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Myeloma Stem Cells- Unraveling the Enigma of Cancer’s Persistence

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Myeloma is an incurable cancer. A reasonable percentage of MM patients achieve minimal residual disease (MRD) from their induction or ASCT. This means that chemotherapy and radiation can kill myeloma cancer cells until there are only 4 MM cells for every one million good cells.

But our MM comes back again and again. How can this happen? Understanding myeloma stem cells may be the reason.

Defining Myeloma Stem Cells

Myeloma stem cells are a rare subpopulation of cells within the tumor microenvironment of multiple myeloma. Unlike the bulk of myeloma cells, which have a limited lifespan, MMSCs possess self-renewal capacity, enabling them to generate identical copies of themselves and maintain a pool of undifferentiated cells. This characteristic, akin to normal stem cells, allows MMSCs to persist over time, evade traditional treatments, and contribute to disease relapse.

Origins and Characteristics of MMSCs

The precise origin of MMSCs remains a subject of ongoing research. Some studies suggest that MMSCs may arise from either a transformed precursor cell within the bone marrow or from dedifferentiation of mature myeloma cells. Regardless of their exact origin, MMSCs share several key features that distinguish them from differentiated myeloma cells. These features include enhanced drug resistance, increased tumorigenic potential, and the ability to modulate the tumor microenvironment to favor their survival.

Role in Disease Progression

MMSCs play a pivotal role in driving the progression and recurrence of multiple myeloma. Through their self-renewal capacity, MMSCs replenish the pool of cancer cells even after aggressive therapeutic interventions. Moreover, their enhanced drug resistance makes them impervious to conventional treatments, allowing them to serve as a source of repopulation for the tumor. This resilience poses a significant clinical challenge, as it necessitates the development of targeted therapies specifically designed to eradicate MMSCs.

Challenges in Targeting MMSCs

Developing effective therapies against MMSCs is a complex endeavor, primarily due to their elusive nature and the heterogeneity within the myeloma stem cell population. Traditional treatments, which often target rapidly dividing cells, may not effectively eliminate MMSCs due to their relatively quiescent state. Additionally, the dynamic interplay between MMSCs and the surrounding microenvironment further complicates efforts to target them.

Emerging Therapeutic Strategies

Despite the challenges, significant progress has been made in understanding the biology of MMSCs and developing novel therapeutic approaches. Recent studies have explored various strategies, including targeting specific signaling pathways, immunotherapies, and epigenetic modifications, to selectively eradicate MMSCs while sparing normal cells. Additionally, advances in single-cell sequencing technologies are providing invaluable insights into the heterogeneity of MMSC populations, offering potential avenues for precision medicine approaches.


Myeloma stem cells represent a critical aspect of multiple myeloma biology, driving disease progression and contributing to therapeutic resistance. Understanding their unique properties and developing targeted therapies against them is crucial in improving outcomes for patients with multiple myeloma. As research continues to unravel the intricacies of MMSC biology, the prospect of more effective and personalized treatments holds promise for transforming the landscape of multiple myeloma management.

Read the posts linked below to learn more about cancer stem cells-

To date, the only therapy that I know of that can kill myeloma stem cells is hyperthermia. Interestingly, this therapy enhances the efficacy of velcade aka bortezomib. 

Have you been diagnosed with multiple myeloma? Let me know- David.PeopleBeatingCancer@gmail.com


David Emerson

  • MM Survivor
  • MM Cancer Coach
  • Director PeopleBeatingCancer

Cell-of-Origin of Cancer versus Cancer Stem Cells: Assays and Interpretations

Cancer-initiating cell, or the cell-of-origin of cancer, is the normal cell that receives the first cancer-causing mutations. In other words, the cancer-initiating cell founds a future clinical tumor. Cancer stem cells (CSCs), on the other hand, are the cells that maintain tumor propagation ().

The myeloma stem cell concept, revisited: from phenomenology to operational terms

“The multiple myeloma stem cell (MMSC) is defined as a cell within the malignant tissue that possesses the capacity to self-renew and to differentiate into the predominant lineages of myeloma plasma cells comprising the neoplasm…

The stem-cell concept and the B-cell hierarchy

A normal stem cell is a unique cell type present at low frequency which can renew itself and produce progenitors of one or more specialized cell types. Beginning with the fertilized oocyte, cellular differentiation into specialized cell types, tissues, and organs follows a strict pattern…

Stem cells may be classified into two major classes:

  1. pluripotent stem cells derived from early embryos that are able to replenish all cell types in the human body, and
  2. multipotent stem cells located in various organs that are dedicated to the replenishment of specific tissues such as blood…

Targeting Multiple Myeloma Cancer Stem Cells with Natural Products – Lessons from Other Hematological Malignancies

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