Identification and Characterization of Multiple Myeloma Stem Cell-Like Cells

Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.

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Characterization of hematopoietic stem cell subsets from patients with multiple myeloma after mobilization with plerixafor

Cytotherapy ◽

10.3109/14653249.2010.530652 ◽

2011 ◽

Vol 13 (4) ◽

pp. 459-466 ◽

Cited By ~ 27

Author(s):

Isabel Taubert ◽

Rainer Saffrich ◽

Abraham Zepeda-Moreno ◽

Isabelle Hellwig ◽

Volker Eckstein ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem

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PIWIL1 Drives Chemoresistance in Multiple Myeloma by Modulating Mitophagy and the Myeloma Stem Cell Population

Frontiers in Oncology ◽

10.3389/fonc.2021.783583 ◽

2022 ◽

Vol 11 ◽

Author(s):

Yajun Wang ◽

Lan Yao ◽

Yao Teng ◽

Hua Yin ◽

Qiuling Wu

Keyword(s):

Multiple Myeloma ◽

Drug Resistance ◽

Stem Cell ◽

Cell Population ◽

Side Population ◽

Chemotherapeutic Agents ◽

Stem Cell Population ◽

Exact Function

As an important member of the Argonaute protein family, PIWI-like protein 1 (PIWIL1) plays a key role in tumor cell viability. However, the exact function of PIWIL1 in multiple myeloma (MM) and the underlying mechanism remain unclear. Here, we revealed that PIWIL1 was highly expressed in myeloma cell lines and newly diagnosed MM patients, and that its expression was notably higher in refractory/relapsed MM patients. PIWIL1 promoted the proliferation of MM cells and conferred resistance to chemotherapeutic agents both in vitro and in vivo. More importantly, PIWIL1 enhanced the formation of autophagosomes, especially mitophagosomes, by disrupting mitochondrial calcium signaling and modulating mitophagy-related canonical PINK1/Parkin pathway protein components. Mitophagy/autophagy inhibitors overcome PIWIL1-induced chemoresistance. In addition, PIWIL1 overexpression increased the proportion of side population (SP) cells and upregulated the expression of the stem cell-associated genes Nanog, OCT4, and SOX2, while its inhibition resulted in opposite effects. Taken together, our findings demonstrated that PIWIL1 induced drug resistance by activating mitophagy and regulating the MM stem cell population. PIWIL1 depletion significantly overcame drug resistance and could be used as a novel therapeutic target for reversing resistance in MM patients.

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Identification and characterization of a transient outward K+ current in human induced pluripotent stem cell-derived cardiomyocytes

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2013.03.014 ◽

2013 ◽

Vol 60 ◽

pp. 36-46 ◽

Cited By ~ 39

Author(s):

Jonathan M. Cordeiro ◽

Vladislav V. Nesterenko ◽

Serge Sicouri ◽

Robert J. Goodrow ◽

Jacqueline A. Treat ◽

...

Keyword(s):

Stem Cell ◽

Pluripotent Stem Cell ◽

Induced Pluripotent Stem Cell ◽

K Current ◽

Induced Pluripotent ◽

Identification And Characterization

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What is the future of immunotherapy in multiple myeloma?

Blood ◽

10.1182/blood.2019004176 ◽

2020 ◽

Vol 136 (22) ◽

pp. 2491-2497

Author(s):

Leo Rasche ◽

Michael Hudecek ◽

Hermann Einsele

Keyword(s):

Multiple Myeloma ◽

Monoclonal Antibodies ◽

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Cell Therapies ◽

The Future

Abstract The treatment of multiple myeloma (MM) is currently being redefined by humoral and cellular immunotherapies. For decades, there was limited belief in immune-based anti-MM therapy as a result of the moderate graft-versus-myeloma effect of allogeneic stem cell transplantation. Today, monoclonal antibodies comprise the new backbone of anti-MM therapy, and T-cell therapies targeting BCMA are emerging as the most potent single agents for MM treatment. Herein, we present our assessment of and vision for MM immunotherapy in the short and midterm.

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Identification and characterization of inhibitors of G protein-coupled receptor kinase 6 (GRK6) as potential therapeutics for multiple myeloma

Qatar Foundation Annual Research Forum Proceedings ◽

10.5339/qfarf.2012.aesnp12 ◽

2012 ◽

pp. AESNP12 ◽

Cited By ~ 1

Author(s):

Rima Al-awar ◽

David Uehling ◽

Babu Joseph ◽

Carly Griffin ◽

Ratheesh Subramaniam ◽

...

Keyword(s):

Multiple Myeloma ◽

G Protein ◽

Receptor Kinase ◽

G Protein Coupled Receptor ◽

G Protein Coupled ◽

Identification And Characterization ◽

Potential Therapeutics

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Bortezomib Therapy for Multiple Myeloma in Relapse after Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation (RICT).

Blood ◽

10.1182/blood.v106.11.5399.5399 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5399-5399

Author(s):

Sophie Ducastelle ◽

Daniela Revesz ◽

Jacques Troncy ◽

Samira Mahmoudi ◽

Xavier Thomas ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Median Time ◽

New Drugs ◽

Hematological Toxicity ◽

Hematopoietic Stem

Abstract Multiple myeloma (MM) remains incurable and specially of poor prognosis in case of refractory or relapsed disease. However, recent therapeutic advances including the use of new drugs are promising. Although, Bortezomib, new proteasome inhibitor, has proven its efficacy in patients with refractory or relapsed MM, it has not been sufficiently evaluated in the setting of allogeneic hematopoietic stem cell transplantation. Here, we report four cases of MM patients, very heavily pre-treated and all previously transplanted, who received bortezomib associated to dexamethasone for relapse after allogeneic RICT (median time from diagnosis: 68 months, median time from RICT: 41 months). We studied the feasibility, efficacy and safety of bortezomib: two patients achieved a complete remission, one patient a very good partial response, and one had no response. The tolerance was excellent with only one patient who developed a reversible grade 3 hematological toxicity. No GVHD recrudescence was observed. All patients relapsed after completion of bortezomib treatment. This questions about the potential benefit of maintenance therapy with bortezomib. Given the feasibility and the high efficacy of bortezomib combined with dexamethasone in relapsed MM after RICT, our results argue in favour of an immune-modulatory activity of bortezomib. New strategies combining RICT and bortezomib are warranted to increase and maintain an adequate response. Combination RICT and bortezomib regimen are anticipated to further extend survival in relapsed MM.

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