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.

Myeloid sarcoma with maxillary gingival swell

BACKGROUND Myeloid sarcoma(MS),also referred to as granulocytic sarcoma or chloroma,is a rare type of extramedullary malignant tumor.MS comprises primitive granulocytic precursor cells that play a key role in the early stages of white blood cell development.Notably,the occurrence of this tumor in the gingiva is rare.CASE SUMMARY The present study reported the case of MS with gingival swelling in the maxillary region,with aleukemic presentation in a 32-year-old male patient.Following two courses of chemotherapy,computed tomography of the region demonstrated complete clearance of the tumor.At the 12-month follow-up appointment,the patient was in a stable condition with the absence of progression.The etiology,clinical features,diagnosis,and relevant treatment of MS are discussed in the present study.CONCLUSION Diagnosis of MS may be confirmed following histological and immunohistochemical examinations.

Diagnostic and therapeutic challenges of myeloid sarcoma in the oral cavity

Myeloid sarcoma(MS)is a rare neoplasm characterized by the proliferation of immature myeloid precursor cells outside the bone marrow.The pathogenesis of MS is complex and not completely understood.Moreover,it develops in any extramedullary site of the body.In this editorial,we discuss the article published by Li et al,which presents a clinical case involving a 32-year-old man who exhibited gingival inflammation in the maxillary region.It was initially diagnosed as periodontal disease.However,clinical evaluation revealed a firm,grayishwhite mass which underscored the need for comprehensive diagnostics to distinguish MS from other oral conditions.This article emphasizes the different clinical presentations of similar case studies in the literature,and highlights the difficulty in diagnosing oral MS due to its rarity and variability in clinical manifestation.The treatment of MS depends on the clinical presentation,tumor location,and the patient's response to conventional therapies.The various therapeutic options currently available are analyzed and discussed.Early intervention and multidisciplinary management are crucial for improving treatment outcomes.Increased awareness and education about the various clinical presentations of MS lead to earlier diagnosis and timely treatment,thereby enhancing patients'survival and quality of life.Continued research is essential for optimizing therapeutic strategies and addressing the challenges presented by this rare neoplasm.

Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia

Objective The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid proliferation.This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells.Methods SKM-1 cells(an AML cell line)were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide(BPTES,a glutaminase inhibitor)or cytarabine.Cell viability was detected by Cell Counting Kit-8(CCK-8)assay,and cell apoptosis and reactive oxygen species(ROS)by flow cytometry.Western blotting was conducted to examine the levels of apoptotic proteins,including cleaved caspase-3 and poly(ADP-ribose)polymerase(PARP).Moreover,the human long noncoding RNA(lncRNA)microarray was used to analyze gene expression after glutamine deprivation,and results were confirmed with quantitative RT-PCR(qRT-PCR).The expression of metallothionein 2A(MT2A)was suppressed using siRNA.Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry,respectively,in cells with MT2A knockdown.Results Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells.The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation.MT2A knockdown increased apoptosis,while proliferation was not affected in SKM-1 cells.In addition,metformin inhibited cell growth and induced apoptosis in SKM-1 cells.Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine.Furthermore,the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells.Conclusion Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

Adult rhabdomyosarcoma combined with acute myeloid leukemia: A case report

BACKGROUND Rhabdomyosarcoma is a tumor of mesenchymal origin.Secondary leukemia is a complication of previous transformation to other hematologic disorders or is a treatment-related acute myeloid leukemia secondary to cytotoxic chemotherapy or radiation therapy for other malignancies.CASE SUMMARY We present the case of a 36-year-old female patient who was diagnosed with rhabdomyosarcoma and acute myeloid leukemia.Further disease progression was observed after multiline chemotherapy.Eventually,the patient suffered cerebral hemorrhage,which resulted in death.CONCLUSION The incidence of rhabdomyosarcoma in adults is extremely low,and secondary leukemia caused by rhabdomyosarcoma is even rarer.Secondary leukemia has a very poor prognosis and a low overall survival rate.

Targeting nuclear factor erythroid 2-related factor 2-regulated ferroptosis to treat nervous system diseases

By critically examining the work,we conducted a comprehensive bibliometric analysis on the role of nuclear factor erythroid 2-related factor 2(NRF2)in nervous system diseases.We also proposed suggestions for future bibliometric studies,including the integration of multiple websites,analytical tools,and analytical approaches,The findings presented provide compelling evidence that ferroptosis is closely associated with the therapeutic challenges of nervous system diseases.Targeted modulation of NRF2 to regulate ferroptosis holds substantial potential for effectively treating these diseases.Future NRF2-related research should not only focus on discovering new drugs but also on designing rational drug delivery systems.In particular,nanocarriers offer substantial potential for facilitating the clinical translation of NRF2 research and addressing existing issues related to NRF2-related drugs.

Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis

Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion.Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis.In this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition.Methods Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also conducted.Cell growth was assessed using the Cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow cytometry.Moreover,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets.Results Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell lines.RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152.Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors.We suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells.Conclusion Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

Cervical myeloid sarcoma as an initial clinical manifestation: Four case reports

BACKGROUND Cervical myeloid sarcoma(MS)is a rare hematological malignancy characterized by the formation of extramedullary soft tissue masses in the cervical region.Due to its uncommon presentation in the female reproductive system,cervical MS poses significant diagnostic and therapeutic challenges.Consequently,there is a pressing need for more research and clinical experience to better understand,diagnose,and manage this condition effectively.CASE SUMMARY This report details four cases,the diagnostic process,treatment strategy,and outcomes,discussing cervical MS as an initial clinical manifestation.The disease exhibits varied clinical presentations,such as irregular vaginal bleeding and pa-lpation of cervical masses.The treatment approaches discussed include neoad-juvant chemotherapy,surgery,and postoperative chemotherapy,though mana-ging the disease remains challenging.The report also features a comprehensive literature review that underscores the importance of immunohistochemistry for accurate diagnosis,identifying key markers,including myeloperoxidase,cluster of differentiation(CD)68,and CD43,stressing the need for further research to improve treatment strategies and prognosis.CONCLUSION Immunohistochemical diagnosis and tailored therapeutic strategies are essential.Further research is crucial in improving outcomes and developing effective treatment protocols.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Network pharmacology to decipher the mechanism of Danggui Longhui Wan against chronic myeloid leukemia

Chronic myeloid leukemia(CML)is a hematopoietic myeloproliferative disorder.The Chinese prescription Danggui Longhui Wan(DGLHW)has been utilized in CML treatment,but its underlying mechanisms remain unclear.In this study,we gathered 794 constituents,1249 drug targets,1654 disease genes and 129 intersection genes.GO and KEGG were used to analyze the function of these genes.Compatibility of prescription study showed that monarch drug,minister drug,assistant and guide drug played a synergistic role in the treatment of CML.In addition,we obtained 20 hub genes and 12 key components.Molecular docking indicated that the main compounds and core proteins had good binding ability.The results of this study also showed that DGLHW might play a role in the treatment of CML by affecting MAPK,PI3K/AKT,FoxO and p53 signaling pathways.

Clinical Effects of Venetoclax in the Treatment of Acute Myeloid Leukemia in the Elderly

Objective: To investigate the clinical efficacy of venetoclax in the treatment of elderly acute myeloid leukemia (AML). Methods: 50 cases of elderly AML patients receiving venetoclax for treatment in the hospital from January 2022 to January 2024 were selected, including 38 cases of patients whose primary treatment was not suitable for intensive chemotherapy and 12 cases of relapsed/refractory AML patients, to observe the therapeutic efficacy and safety of venetoclax. Results: Among the 38 patients whose primary treatment was not suitable for intensive chemotherapy, 5 cases were treated with venetoclax monotherapy, 33 cases were treated with venetoclax + azacitidine, and 25 patients (65.79%) achieved complete remission (CR) with incomplete hematologic recovery (CRi) after 28 days of treatment;10 patients with relapsed/refractory AML were treated with venetoclax + azacitidine, and 2 patients were treated with venetoclax + azacitidine + chemotherapy, and 2 patients achieved optimal therapeutic response after 28 days of treatment and CR/CRi was achieved in 7 patients (58.33%). There were 47 (94.0%) patients with grade 3 or higher granulocytopenia, 46 (92.0%) patients with hemoglobin reduction, and 43 (86.0%) patients with thrombocytopenia, developed after 28 days of treatment. 11 patients developed infections after treatment and there was one case of tumor lysis syndrome. Conclusion: The response rate of venetoclax monotherapy and combination in elderly AML induction therapy is high, and the overall tolerability of elderly patients is good, so it can be popularized and applied.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

Identification of key genes responsible for cytokine-induced erythroid and myeloid differentiation and switching of hematopoietic stem cells by RAGE

