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Cited by 22Multiple Myeloma Research and TreatmentsEpigenetics and DNA MethylationAcute Myeloid Leukemia Research

The Role of Epigenetics in the Development and Progression of Multiple Myeloma

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Ismail, Nor Hayati, Mussa, Ali, Zakaria, Nur Atikah, Al-Khreisat, Mutaz Jamal, Zahidin, Muhamad Aidil, Ramli, Noor Nabila, Mohammad, Siti Nur Nabeela A’ifah, Hassan, Rosline +6 more·2022·Biomedicines
DOI 10.3390/biomedicines10112767PMC PMC9687797
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Abstract

Multiple myeloma (MM) is an exceptionally complicated and heterogeneous disease that is caused by the abnormal proliferation of malignant monoclonal plasma cells initiated in the bone marrow. In disease progression, a multistep process including differentiation, proliferation, and invasion is involved. Despite great improvement in treatment outcomes in recent years due to the substantial discovery of novel therapeutic drugs, MM is still regarded as an incurable disease. Patients with MM are afflicted by confronting remission periods accompanied by relapse or progression outcomes, which inevitably progress to the refractory stage. In this regard, MM may need new medications or modifications in therapeutic strategies to overcome resistance. A variety of genetic abnormalities (e.g., point mutations, translocations, and deletions) and epigenetic changes (e.g., DNA methylation, histone modification, and non-coding RNA) contribute to the pathogenesis and development of MM. Here, we review the significant roles of epigenetic mechanisms in the development and progression of MM. We also highlight epigenetic pathways as potential novel treatment avenues for MM, including their interplay, use of epigenetic inhibitors, and major involvement in immuno-oncology.

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  • The HOX family has been identified as the primary driver of osteoblast differentiation.

    “According to this perspective, the primary driver of osteoblast differentiation has been identified as the HOX family [142].”

    From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [142]

  • Approximately 80% of MM patients exhibit elevated levels of NF-κB p65 subunits in bone marrow samples.

    “Approximately 80% of MM patients exhibit elevated levels of NF-κB p65 subunits in bone marrow samples [60, 61, 138, 139].”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [139]

    The passages from Section 4 (DNA Methylation) and Section 8 (Epigenetic Effects on Immunomodulation) discuss other molecular changes in multiple myeloma, not NF-κB p65 levels. Further searches for NF-κB, p65, and the 80% figure found no passage reporting elevated p65 in bone marrow samples from approximately 80% of patients. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

  • Aberrant activation of NF-κB signaling is crucial in MM pathogenesis.

    “The aberrant activation of NF-κB signaling is crucial in MM pathogenesis.”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [139]

    Section 8 discusses activation of IL-6/JAK/STAT3 and Wnt signaling in multiple myeloma, but neither passage addresses NF-κB. Searches for NF-κB and NF-kB activation found no passage in our copy stating its role in MM pathogenesis. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Ismail, N. H., Mussa, A., Zakaria, N. A., Al-Khreisat, M. J., Zahidin, M. A., Ramli, N. N., Mohammad, S. N. N. A., Hassan, R., Mohd Noor, N. H., Iberahim, S., Zulkafli, Z., Mohamed Yusoff, S., Husin, A., & Johan, M. F.
Affiliations
  • Universiti Sains Malaysia (MY)
  • Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
Corresponding author
Johan, Muhammad Farid
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2022-10-31
Volume
10
Issue
11
Pages
2767
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines10112767
PMC
PMC9687797
OpenAlex
W4308124850
Cited by
22
References
10
Citations by year
2026: 6 · 2025: 4 · 2024: 5 · 2023: 7
FWCI
0.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
GIPS-PhD (311/PPSP/4404822)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords
multiple myeloma, epigenetics, DNA methylation, histone modifications, non-coding RNA, disease progression, relapse, refractory multiple myeloma, epigenetic inhibitors, cancer immunotherapy, plasma cell proliferation, genetic abnormalities

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