-3.644）.In multivariate analysis,we identified 2 trends towards independent prognostic factors for OS,including BM blasts at diagnosis（P = 0.057,HR：1.676,95%CI：0.984-2.854）and mutation status of CEBPα（P = 0.064,HR：4.173,95%CI：0.918-18.966）.Our data indicated that older age,gender and a previous history of hematologic diseases resulted in lower complete remission rate（P = 0.012,0.051 and 0.086,respectively）.We further developed an easy scoring system for predicting prognosis and response to induction therapy in older AML patients.Patients who had lower scores showed significantly longer OS and RFS（P = 0.0006 and 0.1001,respectively） and higher CR rate（P = 0.014）.Our research is limited by its retrospective nature and the results from our study need to be further validated by prospective randomized clinical trials.

Targeting leukemia stem cells:The new goal of therapy in adult acute myeloid leukemia

The most popular view of hematopoietic cell lineage organization is that of complex reactive or adaptative systems.Leukemia contains a subpopulation of cells that display characteristics of stem cells.These cells maintain tumor growth.The properties of leukemia stem cells indicate that current conventional chemotherapy, directed against the bulk of the tumor,will not be effective.Leukemia stem cells are quiescent and do not respond to cell cycle-specific cytotoxic agents used to treat leukemia and thus contribute to treatment failure. New strategies are required that specifically target this malignant stem cell population.

Trisomy 21 with t(5; 11) Chromosomal Translocation as New Unfavorable Cytogenetic Abnormalities in Pediatric Acute Myeloid Leukemia Type M2: One Case Report of Nine-year Follow-up and Literature Review

We report one case of pediatric acute myeloid leukemia type 2（AML-M2） who presented with karyotypic aberration of trisomy 21 with the t（5;11） chromosomal translocation. The patient achieved complete remission after two cycles of chemotherapy of daunorubicin, cytarabine and etoposide. Then, follow-up cytogenetic analysis from bone marrow cell cultures demonstrated a normal karyotype of 46, XY. After 9 years, the patient relapsed and the karyotypic abnormalities of trisomy 21 with t（5;11） reappeared. It was concluded that trisomy 21 with t（5; 11） is a new unfavorable cytogenetic aberration in AML-M2.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

Expression and clinical significance of CANX in acute myeloid leukemia based on TCGA database

Objective:To explore relationships between CANX expression,prognosis and immune infiltration of acute myeloid leukemia(AML)patients.Methods:The TIMER database was used to compare the CANX expression among a variety of TCGA tumor and normal tissue samples.The difference of CANX expression between AML and normal samples was found by R software.The Kaplan-Meier method and Log-Rank test were used to assess the relationship between CANX expression and patient survival.The R software was used to find correlations between CANX expression,clinical characteristics,drug sensitivity,and immune infiltration in AML.Results:The differential expression of CANX in 13 tumor and normal tissue samples were statistically significant(P<0.05).The high CANX expression was associated with a favorable prognosis(P<0.05),which was validated in GSE37642.The expression of CANX was correlated with age,survival status,FAB stage,and karyotype(P<0.05).High CANX expression,low age and favorable karyotype were independent predictors of a favorable prognosis(P<0.05).CANX expression may affect the sensitivity of AML patients to multiple drugs(P<0.05).The expression of CANX was positively correlated with that of M1 macrophages and CD8 T cells.Conclusion:CANX may be used as a novel potential biomarker,and could benefit AML patients by predicting patient prognosis and providing precise treatment indications.

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.

Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine

Background:Acute myeloid leukemia(AML)is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers.Decitabine,a deoxyribonucleic acid(DNA)methyltransferase(DNMT)in-hibitor,combined with cytarabine,aclarubicin hydrochloride,and granulocyte colony-stimulating factor(DCAG),has been used in patients newly diagnosed with AML.This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities,as well as those with specific gene mutations.However,the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined.Therefore,this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML.Methods:This study analyzed the clinical data and genetic mutations based on next-generation sequencing(NGS)in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army(PLA)General Hospital from January 2008 to August 2020.Factors associated with the cumulative incidence of relapse(CIR)and leukemia-free survival(LFS)in patients newly diagnosed with AML were analyzed.Results:The most adverse prognosis of DCAG-treated patients was observed in those with FLT3-ITD,KIT,PTPN11,GATA2,or IDH1 mutations during univariable analysis,whereas PTPN11 mutation was solely significant in multivariable analysis,with an increased likelihood of CIR(P=0.001)and reduced LFS duration(P=0.077).Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk(P=0.044)and decreased LFS duration(P=0.042)in multivariable analysis.In this study,we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range.Conclusion:NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations,indicating the need for new therapies that target this high-risk subtype of AML.These results offer a potential molecular stratification and treatment guidance for patients with AML.

