{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T01:50:42Z","timestamp":1785289842708,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adult acute lymphoblastic leukemia (ALL) is a highly heterogeneous hematologic malignancy where treatment response and relapse risk do not exclusively rely on the identification of genetic lesions but also on dynamic biological states sustained by specific transcriptional and epigenetic programs. Although the integrated application of multi-omics approaches has significantly expanded our knowledge of oncogenic dependencies, cellular plasticity, and mechanisms of therapeutic resistance, its systematic translation into the clinical practice of adult ALL is yet to become a reality. The aim of this review is to provide a critical and focused synthesis on how the integration of genomics, transcriptomics, and epigenetics enables the interpretation of disease biological behaviors and may guide personalized therapeutic strategies while simultaneously addressing the major limitations that hinder clinical implementation. Genomics allows for the identification of driver events and pharmacologically actionable vulnerabilities, whereas transcriptomics, including single-cell analyses, reveals functional states associated with clonal persistence, glucocorticoid resistance, and therapeutic adaptation, even in the absence of new mutations. In parallel, epigenetic signatures emerge as key elements in stabilizing oncogenic programs and resistant phenotypes, contributing to the biological plasticity of leukemic cells and representing potentially reversible therapeutic targets. Taken together, multi-omics signatures provide an integrated functional readout of adult ALL and support a dynamic precision-medicine model. However, adaptive therapeutic decisions aimed at relapse prevention require the full integration of these approaches through standardized strategies, longitudinal studies, and a sustainable implementation of molecular profiling and minimal residual disease monitoring.<\/jats:p>","DOI":"10.3390\/ijms27073335","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T13:14:19Z","timestamp":1775567659000},"page":"3335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi-Omics Applications in Adult Acute Lymphoblastic Leukemia: From Biological Mechanisms to Precision Therapies"],"prefix":"10.3390","volume":"27","author":[{"given":"Claudia","family":"Simio","sequence":"first","affiliation":[{"name":"Department of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-4406","authenticated-orcid":false,"given":"Matteo","family":"Molica","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9280-2023","authenticated-orcid":false,"given":"Laura","family":"De Fazio","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7258-475X","authenticated-orcid":false,"given":"Marco","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sucre, O., Pamulapati, S., Muzammil, Z., and Bitran, J. (2025). Advances in Therapy of Adult Patients with Acute Lymphoblastic Leukemia. Cells, 14.","DOI":"10.3390\/cells14050371"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/cas.15583","article-title":"Oncogenic lesions and molecular subtypes in adults with B-cell acute lymphoblastic leukemia","volume":"114","author":"Yasuda","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/s41375-025-02599-2","article-title":"T-cell acute lymphoblastic leukaemia: Subtype prevalence, clinical outcome, and emerging targeted treatments","volume":"39","author":"Buckley","year":"2025","journal-title":"Leukemia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2174\/1566523220999201111194554","article-title":"Epigenetic modifications in acute lymphoblastic leukemia: From cellular mechanisms to therapeutics","volume":"21","author":"Fathi","year":"2021","journal-title":"Curr. Gene Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11899-025-00764-z","article-title":"Transforming the Treatment of Acute Lymphoblastic Leukemia: The Role of Bispecific Antibodies, Antibody-Drug Conjugates, and CAR T-cell Therapy","volume":"20","author":"Najdi","year":"2025","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/BS9.0000000000000102","article-title":"Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia","volume":"4","author":"Zhu","year":"2022","journal-title":"Blood Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Iacobucci, I., Kimura, S., and Mullighan, C.G. (2021). Biologic and Therapeutic Implications of Genomic Alterations in Acute Lymphoblastic Leukemia. J. Clin. Med., 10.","DOI":"10.3390\/jcm10173792"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hernandez-Valladares, M. (2023). Multi-Omic Approaches to Classify, Predict, and Treat Acute Leukemias. Cancers, 15.","DOI":"10.3390\/cancers15041049"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.5045\/br.2020.S004","article-title":"Minimal residual disease in acute lymphoblastic leukemia: Technical aspects and implications for clinical interpretation","volume":"55","author":"Kim","year":"2020","journal-title":"Blood Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4006","DOI":"10.1182\/bloodadvances.2022007378","article-title":"High-sensitivity next-generation sequencing MRD assessment in ALL identifies patients at very low risk of relapse","volume":"6","author":"Short","year":"2022","journal-title":"Blood Adv."