The Future of Precision Oncology

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12613 - 12613

Published: Aug. 9, 2023

Our understanding of the molecular mechanisms underlying cancer development and evolution have evolved rapidly over recent years, variation from one patient to another is now widely recognized. Consequently, one-size-fits-all approaches treatment been superseded by precision medicines that target specific disease characteristics, promising maximum clinical efficacy, minimal safety concerns, reduced economic burden. While oncology has very successful in some tumors with a large number patients do not yet access for their disease. The success next-generation depends on discovery new actionable rapid, accurate, comprehensive diagnosis complex phenotypes within each patient, novel trial designs improved response rates, worldwide targeted anticancer therapies all patients. This review outlines current technological trends, highlights multidisciplinary efforts are underway ensure many more will be able benefit near future.

Language: Английский

---

Omics approaches: Role in acute myeloid leukemia biomarker discovery and therapy

Cancer Genetics, Journal Year: 2025, Volume and Issue: 292-293, P. 14 - 26

Published: Jan. 5, 2025

Language: Английский

---

Divergent Processing of Cell Stress Signals as the Basis of Cancer Progression: Licensing NFκB on Chromatin

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8621 - 8621

Published: Aug. 7, 2024

Inflammation is activated by diverse triggers that induce the expression of cytokines and adhesion molecules, which permit a succession molecules cells to deliver stimuli functions help immune system clear primary cause tissue damage, whether this an infection, tumor, or trauma. During inflammation, short-term changes in secretion strong mediators inflammation occur, while long-term occur specific groups cells. Long-term include cellular transdifferentiation for some types need regenerate damaged tissue, as well death can be detrimental integrity if they remain active beyond boundaries essential function. The transcriptional regulator NFκB enables fundamental gene during development. recurrence malignant disease, cell stress-induced alterations enable growth cancer clones are substantially resistant therapeutic intervention system. A number those due significant defects feedback signal cascades control activity NFκB. Specifically, stress contributes it overrides modules otherwise protect host tissue. involved both suppression promotion cancer, key distinctive feature determines its net effect remains unclear. This paper aims provide answer at least one aspect question, namely mechanism divergent response critical inflammatory general.

Language: Английский

---

Role of Artificial Intelligence in Identifying Vital Biomarkers with Greater Precision in Emergency Departments During Emerging Pandemics

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 722 - 722

Published: Jan. 16, 2025

The COVID-19 pandemic has accelerated advances in molecular biology and virology, enabling the identification of key biomarkers to differentiate between severe mild cases. Furthermore, use artificial intelligence (AI) machine learning (ML) analyze large datasets been crucial for rapidly identifying relevant disease prognosis, including COVID-19. This approach enhances diagnostics emergency settings, allowing more accurate efficient patient management. study demonstrates how algorithms departments can identify vital prognosis an emerging using as example by analyzing clinical, epidemiological, analytical, radiological data. All consecutively admitted patients were included, than 89 variables processed Random Forest (RF) algorithm. RF model achieved highest balanced accuracy at 92.61%. most predictive mortality included procalcitonin (PCT), lactate dehydrogenase (LDH), C-reactive protein (CRP). Additionally, system highlighted significance interstitial infiltrates chest X-rays D-dimer levels. Our results demonstrate that is critical diseases, accelerating data analysis, optimizing personalized treatment, emphasizing importance PCT LDH high-risk patients.

Language: Английский

---

Phosphoproteomics identifies determinants of PAK inhibitor sensitivity in leukaemia cells

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 13, 2025

Abstract Background The P21 activated kinases (PAK) are frequently dysregulated in cancer and have central roles oncogenic signalling, prompting the development of PAK inhibitors (PAKi) as anticancer agents. However, such compounds not reached clinical use because, at least partially, there is a limited mechanistic understanding their mode action. Here, we aimed to characterize functional molecular responses PAKi (PF-3758309, FRAX-486 IPA-3) multiple acute myeloid leukaemia (AML) models gain insights on biochemical pathways affected by these this disease identify determinants response patient samples. Methods We mined phosphoproteomic datasets primary AML, used proteomics phosphoproteomics profile impact immortalized (P31/Fuj MV4-11), AML cells from 8 patients. These omics were integrated with gene dependency data which proteins targeted necessary for proliferation AML. studied effect cell cycle progression, proliferation, differentiation apoptosis. Finally, input machine learning that predicted ex vivo two independent (with 36 50 cases, respectively) PF-3758309 markers response. Results found PAK1 activation– measured data– was predictive poor prognosis cases. most effective reducing inducing apoptosis lines. In lines cells, inhibited PAK, AMPK PKCA activities, reduced c-MYC transcriptional activity expression ribosomal proteins, FLT3 pathway FLT3-ITD mutated cells. STAT5 phosphorylation Tyr699. Functionally, cell-growth, induced apoptosis, blocked progression promoted model-dependent manner. ML modelling accurately classified samples sensitive or resistant treatment, highlighted PHF2 Ser705 robust biomarker. Conclusions summary, our define proteomic, immortalised suggest route personalise treatments based inhibitors.

