{"doi":"10.3389/fonc.2023.1157555","title":"Editorial: The role of the bone marrow microenvironment in multiple myeloma evolution and therapy","abstract":"Mesenchymal stem cells (MSCs) represent an integral part of the BM-ME and promote the proliferation and survival of MM cells. Yet, therapeutic interventions to target MSCs are not clinically available. In their study, Luca Heinemann et al. investigated the transcriptome of MSCs in patients with active MM compared to patients in complete remission (CR) or control subjects. The transcriptome of MSCs from patients with active MM was significantly enriched for genes associated with the PI3K-ACT-mTOR signaling pathway, which was also confirmed at the protein level. Treatment with the pan-PI3K inhibitor pictilisib selectively reduced the growth of MSCs from patients with active MM compared to those from CR or control subjects. Furthermore, pictilisib fully abrogated the proliferation supporting role of MSCs derived from active MM patients on the growth of MM cell lines, highlighting the therapeutic potential of targeting this pathway in the MM BM-ME.Further, Nesreen Amer Ramadan Ali et al. investigated the role of SPARC (secreted protein acidic and rich in cysteine) in myelomagenesis. SPARC is a common stromal motif expressed by follicular dendritic cells. It regulates numerous cellular processes, including immune cell networking and extracellular matrix assembly in lymphoid tissue and BM. The authors show that SPARC expression was significantly higher in primary BM samples compared to lymphoid tissues, and its expression correlated inversely with the level of plasma cell infiltration. In-vitro, co-culture of SPARC-expressing follicular dendritic cells with lymphocytes inhibited the expression of several oncogenes associated with malignant transformation to plasma cells, underscoring an important role of SPARC expression in myelomagenesis.Additionally, this special issue includes two reviews on the BM-ME in MM. Terry Dadzie and Alanna Green elegantly summarize the role of the BM niche in MM survival and evolution. Of particular emphasis is the importance of the BM-ME to allow MM cells to enter a quiescent or dormant state, contributing to treatment evasion and regrowth at a later stage. Daniela Petrusca et al. review recent advances in biological implications of sphingolipid metabolism alterations in MM evolution. Sphingolipids are complex bioactive lipids involved in nearly all cellular functions. Recent studies have emphasized that sphingolipid metabolism and function are significantly altered in the MM BM-ME, which can contribute to the formation of bone lesions and drug resistance. The manuscript also highlights how the aberrant sphingolipid metabolism can be used for prognostic and therapeutic strategies.Taken together, the studies presented in this Research Topic highlight the importance and complexity of the supportive role of the BM-ME in the proliferation, drug resistance, and survival of MM cells. Advancing this research field will ultimately lead to improving prognostic factors and identifying new therapeutic options in MM. We thank all authors who have contributed to this interesting special issue.","journal":"Frontiers in Oncology","year":2023,"id":394187,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":484895,"name":"Niels Weinhold","orcid":"0000-0002-5464-3234","position":1,"is_corresponding":false},{"id":348018,"name":"Jesús Delgado‐Calle","orcid":"0000-0002-2083-2774","position":2,"is_corresponding":false},{"id":469850,"name":"Carolina Schinke","orcid":"0000-0002-2699-1741","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:19:10.334330Z","pmid":"36895479","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}