We utilized a unique culture system to analyze the expression patterns of gene, protein, and cell surface antigen, and the biological process of the related genes in erythroid and myeloid differentiation and switching of hematopoietic stem cells （HSCs） in response to cytokine alterations. Gene-specific fragments （266） identified from five populations of cytokine-stimulated HSCs were categorized into three groups： （1） expressed specifically in a single cell population; （2） expressed in two cell populations, and （3） expressed in three or more populations. Of 145 defined cDNAs, three （2%） were novel genes. Protein two-dimensional gel electrophoresis and flow cytometry analyses showed overlapped and distinguished protein expression profiles in the cell populations studied. Biological process mapping of mRNAs expressed in erythroid and myeloid lineages indicated that mRNAs shared by both lineages attended ＇core processes,＇ whereas genes specifically expressed in either lineage alone were related to specific processes or cellular maturation. Data from this study support the hypothesis that committed HSCs （El4 or G14） cells can still be redirected to develop into myeloid or erythroid cells when erythropoietin （EPO） is replaced with granulocyte-colony stimulating factor （G-CSF） under erythroid-cultured condition or G-CSF with EPO in myeloid-cultured environment, respectively. Our results suggest that genes or proteins co-expressed in erythroid and myeloid lineages may be essential for the lineage maintenance and switching in hematopoiesis.

Emerging trends and hotspots of Nuclear factor erythroid 2-related factor 2 in nervous system diseases

BACKGROUND The Nuclear factor erythroid 2-related factor 2(NRF2)transcription factor has attracted much attention in the context of neurological diseases.However,none of the studies have systematically clarified this field's research hotspots and evolution rules.AIM To investigate the research hotspots,evolution patterns,and future research trends in this field in recent years.METHODS We conducted a comprehensive literature search in the Web of Science Core Collection database using the following methods:(((((TS=(NFE2 L2))OR TS=(Nfe2 L2 protein,mouse))OR TS=(NF-E2-Related Factor 2))OR TS=(NRF2))OR TS=(NFE2L2))OR TS=(Nuclear factor erythroid2-related factor 2)AND(((((((TS=(neurological diseases))OR TS=(neurological disorder))OR TS=(brain disorder))OR TS=(brain injury))OR TS=(central nervous system disease))OR TS=(CNS disease))OR TS=(central nervous system disorder))OR TS=(CNS disorder)AND Language=English from 2010 to 2022.There are just two forms of literature available:Articles and reviews.Data were processed with the software Cite-Space(version 6.1.R6).RESULTS We analyzed 1884 articles from 200 schools in 72 countries/regions.Since 2015,the number of publications in this field has increased rapidly.China has the largest number of publications,but the articles published in the United States have better centrality and H-index.Among the top ten authors with the most published papers,five of them are from China,and the author with the most published papers is Wang Handong.The institution with the most articles was Nanjing University.To their credit,three of the top 10 most cited articles were written by Chinese scholars.The keyword co-occurrence map showed that"oxidative stress","NRF2","activation","expression"and"brain"were the five most frequently used keywords.CONCLUSION Research on the role of NRF2 in neurological diseases continues unabated.Researchers in developed countries published more influential papers,while Chinese scholars provided the largest number of articles.There have been numerous studies on the mechanism of NRF2 transcription factor in neurological diseases.NRF2 is also emerging as a potentially effective target for the treatment of neurological diseases.However,despite decades of research,our knowledge of NRF2 transcription factor in nervous system diseases is still limited.Further studies are needed in the future.

The Applications of Mitoxantrone and Its Liposome in Adult Acute Myeloid Leukemia

Acute myeloid leukemia (AML), a rapidly progressing hematopoietic malignancy, can only be cured hopefully by hematopoietic stem cells transplantation (HSCT). Before HSCT, we usually exert effects by attempting certain regimens to induce these tumor cells to death. Administered in AML patients, the classic “3 + 7” intensive induction regimen including anthracyclines and cytarabine is recommended by guidelines worldwide. However, conventional regimens consist of anthracyclines, a category of drug limited by cumulative, dose-related, progressive myocardial damage and congestive heart failure occurs when its total doses break through the cut-off. Based on this background, mitoxantrone (MIT), an anthraquinone, was developed to a new form to reduce cardiotoxicity. Meanwhile, the nanomedicine, mitoxantrone liposome (Lipo-MIT), was characterized by improved bioavailability and limited toxicity. This drug has great therapeutic potential, but different side effects. We conclude the overall history and development of MIT and Lipo-MIT, which show controversial efficacy of MIT compared to doxorubicin and therapeutic potential of Lipo-MIT. This article reviewed the application of MIT and liposome forms in adult AML patients. .