Language: Английский

---

Genetic Profiling of Acute and Chronic Leukemia via Next-Generation Sequencing: Current Insights and Future Perspectives

Hematology Reports, Journal Year: 2025, Volume and Issue: 17(2), P. 18 - 18

Published: March 28, 2025

Leukemia is a heterogeneous group of hematologic malignancies characterized by distinct genetic and molecular abnormalities. Advancements in genomic technologies have significantly transformed the diagnosis, prognosis, treatment strategies for leukemia. Among these, next-generation sequencing (NGS) has emerged as powerful tool, enabling high-resolution profiling that surpasses conventional diagnostic approaches. By providing comprehensive insights into mutations, clonal evolution, resistance mechanisms, NGS revolutionized precision medicine leukemia management. Despite its transformative potential, clinical integration presents challenges, including data interpretation complexities, standardization issues, cost considerations. However, continuous advancements platforms bioinformatics pipelines are enhancing reliability accessibility routine practice. The expanding role paving way improved risk stratification, targeted therapies, real-time disease monitoring, ultimately leading to better patient outcomes. This review highlights impact on research applications, discussing advantages over traditional techniques, key approaches, emerging challenges. As oncology continues evolve, expected play an increasingly central diagnosis management leukemia, driving innovations personalized therapeutic interventions.

Language: Английский

---

High Mitochondrial Protein Expression as a Potential Predictor of Relapse Risk in Acute Myeloid Leukemia Patients with the Monocytic FAB Subtypes M4 and M5

Cancers, Journal Year: 2023, Volume and Issue: 16(1), P. 8 - 8

Published: Dec. 19, 2023

AML is a highly aggressive and heterogeneous form of hematological cancer. Proteomics-based stratification patients into more refined subgroups may contribute to precise characterization the patient-derived cells. Here, we reanalyzed liquid chromatography-tandem mass spectrometry (LC-MS/MS) generated proteomic phosphoproteomic data from 26 FAB-M4/M5 patients. The achieved complete remission after induction therapy. Twelve them later developed chemoresistant relapse (RELAPSE), 14 were relapse-free (REL_FREE) long-term survivors. We considered not only RELAPSE REL_FREE characteristics but also integrated French-American-British (FAB) classification, along with considering presence nucleophosmin 1 (NPM1) mutation cytogenetically normal AML. found significant number differentially enriched proteins (911) phosphoproteins (257) between various FAB subtypes in Patients myeloblastic M1/M2 subtype showed higher levels RNA processing-related routes lower signaling related terms like translation degranulation when compared M4/M5 subtype. Moreover, that high abundance associated mitochondrial oxidative phosphorylation, particularly observed NPM1 mutated subgroup, distinguishes relapsing non-relapsing patient cells M4/M5. Thus, discovery subtype-specific biomarkers through profiling complement existing classification system for potentially aid selecting personalized treatment strategies individual

Language: Английский

---

Clinical Proteomics: A Promise Becoming Reality

Molecular & Cellular Proteomics, Journal Year: 2024, Volume and Issue: 23(2), P. 100688 - 100688

