FHL1 as a prognostic biomarker and therapeutic target in acute myeloid leukemia

FHL1 as a prognostic biomarker and therapeutic target in acute myeloid leukemia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article FHL1 as a prognostic biomarker and therapeutic target in acute myeloid leukemia Bo Luo, Wei Li, Jialing Li, Guanfei Chen, Jingyuan Zeng, Nan Hu, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2854959/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Acute myeloid leukemia (AML) has a poor prognosis and high heterogeneity. Most leukemias are caused by environmental factors interacting with the cell’s genetic material, but treatment is still dominated by cell cycle drugs. Therefore, there is an urgent need to find reliable biomarkers. Based on the Gene Expression Omnibus database, Kaplan–Meier survival analysis and univariate Cox regression analysis were used to select the genes that had the most significant influence on the prognosis of patients with AML. Quantitative real-time PCR and Western blot were used to detect the effect of small interfering RNA transfection and lentiviral interference on knockout and overexpression of the gene, respectively, and to verify the difference in the FHL1 gene in the HL60 cell line and neutrophils. Cell Counting Kit-8 and flow cytometry were used to detect the effect of high or low expression of FHL1 on cell viability and apoptosis under the influence of cytarabine and daunorubicin. FHL1 was found to be the most prognostic independent biomarker by GSE12417 screening and GSE37642 validation. FHL1 is highly expressed in AML, and knockdown of FHL1 can increase the sensitivity of AML cells to cytarabine and daunorubicin. FHL1 may play a role as a potential molecular marker and therapeutic target for predicting poor prognosis of AML and for direct treatment (adjuvant radiotherapy or chemotherapy). Biological sciences/Cancer Biological sciences/Cancer/Haematological cancer Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations No competing interests reported. Supplementary Files figureS1.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2854959","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":198475054,"identity":"85fffd07-e081-4d43-992e-fefe996abac2","order_by":0,"name":"Bo Luo","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Luo","suffix":""},{"id":198475056,"identity":"1e6ea8c8-15b4-4ea1-8ac8-b5624061b758","order_by":1,"name":"Wei Li","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Li","suffix":""},{"id":198475058,"identity":"e2d03261-337d-41ba-a694-79da6c42d200","order_by":2,"name":"Jialing Li","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jialing","middleName":"","lastName":"Li","suffix":""},{"id":198475059,"identity":"8173c41b-698e-4ec3-b6ec-3bc63a2acd07","order_by":3,"name":"Guanfei Chen","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guanfei","middleName":"","lastName":"Chen","suffix":""},{"id":198475060,"identity":"3af37f3f-fb3c-423a-a641-159bb66620cf","order_by":4,"name":"Jingyuan Zeng","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jingyuan","middleName":"","lastName":"Zeng","suffix":""},{"id":198475061,"identity":"313b4ca1-d9c0-4d41-b8ba-768aa66e76ba","order_by":5,"name":"Nan Hu","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nan","middleName":"","lastName":"Hu","suffix":""},{"id":198475062,"identity":"31aa59a5-4f8b-4aa0-8ec6-901ef4b0ce97","order_by":6,"name":"Lulu Li","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lulu","middleName":"","lastName":"Li","suffix":""},{"id":198475063,"identity":"18417e47-1221-4236-923f-a70533e901d6","order_by":7,"name":"Zhongming He","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhongming","middleName":"","lastName":"He","suffix":""},{"id":198475065,"identity":"0b47ecdd-9176-42cb-88c8-45f027fb7ab7","order_by":8,"name":"Shuang He","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shuang","middleName":"","lastName":"He","suffix":""},{"id":198475066,"identity":"4f762977-324b-41ca-a4a0-da717bec2af5","order_by":9,"name":"Qulian