Effect and Prognostic Analysis of Treatment for Acute Myeloid Leukemia Using Chinese Drugs Combined with Chemotherapy

Objective:To observe the clinical efficacy of Chinese drugs combined with chemotherapy in the treatment of acute myeloid leukemia(AML) and to investigate the prognostic relevance of the main parameters in AML treated with integrative medicine.Methods:Forty AML patients hospitalized at the authors hospital were treated with Chinese drugs and chemotherapy.The routine examination,immunophenotype and karyotype analyses were carried out.The clinical efficacy was observed and the prognostic factors were analyzed...

Early T-cell precursor leukemia:a subtype of high risk childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia includes T-cell acute lymphoblastic leukemia(T-ALL)and B-cell acute lymphoblastic leukemia(B-ALL).In children,T-ALL usually has a worse prognosis than B-ALL,although childhood T-ALL prognoses have improved remarkably.The varying outcomes among T-ALL cases suggest that an unrecognized biological heterogeneity may contribute to chemo-resistance.Deep exploration of T-lymphocyte development in recent years has found a subgroup of patients with a phenotype that resembles early T-cell precursor,which confers a much poorer prognosis than any other form of T-ALL.This novel subtype of T-ALL was called early T-cell precursor acute lymphoblastic leukemia(ETP-ALL).Flow cytometry data from T-ALL patients enrolled in Shanghai Children’s Medical Center between July 2002 and October 2010 were assessed according to Dr.Campana’s protocol.Among total 89 T-ALL cases,74 cases had enough immunophenotype data available to differentiate between ETP(CD1a^(-),CD8^(-),CD5^(dim),at least one marker of stem cell or myeloid lineage)and non-ETP.From these 74 subjects,12 ETP-ALL cases(16.2%)were identified.The event-free survival(EFS)rate at 66.8 months was 11.1%±10.1% for ETP-ALL and 57.6%±5.6% for non-ETP-ALL(P=0.003).The overall survival rates were 13.3%±11.0% for ETP-ALL and 64.7%±6.3% for non-ETP-ALL(P=0.002).Our findings demonstrate that early T-cell precursor leukemia is a very high-risk subtype of acute lymphoblastic leukemia with poor prognosis.

FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics

Mutations of fins-like tyrosine kinase 3 （FLT3） and nucleophosmin （NPM1） exon 12 genes are the most common abnormalities in adult acute myeloid leukemia （AML） with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction （PCR） and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication （FLT3/ITD） and exon 12 of the NPM1 gene. FLT3/ITD mutation was detected in 15 （19.7%） of 76 subjects, and NPM1 mutation in 20 （26.3%） subjects. Seven （9.2%） cases were positive for both FLT3/ITD and NPM1 mutations Significantly more FLT3/ITD aberration was detected in subjects with French-American-British （FAB） M1 （42.8%）. NPM1 mutation was frequently detected in subjects with M5 （47.1%） and infrequently in subjects with M2 （11.1%）. FLT3 and NPM1 mutations were significantly associated with a higher white blood cell count in peripheral blood and a lower CD34 antigen expression, but not age, sex, or platelet count. Statistical analysis revealed that the FLT3/ITD- positive group had a lower complete remission （CR） rate （53.3% vs. 83.6%）. Survival analysis showed that the FLT3/ITD-positive/NPM1 mutation-negative group had worse overall survival （OS） and relapse-free survival （RFS）. The FLT3/ITD-positive/NPM1 mutation-positive group showed a trend towards favorable survival compared with the FLT3/ITD-positive/NPM1 mutation-negative group （P=0.069）. Our results indicate that the FLT3/ITD mutation might be a prognostic factor for an unfavorable outcome in Chinese AML subjects with normal cytogenetics, while NPM1 mutation may be a favorable prognostic factor for OS and RFS in the presence of FLT3/ITD.

Prognostic significance of cytokine receptor-like factor 2 alterations in acute lymphoblastic leukemia:a meta-analysis

Background:Cytokine receptor-like factor 2(CRLF2)has been shown to play a role in the pathogenesis of acute lymphoblastic leukemia(ALL).Studies have examined the relationship between CRLF2 alterations such as over-expression or deregulation and clinical outcome in childhood ALL,but the results are conflicting.This meta­analysis aimed to explore the association between CRLF2 alterations and survival of pediatric patients with ALL.Methods:Electronic databases updated to March 2014 were searched for relevant studies.A meta-analysis was made of twelve studies including 5945 patients to evaluate the prognostic significance of CRLF2 alterations on survival in childhood ALL.Hazards ratios(HRs)with 95%confidence intervals(CIs)were pooled across the studies using a fixed-effects model.Results:CRLF2 over-expression in childhood ALL was associated with poor prognosis in terms of relapse-free survival(RFS;HR=1.70,95%CI=1.28-2.24,P=0.000),event-free survival(EFS;HR=1.78,95%CI=1.05-3.01,R=0.032),and overall survival(OS;HR=2.28,95%CI=1.42-3.65,R=0.001).The combined data also suggested that CRLF2 deregulation in childhood ALL was correlated with poor EFS(HR=1.95,95%CI=1.46-2.61,R=0.000),RFS(HR=2.20,95%CI=1.53-3.18,P=0.000),and OS(HR=1.89,95%CI=1.24-2.87,P=0.003).Subgroup analysis on multivariate HRs showed that CRLF2 deregulation independently predicted a poor prognosis for childhood ALL.Conclusions:The present meta-analysis reveals that both CRLF2 over-expression and deregulation are associated with poor prognosis in pediatric patients with ALL.