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shahzad, M., Amin, M.K., and Badar, T. (2025). Upfront Immunotherapy Approaches in the Management of Adults with Acute Lymphoblastic Leukemia. Cancers, 17.","DOI":"10.3390\/cancers17172746"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00428-022-03448-8","article-title":"International Consensus Classification of acute lymphoblastic leukemia\/lymphoma","volume":"482","author":"Duffield","year":"2022","journal-title":"Virchows Arch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000547135","article-title":"Genomic Subclassification and Risk Stratification of ALL","volume":"149","author":"Iacobucci","year":"2025","journal-title":"Acta Haematol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chuang, S., Chu, A., Hurtado, R., and Tirado, C.A. (2025). Integrative Insights into Philadelphia-like B-Cell Acute Lymphoblastic Leukemia: A Genetic and Molecular Landscape. Diagnostics, 15.","DOI":"10.3390\/diagnostics15030385"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1182\/blood.2023022920","article-title":"Classification and risk stratification in T-lineage acute lymphoblastic leukemia","volume":"145","author":"Mullighan","year":"2025","journal-title":"Blood"},{"key":"ref_16","first-page":"206","article-title":"Contribution of copy number to improve risk stratification of adult T-cell acute lymphoblastic leukemia patients enrolled in measurable residual disease-oriented trials","volume":"110","author":"Morgades","year":"2025","journal-title":"Haematologica"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Song, Y., Fang, Q., and Mi, Y. (2022). Prognostic significance of copy number variation in B-cell acute lymphoblastic leukemia. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.981036"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nrclinonc.2015.38","article-title":"Genomics in acute lymphoblastic leukaemia: Insights and treatment implications","volume":"12","author":"Roberts","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/s43018-020-00124-1","article-title":"Mutational and functional genetics mapping of chemotherapy resistance mechanisms in relapsed acute lymphoblastic leukemia","volume":"1","author":"Oshima","year":"2020","journal-title":"Nat. Cancer"},{"key":"ref_20","first-page":"3046","article-title":"Multiclonal complexity of pediatric acute lymphoblastic leukemia and the prognostic relevance of subclonal mutations","volume":"106","author":"Yu","year":"2021","journal-title":"Haematologica"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/leu.2017.303","article-title":"RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia","volume":"32","author":"Jerchel","year":"2018","journal-title":"Leukemia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/ejh.14164","article-title":"Transcriptome analysis of primary adult B-cell lineage acute lymphoblastic leukemia identifies pathogenic variants and gene fusions, and predicts subtypes for in depth molecular diagnosis","volume":"112","author":"Podgorica","year":"2024","journal-title":"Eur. J. Haematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2120787119","DOI":"10.1073\/pnas.2120787119","article-title":"Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases","volume":"119","author":"Dai","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1182\/blood.2024028019","article-title":"Enhancer heterogeneity in acute lymphoblastic leukemia drives differential gene expression in patients","volume":"146","author":"Smith","year":"2025","journal-title":"Blood"},{"key":"ref_25","first-page":"132","article-title":"Transcriptomics paving the way for improved diagnostics and precision medicine of acute leukemia","volume":"79","author":"Mitelman","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5620","DOI":"10.1038\/s41598-025-86148-y","article-title":"Integrating bulk RNA-seq and scRNA-seq data to explore diverse cell death patterns and develop a programmed cell death-related relapse prediction model in pediatric B-ALL","volume":"15","author":"Luo","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wu, X., and Zhang, J. (2026). Multi-Omics Approaches to Understanding Therapy Resistance in Acute Lymphoblastic Leukemia. Lymphatics, 4.","DOI":"10.3390\/lymphatics4010008"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6240","DOI":"10.1182\/bloodadvances.2023010380","article-title":"Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia","volume":"7","author":"Cao","year":"2023","journal-title":"Blood Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1182\/blood-2023-190180","article-title":"Single Cell Transcriptomic Analysis of B-Cell Acute Lymphoblastic Leukemia (B-ALL) Reveals Correlation between Leukemia Cell State, Genetic Alterations and Clinical Outcome","volume":"142","author":"Iacobucci","year":"2023","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1182\/blood.2022016954","article-title":"Single-cell