Published: Jan. 27, 2024

Methods to Discover and Validate Biofluid-Based Biomarkers in Neurodegenerative DementiasMolecular & Cellular ProteomicsVol. 22Issue 10PreviewIn Brief We review technologies used for body fluid protein biomarker discovery translation clinical practice. address their main characteristics, use research clinics, strengths limitations, a future perspective. Full-Text PDF Open AccessThe First Pituitary Proteome Landscape From Matched Anterior Posterior Lobes Better Understanding of the GlandMolecular 1PreviewIn Our study first pituitary proteome draft offers following novelty; time, we present an extensive proteomic database containing proteins from both anterior posterior lobes healthy pituitary, identifying various pituitary-enriched lobe specificities, followed by target verification hormones; are describing three uPE1 have demonstrated that S100 proteins, which known markers adenomas, showed presence significantly lobe. AccessSARS-CoV-2 Variants Show Different Host Cell Profiles With Delayed Immune Response Activation Omicron-Infected CellsMolecular 5PreviewIn SARS-CoV-2 has mutated over past years numerous variants concern (VOCs). Employing quantitative whole-cell proteomics, elucidate host cell immune responses upon infection with ancestral B.1, VOCs Delta, Omicron BA.1 strains. Molecular assays further illustrate reduced viral levels delayed pathway response when compared B.1 Delta. Overall, this insights into profiles distinct kinetics AccessProteomic Characterization Acute Myeloid Leukemia Precision MedicineMolecular 4PreviewIn Proteomic genomic studies identified new drug targets acute myeloid leukemia (AML), leading therapeutic options certain patient subpopulations. In addition, many other drugs advanced stages development proteomics keeps uncovering interest. Given large number therapies likely be available AML near future, identification signatures each will key select best treatment given patient. AccessSensitive, High-Throughput HLA-I HLA-II Immunopeptidomics Using Parallel Accumulation-Serial Fragmentation Mass SpectrometryMolecular 6PreviewIn In-depth mass spectrometry–based profiling human leukocyte antigen (HLA) peptides currently requires amounts sample, off-line fractionation is frequently improve coverage. However, primary tissues often input limited therefore not amenable such workflows. Here, developed optimized single-shot acquisition strategy on timsTOF single-cell sensitive high-throughput immunopeptidome analysis. demonstrate >2-fold increase identfied propose multiple collision energy slopes samples different peptide-binding motifs. AccessProspective Imaging Spectrometry Clinical DiagnosticsMolecular 9PreviewIn spectrometry emerging technology applications it provides spatial molecular data within tissue biopsy diagnoses prognoses. This article considers aspects imaging-based include analyte selection, quality control/assurance metrics, reproducibility, classification, scoring. AccessCross-Linking Uncovers Interactions Between High-Density Lipoproteins Spike GlycoproteinMolecular 8PreviewIn Here utilized cross-linking (XL-MS) investigate circulating interaction networks context SARS-CoV-2. The spike glycoprotein was determined interact high-density lipoprotein including ApoD. between ApoD confirmed cells through affinity purification-MS. XL-MS recombinant ApoD, coupled structural modeling, receptor-binding domain. overexpression cultured lines did influence replication or infection. AccessUncovering Protein Networks Cardiovascular ProteomicsMolecular article, critically assess existing methods reconstructing discuss method preferred cardiovascular research. necessity reconstruct separately type disease entity provide illustrative examples importance taking consideration relevant post-translational modifications. Finally, how findings could interpreted using RNA-sequencing data. AccessFunctional Impact Protein–RNA Variation Cancer AnalysesMolecular 7PreviewIn Proteogenomic cancer highlight broad protein–RNA discrepancies. Tumor Analysis Consortium (CPTAC) mRNA eight indications, show impact low RNA–protein correlations biological processes, signaling pathways, targets. lead suggesting protein-based subtyping may unravel features seen RNA measurements. These analyses critical role phenotypic tumor characterization. AccessMass Spectrometry–Based Proteomics Epithelial Ovarian Cancers: A PerspectiveMolecular systematically reviewed MS-based epithelial ovarian cancer, 2000 trials since 1990. None been adopted clinic, none firstly discovered phase 3 4. Stringent standards design required, more in-depth dysregulated essential. AccessClinical Solid Organ TissuesMolecular 11PreviewIn For years, immunohistochemistry tool pathology localization quantification solid tissues, but poorly standardized suffers practical limitations. field ripe novel complementary help diagnosis. perspective focuses issues hampering highlights liquid chromatography-tandem particular well-positioned complement testing. also where guidance needed ensure rigor