{
  "abstract": "Background: A previous study by Castro et al. (2024) identified, through artificial intelligence-based screening approaches, a significant association between PTP4A3 expression and the prognosis of patients with acute myeloid leukemia (AML). Subsequent investigations conducted by our research group demonstrated that in vitro inhibition of PTP4A3 reduced cell viability and clonogenic potential while inducing apoptosis and cell cycle arrest, consistent with findings reported in other malignancies. Aim: Based on these observations, we sought to characterize the molecular network associated with PTP4A3 expression through the integration of multi-method evidence. Materials and Methods: Multi-omics analyses were performed in an expanded primary AML cohort (n=304), including survival analyses, differential expression analyses of transcriptomic, proteomic, and phosphoproteomic datasets, functional enrichment analyses (ORA/GSEA), transcription factor activity inference, immune deconvolution, weighted gene co-expression network analysis (WGCNA), and multi-omics integration using the DIABLO and MOFA frameworks. The resulting datasets were subsequently integrated to identify molecular mechanisms associated with PTP4A3 expression. A panel of AML cell lines was used to evaluate PTP4A3 mRNA and protein expression levels by qPCR and Western blotting. Statistical analyses included Student’s t-test, ANOVA, Kruskal–Wallis test, Kaplan–Meier survival analysis, multivariate Cox regression, and the log-rank test (p<0.05). Results: The integration of complementary in silico and in vitro approaches identified several genes consistently and positively associated with PTP4A3 expression across multiple analytical methods, including MEIS1, HOXA9, RHOC, SORBS3, TNS3, ABI2 and RAB13, CYP2S1, and LILRB4. Conversely, a negative association was observed with ZBTB7A, a transcription factor involved in cellular differentiation. Pathway-level analyses further linked PTP4A3 expression to TNF-α and MAPK/ERK signaling, HOXA9–MEIS1/KMT2A-like transcriptional programs, leukemic stem cell signatures, erythroid suppression, epithelial–mesenchymal transition, migration and cytoskeletal remodeling, angiogenesis, as well as monocytic/monoblastic differentiation programs. Consistently, qPCR and Western blot analyses demonstrated higher PTP4A3 expression and protein abundance in less differentiated AML cell lines. Discussion and conclusions: The convergence of multiple analytical approaches revealed a coordinated and statistically robust molecular axis centered on PTP4A3, characterized by the concomitant expression of MEIS1, HOXA9/HOXB3/HOXA5/HOXA10, KMT2A transcriptional activity, RHOC, and a network of cytoskeletal scaffold proteins (SORBS3, TNS3, ABI2, and RAB13). The presence of BAALC, MN1, and CD34 within the DIABLO-derived network provides important cross-validation, linking the PTP4A3-high phenotype to well-established AML prognostic markers. Moreover, PTP4A3 expression was enriched in poorly differentiated AML cell lines, and its inhibition interfered with apoptotic and MAPK/ERK signaling pathways, corroborating the in silico findings and reinforcing its potential as a biomarker and therapeutic target in AML.",
  "abstract_shown": true,
  "affiliations": [
    "Universidade de São Paulo (USP), São Paulo, SP, Brazil",
    "Universidade de Pernambuco (UPE), Pernambuco, PE, Brazil",
    "Universidade Federal de São Carlos (UFSCar), Sorocaba, SP, Brazil",
    "University of Pittsburgh, United States"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Natália Sudan PARDUCCI"
    },
    {
      "affs": [
        1
      ],
      "name": "Juan Luiz COELHO-SILVA"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Fernanda Lopes CARVALHO"
    },
    {
      "affs": [
        2
      ],
      "name": "Giovanna A CASTRO"
    },
    {
      "affs": [
        2
      ],
      "name": "Tiago Agostinho ALMEIDA"
    },
    {
      "affs": [
        3
      ],
      "name": "Peter WIPF"
    },
    {
      "affs": [
        0
      ],
      "name": "João Agostinho MACHADO-NETO"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c6m656vye4w1n.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107639",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926013866",
  "id": "c6m656vye4w1n",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107639",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7223130914",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/c6m656vye4w1n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "029efc0ffd044de2b92a55f3b8e39fde",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.107639"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "MULTI-OMICS EVIDENCE SUPPORTS A POTENTIAL ROLE FOR PTP4A3 IN ACUTE MYELOID LEUKEMIA BIOLOGY",
  "title_text": "MULTI-OMICS EVIDENCE SUPPORTS A POTENTIAL ROLE FOR PTP4A3 IN ACUTE MYELOID LEUKEMIA BIOLOGY",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:24Z",
  "url": "https://research.draconitic.com/paper/c6m656vye4w1n",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}