{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:14:00Z","timestamp":1753892040298,"version":"3.41.2"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Stromal-cell-derived factor 1 (SDF-1) plays a crucial role in hematopoiesis and has been implicated in acute myeloid leukemia (AML) pathogenesis. Understanding its relationship with chemotherapy outcomes could lead to improved therapeutic approaches for elderly AML patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study retrospectively analyzed the medical records of elderly AML patients (n = 187) and compared serum SDF-1\u03b1 levels with age-matched controls (n = 120). Patients received CAG (cytarabine, aclarubicin, and G\u2010CSF)-based chemotherapy, and serum SDF-1\u03b1 levels were assessed using ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum SDF-1\u03b1 levels were significantly elevated in elderly AML patients compared to controls (p &amp;lt; 0.001). Receiver operating characteristic (ROC) analysis confirmed its diagnostic relevance, revealing the area under the ROC curve (AUC) of 0.76. Factors such as age, French-American-British (FAB) classification, Eastern Cooperative Oncology Group (ECOG) performance status, primary AML status, white blood cell count, and bone marrow blast cell ratio, were confirmed to be prognostically relevant. Serum SDF-1\u03b1 levels were elevated in patients who did not achieve complete remission (NCR) compared to those in complete remission (CR). ROC analysis further highlighted the predictive capability of serum SDF-1\u03b1 for chemotherapy responsiveness. Independent predictors of treatment failure included age, FAB classification, ECOG status, and serum SDF-1\u03b1 levels. Following chemotherapy, serum SDF-1\u03b1 levels decreased in patients in CR but remained unchanged in those in NCR. Higher baseline levels of SDF-1\u03b1 were associated with shorter overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Elevated serum SDF-1\u03b1 levels in elderly AML patients are associated with poor chemotherapy response and shorter survival. Baseline serum SDF-1\u03b1 levels could serve as a prognostic marker for CAG-based treatment outcomes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2024.1521179","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T06:10:44Z","timestamp":1736748644000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum stromal cell-derived factor 1\u03b1 as a prognostic indicator in elderly patients with acute myeloid leukemia receiving CAG-based chemotherapy"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhenzhen","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianfeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"120","DOI":"10.3390\/cancers12010120","article-title":"Therapeutic choice in older patients with acute myeloid leukemia: A matter of fitness","volume":"12","author":"Palmieri","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1159\/000531628","article-title":"Acute myeloid leukemia treatment in the elderly: A comprehensive review of the present and future","volume":"146","author":"Choi","year":"2023","journal-title":"Acta Haematol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-021-01474-9","article-title":"Exciting times ahead for older patients with acute myeloid leukemia: azacitidine and venetoclax followed by allogeneic hematopoietic cell transplantation","volume":"57","author":"Bazarbachi","year":"2022","journal-title":"Bone Marrow Transplant"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.191536","article-title":"Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged 75 years or older","volume":"103","author":"Prassek","year":"2018","journal-title":"Haematologica"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00590","article-title":"The role of SDF-1\/CXCR4\/CXCR7 in neuronal regeneration after cerebral ischemia","volume":"11","author":"Cheng","year":"2017","journal-title":"Front Neurosci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/0300060519876138","article-title":"Stromal cell-derived factor-1\/CXC chemokine receptor 4 axis in injury repair and renal transplantation","volume":"47","author":"Sun","year":"2019","journal-title":"J Int Med Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.10.010","article-title":"The role of stromal cell-derived factor 1 on cartilage development and disease","volume":"29","author":"Li","year":"2021","journal-title":"Osteoarthr Cartil"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6396","article-title":"Role of C-X-C chemokine ligand 12\/C-X-C chemokine receptor 4 in the progression of hepatocellular carcinoma","volume":"14","author":"Jeng","year":"2017","journal-title":"Oncol Lett"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.2017.25.issue-4","article-title":"CXCR4 antagonist delivery on decellularized skin scaffold facilitates impaired wound healing in diabetic mice by increasing expression of SDF-1 and enhancing migration of CXCR4-positive cells","volume":"25","author":"Liu","year":"2017","journal-title":"Wound Repair Regener"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2174\/0929867324666170830111531","article-title":"Targeting CXCL12\/CXCR4 axis in tumor immunotherapy","volume":"26","author":"Zhou","year":"2019","journal-title":"Curr Med Chem"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgn045","article-title":"Bone-derived SDF-1 stimulates IL-6 release via CXCR4, ERK and NF-kappaB pathways and promotes osteoclastogenesis in human oral cancer cells","volume":"29","author":"Tang","year":"2008","journal-title":"Carcinogenesis"},{"key":"B12","doi-asserted-by":"publisher","first-page":"77S","DOI":"10.2967\/jnumed.116.186874","article-title":"CXCR4 ligands: the next big hit","volume":"58","author":"Walenkamp","year":"2017","journal-title":"J Nucl Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s00223-017-0245-8","article-title":"Association of plasma SDF-1 with bone mineral density, body