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Single cell sequencing reveals distinct microenvironment cell types associated with response to high dose melphalan and autologous stem cell transplant in multiple myeloma

ABSTRACT: Single cell sequencing reveals distinct microenvironment cell types associated with response to high dose melphalan and autologous stem cell transplant in multiple myeloma

PROVIDER: PRJNA942019 | ENA |

REPOSITORIES: ENA

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Single cell sequencing reveals distinct microenvironment cell types associated with response to high dose melphalan and autologous stem cell transplant in multiple myeloma

Project description:Single cell sequencing reveals distinct microenvironment cell types associated with response to high dose melphalan and autologous stem cell transplant in multiple myeloma

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Metabolic Changes Contribute to Melphalan Resistance in Multiple Myeloma

Project description:Multiple myeloma is an incurable hematological malignancy that impacts tens of thousands of people every year in the U.S. Treatment for eligible patients includes three stages: induction, consolidation with stem cell rescue, and maintenance. High dose therapy with the DNA alkylating agent, melphalan, remains the primary drug for consolidation therapy in conjunction with autologous stem cell transplant. As a result, melphalan resistance remains a clinical challenge. Here, we use proteometabolomics to examine mechanisms of melphalan resistance in two cell line models. Drug metabolism, steady-state metabolomics, activity-based protein profiling (ABPP), acute treatment metabolomics, and immunoblotting analyses have allowed us to further elucidate metabolic processes contributing to melphalan resistance. Proteometabolomics data indicate that both drug resistant cells have higher levels of pentose phosphate pathway metabolites than their naïve counterparts. Interestingly, we also observed cell line specific changes in purine, pyrimidine and glutathione metabolism that are linked to the differences in steady state metabolism of naïve cells and highlight the heterogeneity of melphalan resistance in these models. Because of the diversity of metabolic changes, our data suggest that omics approaches will be needed to fully examine melphalan resistance in patient specimens and define personalized strategies to optimize the delivery of this therapy.

2020-07-17 | PXD019725 | Pride

Protective effects on melphalan-induced mouse intestinal injury treated by Human Umbilical Cord-derived Mesenchymal Stem Cells

Project description:Autologous peripheral hematopoietic stem cell transplantation (autoHSCT) is one front-line therapy with high-dose melphalan for multiple myeloma (MM). Patients with MM who receive conditioning regimen with melphalan usually suffer from severe gastrointestinal symptoms, as one of nonhematological toxicities. Aim: It is an urgent demand to develop an effective methods to repair the intestinal injuries in patients with MM receiving conditioning regimen with high-dose melphalan for autoHSCT. Therefore, the protective effects of Human umbilical cord derived-mesenchymal stem cells (hucMSCs) is investigated after infusion into mouse model with melphalan-induce gastrointestinal injuries.

2024-04-01 | GSE225899 | GEO

Mechanisms of endothelial injury and transplant-associated thrombotic microangiopathy in tandem autologous hematopoietic stem cell transplant for neuroblastoma

Project description:Our data indicate that endothelial injury is increased in auto-stem cell transplant patients receiving the specific conditioning regimen carboplatin, etoposide and melphalan and is associated with clinical TA-TMA. Moreover, our data identify specific pathways that can be targeted to treat or prevent TA-TMA.

2023-09-11 | GSE227176 | GEO

T-cells' gene expression after high-dose melphalan

Project description:T-cells' transduction efficacy by lentiviral transduction is diminished after high-dose melphalan. To investigate transcriptional changes regarding genes inhibiting viral entry, reverse transcription, nuclear transport and viral genome integration, we performed microarray transcription analysis.

2020-11-23 | GSE148770 | GEO

T-cells' gene expression after high-dose melphalan

Project description:T-cells' gene expression after high-dose melphalan

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Immune Reconstitution After Autologous Hematopoietic Stem Cell Transpl for High-Risk Lymphoma

Project description:RATIONALE: Vaccines may help the body build an effective immune response to kill cancer cells. Giving vaccine therapy after an autologous stem cell transplant may kill any cancer cells that remain after transplant. PURPOSE: This clinical trial is studying how well vaccine therapy works in treating patients who have undergone autologous stem cell transplant for high-risk lymphoma or multiple myeloma.

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Gene expression profiles of patients with multiple myeloma who have been treated previously

Project description:This Series represents the gene expression profiles of patients with multiple myeloma who have been treated previously. In brief, Total Therapy 6 (TT6) is an open label phase 2 protocol for patients with symptomatic multiple myeloma, who had been treated with more than one cycle of prior therapy excluding autologous hematopoietic stem cell transplant. This protocol was approved by the institutional review board on March 25, 2009 (IRB#108053). The TT6 treatment regimen consists of induction therapy with Melphalan/Bortezomib/Thalidomide/Dexamethasone/Cisplatin/Doxorubicin/Cyclophosphamide/Etoposide (M-VTD-PACE) followed by a high dose M-VTD-PACE based tandem transplant. Maintenance therapy consists of Bortezomib/Lenalidomide/Dexamethasone alternating with Borteomib/Melphalan/Dexamethasone every months for 3 years.

2015-01-20 | GSE57317 | GEO

Gene expression profiles of patients with multiple myeloma who have been treated previously

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Mechanisms of endothelial injury and transplant-associated thrombotic microangiopathy in tandem autologous hematopoietic stem cell transplant for neuroblastoma

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