{
  "abstract": "Background Melanoma demonstrates early systemic dissemination, including colonization of the bone marrow, where disseminated tumor cells disrupt hematopoietic homeostasis. Although immune checkpoint inhibitor therapy has revolutionized melanoma outcomes, its effects on bone marrow biology and hematopoietic stem cell function remain poorly defined. Emerging evidence suggests that melanoma tumor cells and immune checkpoint inhibitors synergistically impair hematopoietic regulation, leading to lineage skewing, cytopenias, and increased risk of therapy-related myeloid neoplasms. This review synthesizes mechanistic, clinical, and biotechnology-enabled evidence on bone marrow remodeling and hematologic dysfunction in melanoma.Methods A comprehensive literature review was conducted using PubMed, Scopus, and Embase. Studies included mechanistic models, clinical reports, and cohort-based or genomic investigations on bone marrow dysfunction, clonal hematopoiesis, or therapy-related myeloid neoplasms in melanoma. Priority was given to studies employing biotechnology platforms such as single-cell RNA sequencing, mass cytometry (CyTOF), and next-generation sequencing to define bone marrow niche alterations and hematopoietic clonal dynamicsResults Melanoma tumor cells infiltrate the bone marrow early, with disseminated tumor cells detected in up to 57 percent of patients with stage I to III disease. These cells exploit hematopoietic trafficking signals and disrupt stromal-stem cell interactions, initiating inflammatory remodeling. Single-cell RNA sequencing and mass cytometry have demonstrated expansion of myeloid-derived suppressor cells, suppression of erythroid and B-lymphoid differentiation, and elevated interleukin-3 signaling that promotes myeloid skewing. Immune checkpoint inhibitors further disrupt bone marrow regulation by applying selective pressure on hematopoietic stem cells. Longitudinal next-generation sequencing and liquid biopsy analyses have revealed expansion of pre-leukemic clones, particularly with DNMT3A and TET2 mutations. Case studies and systems immunology analyses document development of myelodysplastic syndromes during immune checkpoint therapy. Although large-scale data show no statistically significant increase in overall therapy-related myeloid neoplasm incidence, a 1.82-fold higher risk is observed in patients with baseline cytopenias or combination immunotherapy exposureConclusions Melanoma tumor cells and immune checkpoint inhibitors cooperatively reprogram the bone marrow niche, resulting in early hematopoietic dysfunction and increased risk of therapy-related myeloid neoplasms. Biotechnology tools now enable earlier detection, clonal monitoring, and intervention, supporting precision strategies to prevent immunotherapy-associated hematologic toxicity",
  "authors": [
    {
      "affiliations": [
        "UAMS Northwest Regional Campus, Fayetteville, AR, USA",
        "University of Arkansas, Fayetteville, AR, USA"
      ],
      "name": "Chinemerem M Emeasoba"
    },
    {
      "affiliations": [
        "Northeast Georgia Medical Center, Atlanta, GA, USA"
      ],
      "name": "Chiugo Okoye"
    },
    {
      "affiliations": [
        "UAMS Northwest Regional Campus, Fayetteville, AR, USA"
      ],
      "name": "Cade Richesin"
    },
    {
      "affiliations": [
        "Tennova Health, Powell, TN, USA"
      ],
      "name": "Oluwafemifola Oyedeji"
    },
    {
      "affiliations": [
        "UAMS Northwest Regional Campus, Fayetteville, AR, USA"
      ],
      "name": "Zeytun M Guyon"
    },
    {
      "affiliations": [
        "Tulane University School of Medicine, New Orleans, LA, USA"
      ],
      "name": "Chiamaka Nwachukwu"
    },
    {
      "affiliations": [
        "UAMS Northwest Regional Campus, Fayetteville, AR, USA"
      ],
      "name": "Hannah M Jensen"
    }
  ],
  "title": "776 Melanoma tumor cells and immunotherapy cooperatively reprogram bone marrow niches to induce early hematopoietic dysfunction and therapy-related myeloid neoplasms",
  "uid": "21cfadce-f484-5517-bf57-2b2915469e19"
}