Guo","email":"","orcid":"","institution":"The Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qulian","middleName":"","lastName":"Guo","suffix":""},{"id":198475068,"identity":"280121ed-7bc9-4745-88c4-9eb818d3af67","order_by":10,"name":"Xiaoli Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYDACdgY2EMXDxszY+CChwoYILcwQLTJ87MzNBg/OpBGvxUaOn71N8mHbIcI6DA6zP3vwcUctyGFtFQlsBxj427sT8GqRbGZIN5x55jhYy40EnjsMEmfObsCrhZ+Z4Zg0b9sxqBaJZwwGErn4tYBUSv+FailIMDhMWAs/MzObNGNbDVgLQ0ICEVokm9nYJHvbDoC0NEskHEjjIegXg+PtzyR+ttXZy/cff/jx5z9gYLf34tcCBYfhLB5ilINAHbEKR8EoGAWjYCQCAPZEQJqOn+/rAAAAAElFTkSuQmCC","orcid":"","institution":"Southwest Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xiaoli","middleName":"","lastName":"Zheng","suffix":""}],"badges":[],"createdAt":"2023-04-24 13:29:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2854959/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2854959/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":36928651,"identity":"7e7c4c42-043b-4f29-9735-c611eea09fec","added_by":"auto","created_at":"2023-05-12 03:22:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":958398,"visible":true,"origin":"","legend":"\u003cp\u003eIdentification of independent prognostic factors for acute myeloid leukemia (AML). Based on the influence of FHL1 expression on the overall survival of patients with AML in the Gene Expression Omnibus dataset, GSE12417 is the training set and GSE37642 is the verification set (A, B). The association of FHL1 expression with clinicopathological features, including differences in the distribution of FBA typing and age (C, D), and univariate and multivariate Cox analyses for these factors (E).\u0026nbsp;\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2854959/v1/ed536cfd99f9d8e2b7f46be5.png"},{"id":36927492,"identity":"16133ab0-004d-4e29-b083-92290680007e","added_by":"auto","created_at":"2023-05-12 03:18:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1219306,"visible":true,"origin":"","legend":"\u003cp\u003eDifference analysis and pathway analysis of FHL1 high- and low-expression groups based on the GSE12417 dataset. Volcano maps (A) and heat maps (B) were used to visualize differentially expressed genes in the high- and low-FHL1-expression groups, with red representing high or upregulated genes and green representing low or downregulated genes. Pathway analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes of differentially expressed genes (C, D). Correlation analysis between differential genes (E).\u0026nbsp;\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-2854959/v1/4b8783d0b160ea4f8c96da58.png"},{"id":36925606,"identity":"4586ef60-cbf7-4e09-8210-4170987dee77","added_by":"auto","created_at":"2023-05-12 03:11:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":878574,"visible":true,"origin":"","legend":"\u003cp\u003eA: FHL1 gene differential expression was analyzed in 337 whole blood RNA sequencing data from Genotype-Tissue Expression and 379 acute myeloid leukemia samples . B: Silencing and overexpression of FHL1 gene siRNA in HL60 cells, expression of FHL1 protein in normal human peripheral blood neutrophils (PMN), HL60 cell control (Con), and ß-Tubulin as an internal reference protein. C: qRT-PCR detected the mRNA expression level of FHL1. D: Western Blot grayscale value quantification. *P\u0026lt;0.05;**P\u0026lt;0.01;***P\u0026lt;0.001, the difference was statistically significant.\u0026nbsp;\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-2854959/v1/24718e00062ec09d5ed3e415.png"},{"id":36928652,"identity":"e3599548-ece1-434a-b713-77629c744fa0","added_by":"auto","created_at":"2023-05-12 03:22:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1124535,"visible":true,"origin":"","legend":"\u003cp\u003eA : Proliferation effect of FHL1 on HL60 cell line under drug treatment. B : Cell Counting Kit-8 was used to detect the effect of Ara-C and DNR different concentrations on cell proliferation under the silenced FHL1. C : Cell Counting Kit-8 was used to detect the effect of Ara-C and DNR different concentrations on cell proliferation under the overexpressed FHL1.