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Advances in nanotechnology have provided novel avenues for the diagnosis and treatment of multiple myeloma (MM), a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow. This review elucidates the potential of nanotechnology to revolutionize myeloma therapy, focusing on nanoparticle-based drug delivery systems, nanoscale imaging techniques, and nano-immunotherapy. Nanoparticle-based drug delivery systems offer enhanced drug targeting, reduced systemic toxicity, and improved therapeutic efficacy. We discuss the latest developments in nanocarriers, such as liposomes, polymeric nanoparticles, and inorganic nanoparticles, used for the delivery of chemotherapeutic agents, siRNA, and miRNA in MM treatment. We delve into nanoscale imaging techniques which provide spatial multi-omic data, offering a holistic view of the tumor microenvironment. This spatial resolution can help decipher the complex interplay between cancer cells and their surrounding environment, facilitating the development of highly targeted therapies. Lastly, we explore the burgeoning field of nano-immunotherapy, which employs nanoparticles to modulate the immune system for myeloma treatment. Specifically, we consider how nanoparticles can be used to deliver tumor antigens to antigen-presenting cells, thus enhancing the body's immune response against myeloma cells. In conclusion, nanotechnology holds great promise for improving the prognosis and quality of life of MM patients. However, several challenges remain, including the need for further preclinical and clinical trials to assess the safety and efficacy of these emerging strategies. Future research should also focus on developing personalized nanomedicine approaches, which could tailor treatments to individual patients based on their genetic and molecular profiles. [ABSTRACT FROM AUTHOR]

Background: The differential signaling and outcome of patients with p190 or p210 transcripts of BCR-ABL1 have been systematically investigated in chronic myeloid leukemia rather than in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Methods: We analyzed the outcomes and ABL1 mutation profiles in 305 consecutive adult patients with Ph+ ALL treated with chemotherapy plus tyrosine kinase inhibitors. We also studied transcriptome features in two newly diagnosed patients with p190 and p210 using single-cell RNA sequencing (scRNA-seq). Results: P190 and p210 were found in 199 (65%) and 106 (35%) patients, respectively. Compared to patients with p190, a higher white blood cell count (p = 0.05), platelet count (p = 0.047), BCR-ABL1 transcript level (p < 0.001), and lower bone marrow blasts (p = 0.003) were found in patients with p210. Patients with p210 had fewer types of ABL1 mutations (4 vs. 16) and a higher prevalence of T315I and E225K/V mutations (91.3% vs. 68.6%; p = 0.031). Patients with p210 had a similar complete remission rate (91.0% vs. 90.1%; p = 0.805) but a lower complete molecular remission rate at 1 month (9.9% vs. 22.0%; p = 0.031) compared with p190. Patients with p210 had lower 3-year overall survival (OS) and disease-free survival (DFS) rates than those with p190 (3-year DFS: 10.4% vs. 9.2%, p = 0.069, 3-year OS: 44.3% vs. 38.2%, p = 0.018, respectively). Multivariate analysis revealed that p210 was independently associated with worse OS [HR 1.692 (95% CI 1.009–2.838), p = 0.046]. Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) was associated with a better prognosis in patients with p210 (p < 0.0001). In addition, scRNA-seq data showed distinct molecular and cellular heterogeneity between bone marrow cells of the two transcripts. Conclusions: Ph+ ALL patients with p190 and p210 had different clinical characteristics, outcomes, ABL1 mutation profiles, and transcriptome features. Allo-HSCT could improve the outcomes of patients with p210. [ABSTRACT FROM AUTHOR]

Background: Myelodysplastic syndrome (MDS) arises from a rare population of aberrant hematopoietic stem and progenitor cells (HSPCs). These cells are relatively quiescent and therefore treatment resistant. Understanding mechanisms underlying their maintenance is critical for effective MDS treatment. Methods: We evaluated microRNA‐126 (miR‐126) levels in MDS patients' sample and in a NUP98‐HOXD13 (NHD13) murine MDS model along with their normal controls and defined its role in MDS HSPCs' maintenance by inhibiting miR‐126 expression in vitro and in vivo. Identification of miR‐126 effectors was conducted using biotinylated miR‐126 pulldown coupled with transcriptome analysis. We also tested the therapeutic activity of our anti‐miR‐126 oligodeoxynucleotide (miRisten) in human MDS xenografts and murine MDS models. Results: miR‐126 levels were higher in bone marrow mononuclear cells from MDS patients and NHD13 mice relative to their respective normal controls (P < 0.001). Genetic deletion of miR‐126 in NHD13 mice decreased quiescence and self‐renewal capacity of MDS HSPCs, and alleviated MDS symptoms of NHD13 mice. Ex vivo exposure to miRisten increased cell cycling, reduced colony‐forming capacity, and enhanced apoptosis in human MDS HSPCs, but spared normal human HSPCs. In vivo miRisten administration partially reversed pancytopenia in NHD13 mice and blocked the leukemic transformation (combination group vs DAC group, P < 0.0001). Mechanistically, we identified the non‐coding RNA PTTG3P as a novel miR‐126 target. Lower PTTG3P levels were associated with a shorter overall survival in MDS patients. Conclusions: MiR‐126 plays crucial roles in MDS HSPC maintenance. Therapeutic targeting of miR‐126 is a potentially novel approach in MDS. [ABSTRACT FROM AUTHOR]