environments. AccessIntegrated Understand Role Neuritin (NRN1) as Mediator Cognitive Resilience Alzheimer's DiseaseMolecular Mechanisms individuals (AD) avoid dementia well known. employed multiplex tandem tag (TMT-MS)–based identify linked cognitive resilience AD. Computational strategies NRN1 synaptic associated resilience. models AD, can facilitate dendritic spine against amyloid-β (Aβ) block Aβ-induced neuronal hyperexcitability. assessed alters TMT-MS, revealed overlapping synapse-related biology humans. Exploration Pancreatic CancerMolecular extremely lethal options. Identifying effective early-detection biomarkers urgently needed. review, describe recent advances functional pancreatic cancer. Regarding modifications–mediated intracellular signaling, ligands plasma membrane receptors–mediated intercellular signaling. terms bulk diagnostic studying heterogeneity. AccessMulti-Omics Profiling HealthMolecular Current medical care treating people after they become patients rather than preventing illness, high costs chronic late-stage diseases. Additionally, "one-size-fits all" approach healthcare does take account individual differences genetics, environment, lifestyle factors, decreasing benefiting interventions. Rapid multi-omics enabled deep phenotyping, empowers precision health approaches poised transform healthcare. AccessTen Years Extracellular Matrix Proteomics: Accomplishments, Challenges, Future PerspectivesMolecular extracellular matrix (ECM) complex assembly hundreds forming architectural organizer multicellular organisms. Over decade, bottom-up choice profile composition ECM. reviews state art ECM illustrates emerged powerful pipeline biomarkers. introduces resources proteomics. AccessUltrasensitive Detection Technologies Vesicle MeasurementsMolecular To harness full potential vesicles (EVs) applications, necessary find appropriate enable selective isolation rare subpopulations EVs. Many conventional detection sensitivity detect abundance EVs, limiting EV perspective, current ultrasensitive technologies, areas growth future. Glyco(proteo)mics increasingly mature toolbox glycomic- glycoproteomic applied biopharmaceuticals evaluation glycobiomarkers fields. glycoproteomics, parallel made earlier proposed tiers spectrometry. Multimarker readouts foreseen longitudinal sampling monitoring glycomic diagnosis monitoring. accurate multimarker panel discussed. AccessProteome Mapping Human Islet Microenvironment Reveals Endocrine–Exocrine Signaling Sphere InfluenceMolecular our Microdroplet Processing One pot Trace Samples (microPOTS) TMT platform islet microenvironment pancreas. were able quantify 6000 seven regions same enhancements computational extract hypotheses first-of-its-kind dataset. addition recapitulating functions islet, specific processing activities heterogeneity expression. AccessPlasma Kinetics ExerciseMolecular After measuring 4163 before, during, 1-h treadmill exercise 75 middle-aged adults, found 765 changed at peak exercise, majority these returned baseline after. Of 56 sustained change rest, there enrichment secreted association cardiometabolic traits independent cohort, promising candidates investigation. AccessDissecting Detergent-Insoluble Disease TMTc-Corrected Quantitative TMT-LC/LC–MS/MS TMTc-based correct ratio compression, analyzed detergent-insoluble 30 AD control brain samples. 84 enriched fraction, accumulated mostly low-complexity regions. pathological hallmarks resistant detergent extraction, providing list pathways exclusively proteome. AccessMS-Based Body Fluids: End BeginningMolecular its nature suited routine measurement held back technological conceptual constraints. improvements throughput, streamlining, robustness, progressively overcoming constraints recently success stories. Cutting-edge scan modes, multiplexing, sample preparation promise enhance technology, envision finally bring clinic. AccessAn Inflection Point Biomarkers: What What's NextMolecular highest value proposition medicine today. Despite progress sciences evolving regulatory frameworks biomarkers, about improving health. Achieving necessitates moving away reductionist thinking diseases adaptive systems defining representations system states. redefining communication, ultimately prove game changing who benefit. Atlas Knee Joint Proteins Their Osteoarthritis Defined Literature MiningMolecular Information gathered analysis knee joint essential management osteoarthritis, most prevalent rheumatic pathology. Pursuing one goals Project, systematic based literature mining define atlas organ, prioritization cited representative tissues. Pathway depicted processes contributing OA pathophysiology. AccessProteomics: Progress Promise Chronic Kidney Population genetics leverage large-scale accuracy tools kidney disease. Access "Clinical proteomics" understood encompass spectrum activity pre-clinical diagnostics: clinically materials; addressing question need; (MS)-based proteomics-derived tests reference laboratory informing decision-making. widely explore basis disease, targetable intervention, predict outcome response, probe resistance mechanisms. special issue presents wide range research, reviews, perspectives pertaining expanding scope reflected foci represented, neurodegenerative (1Teunissen C.E. Kimble L. Bayoumy S. Bolsewig K. Burtscher F. Coppens et al.MIRIADE consortium. discover validate biofluid-based dementias.Mol. Proteomics. 