\u0026nbsp;\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-2854959/v1/5918be7d51189ce53a17e8ca.png"},{"id":36929407,"identity":"a9e745c9-28a0-46b4-a512-cfe15fba22f7","added_by":"auto","created_at":"2023-05-12 03:25:45","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2045376,"visible":true,"origin":"","legend":"\u003cp\u003eStudy of the effect of FHL1 on apoptosis of HL60 cell lines under drug treatment. The apoptosis of cells treated with different concentrations of Ara-C (A) and DNR (B) was detected under the silenced and overexpressed FHL1.\u0026nbsp;\u003c/p\u003e","description":"","filename":"figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-2854959/v1/aae4acec34a79cb4f09a0531.png"},{"id":36928775,"identity":"f7227c41-ab78-4073-b334-5001bee0d4d5","added_by":"auto","created_at":"2023-05-12 03:22:55","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":492786,"visible":true,"origin":"","legend":"\u003cp\u003eGene set enrichment analysis based on the FHL1 gene in the GSE12417 dataset showed a significant enrichment pathway.\u0026nbsp;\u003c/p\u003e","description":"","filename":"figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-2854959/v1/8aed7c2ae28e4bb0e79de26c.png"},{"id":37635490,"identity":"89b7549b-4cf3-45be-959f-7cd2e10f39e8","added_by":"auto","created_at":"2023-05-30 06:59:30","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":773873,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2854959/v1_covered_0a6e94e3-15d2-47d5-aaf4-a4178aea7dc1.pdf"},{"id":36930750,"identity":"0d9d1ffa-f773-49e0-b915-ae121ba712a8","added_by":"auto","created_at":"2023-05-12 03:32:11","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":215369,"visible":true,"origin":"","legend":"","description":"","filename":"figureS1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2854959/v1/6c43ad215a27f94b6b3f8f7a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"FHL1 as a prognostic biomarker and therapeutic target in acute myeloid leukemia","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-2854959/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2854959/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Acute myeloid leukemia (AML) has a poor prognosis and high heterogeneity. Most leukemias are caused by environmental factors interacting with the cell’s genetic material, but treatment is still dominated by cell cycle drugs. Therefore, there is an urgent need to find reliable biomarkers. Based on the Gene Expression Omnibus database, Kaplan–Meier survival analysis and univariate Cox regression analysis were used to select the genes that had the most significant influence on the prognosis of patients with AML. Quantitative real-time PCR and Western blot were used to detect the effect of small interfering RNA transfection and lentiviral interference on knockout and overexpression of the gene, respectively, and to verify the difference in the FHL1 gene in the HL60 cell line and neutrophils. Cell Counting Kit-8 and flow cytometry were used to detect the effect of high or low expression of FHL1 on cell viability and apoptosis under the influence of cytarabine and daunorubicin. FHL1 was found to be the most prognostic independent biomarker by GSE12417 screening and GSE37642 validation. FHL1 is highly expressed in AML, and knockdown of FHL1 can increase the sensitivity of AML cells to cytarabine and daunorubicin. FHL1 may play a role as a potential molecular marker and therapeutic target for predicting poor prognosis of AML and for direct treatment (adjuvant radiotherapy or chemotherapy).","manuscriptTitle":"FHL1 as a prognostic biomarker and therapeutic target in acute myeloid leukemia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-05-11 21:53:45","doi":"10.21203/rs.3.rs-2854959/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"65e32fbd-2c23-4093-82bc-d1d55d745fb9","owner":[],"postedDate":"May 11th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":21272744,"name":"Biological sciences/Cancer"},{"id":21272745,"name":"Biological sciences/Cancer/Haematological cancer"}],"tags":[],"updatedAt":"2023-05-30T06:59:14+00:00","versionOfRecord":[],"versionCreatedAt":"2023-05-11 21:53:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2854959","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2854959","identity":"rs-2854959","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}