Myeloid sarcoma as the only manifestation in a rare mixed lineage leukemia-fusion-driven acute myeloid leukemia:A case report

BACKGROUND The mixed lineage leukemia(MLL)-eleven-nineteen lysine-rich leukemia(ELL)fusion gene is a rare occurrence among the various MLL fusion genes.We present the first case in which myeloid sarcoma(MS)was the only manifestation of adult MLL-ELL-positive acute myeloid leukemia(AML).CASE SUMMARY We report a case of a 33-year-old male patient who was admitted in June 2022 with a right occipital area mass measuring approximately 7 cm×8 cm.Blood work was normal.The patient underwent right occipital giant subscalp mass excision and incisional flap grafting.Immunohistochemistry was positive for myeloperoxidase,CD43 and CD45 and negative for CD3,CD20,CD34,and CD56.The bone marrow aspirate showed hypercellularity with 20%myeloblasts.Flow cytometry showed that myeloblasts accounted for 27.21%of the nucleated cells,which expressed CD33,CD38,and CD117.The karyotype was 46,XY,t(11,19)(q23;p13.1),-12,+mar/46,XY.Next-generation sequencing showed a fusion of MLL exon 7 to exon 2 of ELL.A diagnosis of MLL-ELL-positive AML(M2 subtype)with subcutaneous MS was made.CONCLUSION MLL-ELL-positive AML with MS is a rare clinical entity.Additional research is needed to elucidate the molecular mechanisms of the pathogenesis of MS.

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.

TNFSF15 facilitates the differentiation of CD11b^(+) myeloid cells into vascular pericytes in tumors

Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell dissemination.We previously demonstrated that tumor necrosis factor superfamily 15(TNFSF15)is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis.The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b^(+) cells and further into pericytes.Methods:A model of Lewis lung cancer was established in mice with red fluorescent bone marrow.After TNFSF15 treatment,CD11b^(+) myeloid cells and vascular pericytes in the tumors,and the co-localization of pericytes and vascular endothelial cells,were assessed.Additionally,CD11b^(+) cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.Results:We observed elevated percentages of bone marrow-derived CD11b^(+)myeloid cells and vascular pericytes in TNFSF15-treated tumors,and the latter cells co-localized with vascular endothelial cells.TNFSF15 protected against CD11b^(+)cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.Conclusions:TNFSF15 facilitates the production of CD11b^(+) cells in the bone marrow and promotes the differentiation of these cells into pericytes,which may stabilize the tumor neovasculature.

A model based on eight iron metabolism-related genes accurately predicts acute myeloid leukemia prognosis

Purpose:Iron metabolism maintains the balance between iron absorption and excretion.Abnormal iron metabolism can cause numerous diseases,including tumor.This study determined the iron metabolism-related genes(IMRGs)signature that can predict the prognosis of acute myeloid leukemia(AML).The roles of these genes in the immune microenvironment were also explored.Methods:A total of 514 IMRGs were downloaded from the Molecular Characteristics Database(MSigDB).IMRGs related to AML prognosis were identified using Cox regression and LASSO analyses and were used to construct the risk score model.AML patients were stratified into high-risk groups(cluster 1)and low-risk groups(cluster 2)based on the mean value of the risk score.The accuracy and prognosis prediction potential of the risk-score model was evaluated using Kaplan-Meier and receiver operating characteristics analysis.The stromal score,immune scores,and immune cells infiltrated in AML samples were estimated using CIBERSORT,MCPcountre,and Xcell algorithms.The role of immune checkpoint genes in the AML microenvironment and the prognostic value of the IMRGs were also evaluated.Results:An AML prognosis prediction model was established based on the eight most critical IMRGs.Further analyses revealed that the model could accurately predict AML prognosis.The expression of IMRGs correlated with the infiltration of several immune cells and could influence response to certain chemotherapy drugs and immunotherapy.Conclusion:A model based on IMRGs can accurately predict the overall survival and disease-free survival of AML patients.

Acute pancreatitis as initial presentation of acute myeloid leukemia-M2 subtype:A case report

BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicated as the cause of AP.Pancreatitis caused by a rare predisposing factor is often misdiagnosed as idiopathic pancreatitis or pancreatitis of other common causes.Severe AP(SAP)progresses rapidly with a high fatality rate.Therefore,it is important to identify the predisposing factors in the early stage of SAP,evaluate the condition,determine prognosis,formulate treatment plans,and prevent a recurrence.Here,we describe a case of SAP due to AML.CASE SUMMARY A 61-year-old man presented to the hospital with fever and persistent abdominal pain.Blood analysis presented significantly elevated serum amylase and severe thrombocytopenia.Computed tomography examination of the abdomen revealed peripancreatic inflammatory effusion.The patient had no common etiologies and risk factors for AP,but the concurrent severe thrombocytopenia could not be explained by pancreatitis.Finally,the bone marrow aspirate and biopsy inspection revealed the underlying reason for pancreatitis,AML(M2 type based on the French-American-British classifications system).CONCLUSION Direct infiltration of the pancrease by acute leukemia,particularly AML cells,is an infrequent cause of AP.Therefore,although AP is a rare extramedullary infilt-ration characteristic for AML patients,it should be considered when determining the etiology of AP.