The Role of Marrow Microenvironment in the Growth and Development of Malignant Plasma Cells in Multiple Myeloma

Giannakoulas, Nikolaos; Ntanasis‐Stathopoulos, Ioannis; Terpos, Evangelos

doi:10.3390/ijms22094462

Cited by 54 publications

(45 citation statements)

References 185 publications

(220 reference statements)

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“…Besides, BMSCs have been reported to secrete excessive interleukin-6 (IL-6) to promote and support the growth of MM cells ( Arnulf et al, 2007 ). In addition, another study has revealed that BMSCs could protect MM cells from destruction by reactive cytotoxic T cells (CTL) and NK cells, triggering immune escape ( Giannakoulas et al, 2021 ). In turn, MM cells could also educate and manipulate BMSCs to make a more conducive microenvironment for MM cell growth.…”

Section: Introductionmentioning

confidence: 99%

Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2

Wang

et al. 2022

Front. Cell Dev. Biol.

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Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs). We found that miR-483-5p was highly expressed in MM-MSCs, which may be transported through exosomes from MM-MSCs to MM cells to increase miR-483-5p expression in them. We then investigated the role and mechanism of miR-483-5p in the aggressive progression of MM in vitro. We verified that miR-483-5p promoted MM cell proliferation and reduced apoptosis. Then we predicted and validated that TIMP2, a tumor suppressor gene, is the downstream target of miR-483-5p in MM. In summary, our study indicated that MM-MSCs promote MM malignant progression via the release of exosomes and regulation of miR-483-5p/TIMP2 axis, suggesting an essential role of BMSCs derived exosomal miRNA in MM and a potential marker for MM diagnosis and therapy.

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Section: Introductionmentioning

confidence: 99%

Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2

Wang

et al. 2022

Front. Cell Dev. Biol.

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“…Interestingly, a heterogenous metabolic pattern in baseline positron emission tomography/computed tomography (PET/CT) has been recently associated with adverse prognosis in patients with MM [ 20 ]. Therefore, response to antimyeloma treatment might be indirectly correlated to impaired metabolic status and changes in microenvironment [ 21 , 22 ]. Furthermore, metabolic signatures may have a prognostic value in patients with MM.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Disorders in Multiple Myeloma

Gavriatopoulou

Paschou

Ntanasis‐Stathopoulos

et al. 2021

IJMS

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Multiple myeloma (MM) is the second most common hematological malignancy and is attributed to monoclonal proliferation of plasma cells in the bone marrow. Cancer cells including myeloma cells deregulate metabolic pathways to ensure proliferation, growth, survival and avoid immune surveillance, with glycolysis and glutaminolysis being the most identified procedures involved. These disorders are considered a hallmark of cancer and the alterations performed ensure that enough energy is available for rapid cell proliferation. An association between metabolic syndrome, inflammatory cytokinesand incidence of MM has been also described, while the use of metformin and statins has been identified as a positive prognostic factor for the disease course. In this review, we aim to present the metabolic disorders that occur in multiple myeloma, the potential defects on the immune system and the potential advantage of targeting the dysregulated pathways in order to enhance antitumor therapeutics.

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“…The BM microenvironment has a key supportive role for myeloma growth and progression, with distinct underlying biology at different disease stages [13,15,36,37]. Various BM subsets interact constantly and dynamically with myeloma cells and contribute to the complex immunomodulatory functions induced, as well as drug refractoriness [38,39].…”

Section: Discussionmentioning

confidence: 99%

Aberrant Plasma Cell Contamination of Peripheral Blood Stem Cell Autografts, Assessed by Next-Generation Flow Cytometry, Is a Negative Predictor for Deep Response Post Autologous Transplantation in Multiple Myeloma; A Prospective Study in 199 Patients

Kostopoulos

Eleutherakis‐Papaiakovou

Rousakis

et al. 2021

Cancers

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High-dose chemotherapy with autologous stem cell support (ASCT) is the standard of care for eligible newly diagnosed Multiple Myeloma (MM) patients. Stem cell graft contamination by aberrant plasma cells (APCs) has been considered a possible predictive marker of subsequent clinical outcome, but the limited reports to date present unclear conclusions. We prospectively estimated the frequency of graft contamination using highly sensitive next-generation flow cytometry and evaluated its clinical impact in 199 myeloma patients who underwent an ASCT. Contamination (con+) was detected in 79/199 patients at a median level 2 × 10−5. Its presence and levels were correlated with response to induction treatment, with 94%, 71% and 43% achieving CR, VGPR and PR, respectively. Importantly, con+ grafts conferred 2-fold and 2.8-fold higher patient-risk of not achieving or delaying reaching CR (4 vs. 11 months) and MRD negativity (5 vs. 18 months) post ASCT, respectively. Our data also provide evidence of a potentially skewed bone marrow (BM) reconstitution due to unpurged grafts, since con+ derived BM had significantly higher prevalence of memory B cells. These data, together with the absence of significant associations with baseline clinical features, highlight graft contamination as a potential biomarker with independent prognostic value for deeper responses, including MRD negativity. Longer follow-up will reveal if this corresponds to PFS or OS advantage.

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The Role of Marrow Microenvironment in the Growth and Development of Malignant Plasma Cells in Multiple Myeloma

Cited by 54 publications

References 185 publications

Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2

Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2

Metabolic Disorders in Multiple Myeloma

Aberrant Plasma Cell Contamination of Peripheral Blood Stem Cell Autografts, Assessed by Next-Generation Flow Cytometry, Is a Negative Predictor for Deep Response Post Autologous Transplantation in Multiple Myeloma; A Prospective Study in 199 Patients

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