analysis of acute lymphoblastic and lineage-ambiguous leukemia: Approaches and molecular insights","volume":"141","author":"Iacobucci","year":"2023","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.1158\/1078-0432.CCR-16-2880","article-title":"Stabilization of Notch1 by the Hsp90 Chaperone is Crucial for T-Cell Leukemogenesis","volume":"23","author":"Wang","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cabaud-Gibouin, V., Durand, M., Qu\u00e9r\u00e9, R., Girodon, F., Garrido, C., and Jego, G. (2023). Heat-Shock Proteins in Leukemia and Lymphoma: Multitargets for Innovative Therapeutic Approaches. Cancers, 15.","DOI":"10.3390\/cancers15030984"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.3892\/ijo.2015.3139","article-title":"FOXM1 is overexpressed in B-acute lymphoblastic leukemia (B-ALL) and its inhibition sensitizes B-ALL cells to chemotherapeutic drugs","volume":"47","author":"Consolaro","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6471","DOI":"10.1038\/ncomms7471","article-title":"Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia","volume":"6","author":"Buchner","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1038\/s43018-025-00987-2","article-title":"Multipotent lineage potential in B cell acute lymphoblastic leukemia is associated with distinct cellular origins and clinical features","volume":"6","author":"Iacobucci","year":"2025","journal-title":"Nat. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2174\/2589977512666200220122650","article-title":"Gene Expression and Resistance to Glucocorticoid-Induced Apoptosis in Acute Lymphoblastic Leukemia: A Brief Review and Update","volume":"12","author":"Lambrou","year":"2020","journal-title":"Curr. Drug Res. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s43018-020-0037-3","article-title":"Integrative genomic analyses reveal mechanisms of glucocorticoid resistance in acute lymphoblastic leukemia","volume":"1","author":"Autry","year":"2020","journal-title":"Nat. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Olivas-Aguirre, M., Torres-L\u00f3pez, L., Pottosin, I., and Dobrovinskaya, O. (2021). Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.617937"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/cncr.35051","article-title":"A surrogate molecular approach for the detection of Philadelphia chromosome\u2013like B-acute lymphoblastic leukemia","volume":"130","author":"Gupta","year":"2023","journal-title":"Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41408-020-0313-6","article-title":"NARASIMHA: Novel Assay based on Targeted RNA Sequencing to Identify ChiMeric Gene Fusions in Hematological Malignancies","volume":"10","author":"Patkar","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1080\/10428194.2021.1999439","article-title":"PHi-RACE: PGIMER in-house rapid & cost effective classifier for the detection of BCR-ABL1 -like acute lymphoblastic leukaemia in Indian patients","volume":"63","author":"Gupta","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/ijlh.14370","article-title":"Application of Gene Expression Microarray for the Classification of Ph-Like B-Cell Acute Lymphoblastic Leukemia","volume":"47","author":"Thangrua","year":"2025","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41416-023-02294-y","article-title":"Evaluation of adverse prognostic gene alterations & MRD positivity in BCR::ABL1-like B-lineage acute lymphoblastic leukaemia patients, in a resource-constrained setting","volume":"129","author":"Gupta","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1002\/cncr.34665","article-title":"Genomic and proteomic characterization of Philadelphia-like B-lineage acute lymphoblastic leukemia: A report of Indian patients","volume":"129","author":"Gupta","year":"2023","journal-title":"Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s40291-025-00775-9","article-title":"Bridging the Gap: Cost-Effective Strategies for Detecting Ph-Like B-Lineage ALL in Resource-Limited Settings","volume":"29","author":"Gupta","year":"2025","journal-title":"Mol. Diagn. Ther."},{"key":"ref_46","first-page":"e45929","article-title":"Expression of CXCL8 (IL-8) in the Pathogenesis of T-Cell Acute Lymphoblastic Leukemia Patients","volume":"15","author":"Pandey","year":"2023","journal-title":"Cureus"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Veselinova, Y., Esteller, M., and Ferrer, G. (2025). Age-Driven Genetic and Epigenetic Heterogeneity in B-ALL. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26188774"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e916","DOI":"10.1097\/HS9.0000000000000916","article-title":"Emerging Epigenetic and Posttranslational Mechanisms Controlling Resistance to Glucocorticoids in Acute Lymphoblastic Leukemia","volume":"7","author":"Borin","year":"2023","journal-title":"HemaSphere"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, G., Wang, Y., Ye, L., Peng, L., Shi, R., Guo, S., He, J., Yang, H., and Dai, Q. (2024). Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: A systematic review. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1324859"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1080\/15592294.2019.1699991","article-title":"DOT1L: A key target in normal chromatin remodelling and in mixed-lineage leukaemia treatment","volume":"15","author":"Sarno","year":"2019","journal-title":"Epigenetics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102191","DOI":"10.1016\/j.gde.2024.102191","article-title":"Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia","volume":"86","author":"Milne","year":"2024","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e64148","DOI":"10.7554\/eLife.64148","article-title":"HOXA9 promotes MYC-mediated leukemogenesis by maintaining gene expression for multiple anti-apoptotic pathways","volume":"10","author":"Miyamoto","year":"2021","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Porazzi, P., De Dominici, M., Salvino, J., and Calabretta, B. (2021). Targeting the CDK6 Dependence of Ph+ Acute Lymphoblastic Leukemia. Genes, 12.","DOI":"10.3390\/genes12091355"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Follini, E., Marchesini, M., and Roti, G. (2019). Strategies to Overcome Resistance Mechanisms in T-Cell Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123021"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Novo, C.A., Driesen, A., Van Trimpont, M., Theys, C., Logie, E., Van Vlierberghe, P., and Vanden Berghe, W. (2025). Epigenetic Rewiring of Protein Kinase Signalling in T-Cell Acute Lymphoblastic Leukaemia. Kinases Phosphatases, 3.","DOI":"10.3390\/kinasesphosphatases3020007"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.2147\/CMAR.S523414","article-title":"Preclinical and Case Series Studies on the Combination of Venetoclax with Epigenetic Drugs in T-Cell Acute Lymphoblastic Leukemia","volume":"17","author":"Zheng","year":"2025","journal-title":"Cancer Manag. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1186\/s40001-024-02108-8","article-title":"Histone deacetylase inhibitors for leukemia treatment: Current status and future directions","volume":"29","author":"Hosseini","year":"2024","journal-title":"Eur. J. Med Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1182\/blood-2017-12-818948","article-title":"The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia","volume":"131","author":"Stein","year":"2018","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13045-020-00937-8","article-title":"EZH2: A novel target for cancer treatment","volume":"13","author":"Duan","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/ijc.35332","article-title":"Targeting the Menin\u2013KMT2A interaction in leukemia: Lessons learned and future directions","volume":"158","author":"Perner","year":"2026","journal-title":"Int. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1182\/blood.2019002457","article-title":"Targeting PRMT1-mediated FLT3 methylation disrupts maintenance of MLL-rearranged acute lymphoblastic leukemia","volume":"134","author":"Zhu","year":"2019","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1182\/blood-2024-210504","article-title":"Multimodal Single-Cell Profiling of Minimal Residual Disease in B Acute Lymphoblastic Leukemia Reveals Genetic and Non-Genetic Factors of Early Drug Resistance","volume":"144","author":"Mehta","year":"2024","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4093","DOI":"10.1182\/bloodadvances.2021005894","article-title":"ALLSorts: An RNA-Seq subtype classifier for B-cell acute lymphoblastic leukemia","volume":"6","author":"Schmidt","year":"2022","journal-title":"Blood Adv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"103030","DOI":"10.1016\/j.ebiom.2020.103030","article-title":"CUP-AI-Dx: A tool for inferring cancer tissue of origin and molecular subtype using RNA gene-expression data and artificial intelligence","volume":"61","author":"Zhao","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1056\/NEJMoa2016272","article-title":"Dasatinib\u2013blinatumomab for Philadelphia chromosome\u2013positive acute lymphoblastic leukemia","volume":"383","author":"Bassan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7001","DOI":"10.1200\/JCO.2021.39.15_suppl.7001","article-title":"Combination of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia: Early results from a phase II study","volume":"39","author":"Short","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3650","DOI":"10.1002\/cncr.30231","article-title":"Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A propensity score analysis","volume":"122","author":"Sasaki","year":"2016","journal-title":"Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0140-6736(21)01222-8","article-title":"KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: Phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study","volume":"398","author":"Shah","year":"2021","journal-title":"Lancet"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T13:14:41Z","timestamp":1775567681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":68,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073335"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073335","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]}}}