2023; 22100629Abstract Full Text Scopus (3) Google Scholar, 2Gobom J. Brinkmalm A. G. Blennow Zetterberg H. targeted spectrometry.Mol. 2024; 23 (100721)Google 3Hurst C. Pugh D.A. Abreha M.H. Duong D.M. Dammer E.B. Bennett al.Integrated understand neuritin mediator disease.Mol. 22100542Abstract (2) 4Zaman M. Fu Y. Chen P.C. Sun Yang Wu Z. al.Dissecting TMTc-corrected 22100608Abstract Scholar), infectious (5Burnap S.A. Ortega-Prieto A.M. Jimenez-Guardeño J.M. Ali Takov Fish al.Cross-linking uncovers interactions lipoproteins glycoprotein.Mol. 22100600Abstract (0) 6Metzler Tharyan R.G. Klann Grikscheit Bojkova D. Cinatl al.SARS-CoV-2 activation omicron-infected cells.Mol. 22100537Abstract (1) endocrinology (7Banerjee Biswas Barpanda Halder Sibal Kattimani R. al.The landscape matched better understanding gland.Mol. 22100478Abstract PubMed 8Gosline S.J.C. Veličković Pino J.C. Day L.Z. Attah I.K. Swensen A.C. al.Proteome mapping reveals endocrine-exocrine sphere influence.Mol. 22100592Abstract (9Hasman Mayr Theofilatos Uncovering proteomics.Mol. 22100607Abstract inflammatory (10Paz-González Lourido Calamia V. Fernández-Puente P. Quaranta Picchi al.An osteoarthritis defined mining.Mol. 22100606Abstract (11Schlosser Grams M.E. Rhee E.P. 22100550Abstract (12Huang Gao W. Tian Functional exploration cancer.Mol. 22100575Abstract 13Casado Cutillas P.R. characterization medicine.Mol. 22100517Abstract (4) 14Arad Geiger T. protein-RNA variation analyses.Mol. 22100587Abstract 15Qian Xue Guo spectrometry-based cancers: perspective.Mol. 22100578Abstract burgeoning (16Mi M.Y. Barber J.L. Rao Farrell L.A. Sarzynski M.A. Bouchard al.Plasma exercise.Mol. 22100601Abstract 17Babu Snyder Multi-omics health.Mol. 22100561Abstract (13) Scholar). part instrumentation, methodologies, capabilities. Methodological allowed detailed challenging materials like (18Naba Ten proteomics: accomplishments, challenges, perspectives.Mol. 22100528Abstract Scholar) CNS (4Zaman (EV) payloads driven robust (19Shami-Shah Norman Walt D.R. Ultrasensitive vesicle measurements.Mol. 22100557Abstract immunopeptidomics inform immunological guide vaccine expanded owing optimization (20Phulphagar K.M. Ctortecka Jacome A.S.V. Klaeger Verzani E.K. Hernandez G.M. al.Sensitive, accumulation-serial fragmentation 22100563Abstract remains workhorse contemporary scale array-based make them attractive alternative 16Mi Complex cross-sectional, multi-omic facilitated accelerating computer speeds, storage capabilities, promulgation focused (17Babu 18Naba Improved sample-handling instrument contributed expansion spatially-resolved (8Gosline Prior limitations prevented numbers being greatly highly multiplexed (3Hurst far MS systems, scanning acquisition. Targeted reaction application modifications assessing stage effects drugs. largely purposes candidate preclinical measure peptide PTM-modified related imaging explored augment replace histopathologic suite (21Moore Patterson N.H. Norris Caprioli R.M. Prospective diagnostics.Mol. 22100576Abstract 22Phipps W.S. Kilgore M.R. Kennedy J.J. Whiteaker J.R. Hoofnagle A.N. Paulovich A.G. organ tissues.Mol. 22100648Abstract especially important deepening perturbations posttranslational phosphorylation, ubiquitylation, acetylation, sumoylation, glycosylation. now PTMs scale, individually serial yielding global exactly thereby facilitating integration while sparing precious material. Such comprehensive portraits much alone. Bottlenecks lack access annotation follow-up information integrated slowly proteogenomics enhancing becomes ever clearer (23Mani Krug Zhang B. Satpathy Clauser K.R. Ding al.Cancer proteogenomics: prospects.Nat. Rev. Cancer. 2022; 22: 298-313Crossref (56) While initially overhyped, considerable evidence techniques depth, reproducibility required aid diagnosis, prognosis, clinically-actionable prediction 24Bader Albrecht Mann fluids: end beginning.Mol. 22100577Abstract (5) 25Barker A.D. Alba M.M. Mallick Agus D.B. Lee J.S.H. An inflection point biomarkers: what what's next.Mol. 22100569Abstract 26van der Burgt Wuhrer glyco(proteo)mics 22100565Abstract needs additional validation, assay refinement, economics assessment, viable reimbursement remain challenges deployment problems clinic works progress, papers demonstrate, greater ever, likelihood having direct, positive interventions precise therapies. member scientific advisory boards Kymera, PTM BioLabs, Seer. G members board PrognomIQ. work supported grants P01CA206978 S.A.C. NIH, U24CA270823 U01CA271402 C U24-CA271075 National Institute (NCI) program, Swiss Science Foundation (SNF) grant CRSII5_186405 C., Dr Miriam Sheldon Adelson Medical Research thank entire Broad group valuable discussions.