composition, and hip fractures in older adults: the cardiovascular health study","volume":"100","author":"Carbone","year":"2017","journal-title":"Calcif Tissue Int"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2006","article-title":"Functional CXCR4-expressing microparticles and SDF-1 correlate with circulating acute myelogenous leukemia cells","volume":"66","author":"Kalinkovich","year":"2006","journal-title":"Cancer Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.31557\/APJCP.2021.22.4.1035","article-title":"Association of SDF-1 gene polymorphism with increased risk of acute myeloid leukemia patients","volume":"22","author":"Aladle","year":"2021","journal-title":"Asian Pac J Cancer Prev"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.v8.15","article-title":"Prognostic significance of CXCR4 expression in acute myeloid leukemia","volume":"8","author":"Du","year":"2019","journal-title":"Cancer Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e13076","DOI":"10.1111\/cpr.13076","article-title":"Role of CXCR4 in the progression and therapy of acute leukaemia","volume":"54","author":"Su","year":"2021","journal-title":"Cell Prolif"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2013.01.016","article-title":"Endogenous stromal cell-derived factor-1 (CXCL12) supports autonomous growth of acute myeloid leukemia cells","volume":"37","author":"Kim","year":"2013","journal-title":"Leuk Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3892\/etm.2020.9471","article-title":"Role of the stromal cell derived factor-1 in the biological functions of endothelial progenitor cells and its underlying mechanisms","volume":"21","author":"Cun","year":"2021","journal-title":"Exp Ther Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2016.3343","article-title":"Overexpression of SDF-1 activates the NF-kappaB pathway to induce epithelial to mesenchymal transition and cancer stem cell-like phenotypes of breast cancer cells","volume":"48","author":"Kong","year":"2016","journal-title":"Int J Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-158311","article-title":"Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML","volume":"113","author":"Zeng","year":"2009","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","first-page":"563","DOI":"10.3390\/ijms24010563","article-title":"Bone marrow microenvironment as a source of new drug targets for the treatment of acute myeloid leukaemia","volume":"24","author":"Skelding","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1097\/FJC.0b013e3181d7a384","article-title":"SDF-1\/CXCR4-mediated migration of transplanted bone marrow stromal cells toward areas of heart myocardial infarction through activation of PI3K\/Akt","volume":"55","author":"Yu","year":"2010","journal-title":"J Cardiovasc Pharmacol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/07357907.2017.1422512","article-title":"Knockdown of CXCR4 inhibits CXCL12-induced angiogenesis in HUVECs through downregulation of the MAPK\/ERK and PI3K\/AKT and the Wnt\/\u03b2-catenin pathways","volume":"36","author":"Song","year":"2018","journal-title":"Cancer Invest"},{"key":"B25","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1159\/000497430","article-title":"CXC chemokine receptor 4 in diffuse large B cell lymphoma: achievements and challenges","volume":"142","author":"Du","year":"2019","journal-title":"Acta Haematol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4508108","DOI":"10.1155\/2020\/4508108","article-title":"miR-142-5p as a CXCR4-targeted microRNA attenuates SDF-1-induced chondrocyte apoptosis and cartilage degradation via inactivating MAPK signaling pathway","volume":"2020","author":"Xiang","year":"2020","journal-title":"Biochem Res Int"},{"key":"B27","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1002\/ajh.26079","article-title":"Determination of fitness and therapeutic options in older patients with acute myeloid leukemia","volume":"96","author":"Cortes","year":"2021","journal-title":"Am J Hematol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01745-4","article-title":"Effect of ECOG performance status on outcomes in patients with acute myeloid leukemia and other high-grade myeloid neoplasms","volume":"37","author":"Paras","year":"2023","journal-title":"Leukemia"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24640","article-title":"Impact of FAB classification on predicting outcome in acute myeloid leukemia, not otherwise specified, patients undergoing allogeneic stem cell transplantation in CR1: An analysis of 1690 patients from the acute leukemia working party of EBMT","volume":"92","author":"Canaani","year":"2017","journal-title":"Am J Hematol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/bcr1022","article-title":"Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer","volume":"7","author":"Kang","year":"2005","journal-title":"Breast Cancer Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2021.05.004","article-title":"SDF-1alpha predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma receiving definitive concurrent chemoradiotherapy","volume":"45","author":"Chen","year":"2022","journal-title":"BioMed J"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-024844","article-title":"CXCR4 is a prognostic marker in acute myelogenous leukemia","volume":"109","author":"Spoo","year":"2007","journal-title":"Blood"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1521179\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T06:10:47Z","timestamp":1736748647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1521179\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,13]]},"references-count":32,"alternative-id":["10.3389\/fonc.2024.1521179"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2024.1521179","relation":{},"ISSN":["2234-943X"],"issn-type":[{"type":"electronic","value":"2234-943X"}],"subject":[],"published":{"date-parts":[[2025,1,13]]},"article-number":"1521179"}}