E-26 Transformation-specific Related Gene Expression and Outcomes in Cytogenetically Normal Acute Myeloid Leukemia： A Meta-analysis

Background： The E-26 transformation-specific related gene （ERG） is frequently expressed in cytogenetically normal acute myeloid leukemia （CN-AML）. Herein, we performed a meta-analysis to investigate the relationship between the prognostic significance of ERG expression and CN-AML. Methods： A systematic review of PubMed database and other search engines were used to identify the studies between January 2005 and November 2016. A total of 667 CN-AML patients were collected from seven published studies. Of the 667 patients underwent intensive chemotherapy, 429 had low expression of ERG and 238 had high expression of ERG. Summary odds ratio （OR） and the 95% confidence interval （（~7） for the ERG expression and CN-AML were calculated using fixed- or random-effects models. Heterogeneity was assessed using Chi-squared-based Q-statistic test and/2 statistics. All statistical analyses were performed using R.3.3.1 software packages （R Foundation for Statistical Computing, Vienna, Austria） and RevManS.3 （Cochrane Collaboration, Copenhagen, Denmark）. Results： Overall patients with high ERG expression had a worse relapse （OR = 2.5127. 95% CI： 1.5177-4.1601, P = 0.0003） and lower complete remission （OR = 0.3495, 95% CI： 0.2418-0.5051, P 〈 0.0001）. With regard to the known molecular markers, both internal tandem duplications of the fms-related tyrosine kinase 3 gene （OR =3.8634, 95% CI： 1.8285-8.1626, P = 0.004） and brain and acute leukemia, cytoplasmic （OR = 3.1538, 95% CI： 2.0537-4.8432, P 〈 0.0001） were associated with the ERG expression. In addition, the results showed a statistical significance between French-American-British （FAB） classification subtype （minimally differentiated AML and AML without maturation, OR = 4.7902, 95% CI： 2.7772-8.2624, P 〈 0.0001; acute monocytic leukemia, OR = 0.2324, 95% CI： 0.0899-0.60（/6, P = 0.0026） and ERG expression. Conclusion： High ERG expression might be used as a strong adverse prognostic factor in CN-AML.

FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

Fibroblast growth factor 13(FGF13)is aberrantly expressed in multiple cancer types,suggesting its essential role in tumorigenesis.Hence,we aimed to explore its definite role in the development of acute myeloid leukemia(AML)and emphasize its associations with bone marrow niches.Results showed that FGF13 was lowly expressed in patients with AML and that its elevated expression was related to prolonged overall survival(OS).Univariate and multivariate Cox regression analyses identified FGF13 as an independent prognostic factor.A prognostic nomogram integrating FGF13 and clinicopathologic variables was constructed to predict 1-,3-,and 5-year OS.Gene mutation and functional analyses indicated that FGF13 was not associated with AML driver mutations but was related to bone marrow niches.As for immunity,FGF13 was remarkably associated with T cell count,immune checkpoint genes,and cytokines.In addition,FGF13 overexpression substantially inhibited the growth and significantly induced the early apoptosis of AML cells.The xenograft study indicated that FGF13 overexpression prolonged the survival of recipient mice.Overall,FGF13 could serve as an independent prognostic factor for AML,and it was closely related to the bone marrow microenvironment.

PTPN11基因突变急性髓系白血病患者临床特征及预后分析

目的 探讨PTPN11基因突变急性髓系白血病(AML)患者的临床特征及预后情况。方法 选取经医院初次诊断、治疗并行二代测序(NGS)检测的成人AML患者115例,收集包括疾病特征、治疗效果、长期预后、免疫细胞亚群以及白血病干细胞等数据,分析PTPN11基因突变AML患者的临床特征及预后情况。结果 初诊成人AML中PTPN11基因突变率为9.57%,突变位点主要发生在3号外显子区域,突变类型均为点突变。与PTPN11基因野生型组相比,PTPN11基因突变组首次诱导治疗期间早期病死率高(18.18%vs 4.00%,P=0.048),完全缓解率低(33.33%vs 67.71%,P=0.039),复发率高(83.33%vs 42.31%,P=0.043),中位总生存时间短(9月vs 20月,P=0.026),效应性T细胞比例低[(1.39±0.12)%vs(3.56±0.46)%,P=0.038],白血病干细胞比例高[(13.82±3.66)%vs(3.87±1.40)%,P=0.021]。结论 PTPN11基因突变是AML的不良预后标志物,该类患者早期病死率高、完全缓解率低、复发率高、中位总生存时间短,且体内效应性T细胞比例低、白血病干细胞比例高。