Language: Английский

---

Impact of p53-associated acute myeloid leukemia hallmarks on metabolism and the immune environment

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 5, 2024

Acute myeloid leukemia (AML), an aggressive malignancy of hematopoietic stem cells, is characterized by the blockade cell differentiation, uncontrolled proliferation, and expansion that impairs healthy hematopoiesis results in pancytopenia susceptibility to infections. Several genetic chromosomal aberrations play a role AML influence patient outcomes. TP53 key tumor suppressor gene involved variety features, such as cell-cycle regulation, genome stability, stem-cell homeostasis, apoptosis, metabolism, senescence, repair DNA damage response cellular stress. In AML, alterations occur 5%-12% de novo cases. These mutations form important molecular subgroup, patients with these have worst prognosis shortest overall survival among even when treated chemotherapy allogeneic transplant. The frequency TP53-mutations increases relapsed recurrent associated chemoresistance. Progress genetics biology has brought novel therapies, however, clinical benefit agents for whose disease driven remains largely unexplored. This review focuses on characteristics TP53-mutated disease; impact selected hallmarks leukemia, particularly metabolic rewiring immune evasion, importance mutations; current progress development preclinical therapeutic strategies treat disease.

Language: Английский

---

Phosphoproteomic Characterization and Kinase Signature Predict Response to Venetoclax Plus 3+7 Chemotherapy in Acute Myeloid Leukemia

Advanced Science, Journal Year: 2023, Volume and Issue: 11(11)

Published: Dec. 31, 2023

Abstract Resistance to chemotherapy remains a formidable obstacle in acute myeloid leukemia (AML) therapeutic management, necessitating the exploration of optimal strategies maximize benefits. Venetoclax with 3+7 daunorubicin and cytarabine (DAV regimen) young adult de novo AML patients is evaluated. 90% treated achieved complete remission, underscoring potential this regimen as compelling intervention. To elucidate underlying mechanisms governing response DAV AML, quantitative phosphoproteomics discern distinct molecular signatures characterizing subset DAV‐sensitive used. Cluster analysis reveals an enrichment phosphoproteins implicated chromatin organization RNA processing within DAV‐susceptible DA‐resistant patients. Furthermore, kinase activity profiling identifies AURKB candidate indicator efficacy due activation. Intriguingly, cells overexpressing exhibit attenuated MCL ‐1 expression, rendering them receptive treatment maintaining resistant DA treatment. Moreover, dataset delineates shared kinase, AKT1, associated response. Notably, AKT1 inhibition augments antileukemic AML. Overall, phosphoproteomic study role predictive biomarker for DA, but not DAV, resistance proposes promising strategy counteract therapy

Language: Английский

---