Multiple Myeloma: Molecular Pathogenesis and Disease Evolution

Heider, Michael; Nickel, Katharina; Högner, Marion; Bassermann, Florian

doi:10.1159/000520312

Cited by 42 publications

(31 citation statements)

References 101 publications

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“…We first analyzed CD levels during the different stages of disease evolution and found CD24 to be weakly expressed during the MGUS/SMM stages but up-regulated in the relapsed/resistant stages of disease. Consistent with the claim that CD24 plays a major role in solid tumor metastasis [ 33 ], this suggests that MM may lose its stromal dependence as the disease evolves [ 34 , 35 ].…”

Section: Discussionsupporting

confidence: 79%

CD24 Is a Prognostic Marker for Multiple Myeloma Progression and Survival

Even‐Zohar

Pick

Hofstetter

et al. 2022

JCM

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Surface antigens are commonly used in flow cytometry assays for the diagnosis of multiple myeloma (MM). Some of these are directly involved in MM pathogenesis or interactions with the microenvironment, but most are used for either diagnostic or prognostic purposes. In a previous study, we showed that in-vitro, CD24-positive plasma cells exhibit a less tumorigenic phenotype. Here, we assessed the prognostic importance of CD24 expression in patients newly diagnosed with MM as it correlates to their clinical course. Immunophenotyping by flow cytometry of 124 patients uniformly treated by a bortezomib-based protocol was performed. The expression of CD24, CD117, CD19, CD45, and CD56 in bone marrow PCs was tested for correlations to clinical parameters. None of the CD markers correlated with the response rates to first-line therapy. However, patients with elevated CD24+ expression on their PCs at diagnosis had a significantly longer PFS (p = 0.002) and OS (p = 0.044). In contrast, the expression of CD117, CD56, or CD45 was found to have no prognostic value; CD19 expression was inversely correlated with PFS alone (p ˂ 0.001) and not with OS. Thus, elevated CD24 expression on PCs appears to be strongly correlated with survival and can be used as a single-surface antigenic prognostic factor in MM.

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Section: Discussionsupporting

confidence: 79%

CD24 Is a Prognostic Marker for Multiple Myeloma Progression and Survival

Even‐Zohar

Pick

Hofstetter

et al. 2022

JCM

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“…Multiple myeloma (MM), which arises from the uncontrolled proliferation of malignant plasma cells, is the second most common hematological malignancy (1). The overall survival (OS) of MM patients has been significantly increased due to the availability of drugs such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies, and transplantation of autologous stem cells (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor in Multiple Myeloma

Chen

Gao

et al. 2022

Front. Oncol.

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Inositol polyphosphate-4-phosphatase type II (INPP4B) has been identified as a tumor suppressor, while little is known about its expression and function in multiple myeloma (MM). In this study, we evaluated the expression of INPP4B in 28 cases of newly diagnosed MM patients and 42 cases of extramedullary plasmacytoma (EMP) patients compared with normal plasma cells and found that low INPP4B expression was correlated with poor outcomes in MM patients. Moreover, expression of INPP4B in seven MM cell lines was all lower than that in normal plasma cells. In addition, loss of function of INPP4B promoted cell proliferation in MM cells; however, gain of function suppressed MM cells proliferation and arrested the cell cycle at G0/G1 phage. Meanwhile, knockdown of INPP4B enhanced resistance, but overexpression promoted sensitivity to bortezomib treatment in MM cells. Mechanistically, we found that INPP4B exerted its role via inhibiting the phosphorylation of Akt at lysine 473 but not threonine 308, which attenuated the activation of the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Therefore, we identified an inhibitory effect of INPP4B in MM, and our findings suggested that loss of INPP4B expression is a risk factor of aggressive MM.

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“…Multiple myeloma is a neoplastic disorder of plasma cells, which accounts for 10% of hematological malignancies, making it the second most common hematological malignancy. Risk factors for this malignancy are yet to be identified, but its incidence is higher in males and African ethnicity [ 8 - 10 ]. One of the most common presentations of this malignancy is back pain, which occurs in up to 58% of patients.…”

Section: Discussionmentioning

confidence: 99%

Surgical Intervention for Spinal Lesions Due to Multiple Myeloma: A Case Report

Almetrek¹,

Mahjari²,

Aldharman³

et al. 2023

Cureus

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Vertebral disease is a main source of morbidity (MM) in individuals with multiple myeloma. The effects of associated osteolytic lesions and vertebral fractures on severe pain, functional limits, spinal deformity, and cord compression are well recognized. Systemic therapy, radiation, cementoplasty (vertebroplasty/kyphoplasty), and radiofrequency ablation are now available therapeutic options for severe MM spinal pain. We here reported a case of a 45-year-old male who had complained of progressive symptoms of pathological spine fractures. He had been examined and investigated for the cause of lytic lesions and found to have multiple fractures in the spine. A computed tomography (CT) revealed multiple osteolytic lesions noted in the thoracolumbar spine, ribs (bilaterally), and pelvic bones. Magnetic resonance imaging (MRI) showed a compression fracture of the T8 vertebral body with evidence of retro-bulging and a spinal canal narrowing. However, there was no evidence of spinal cord abnormal signal intensity. T2 weighted image (T2WI) keeping with edema is noted. A surgical intervention fixed the fracture and improved the quality of life. Vertebroplasty, a minimally invasive procedure, as a treatment option for vertebral lesions and pathologic fractures in the MM, showed good clinical improvement in the patient.

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Multiple Myeloma: Molecular Pathogenesis and Disease Evolution

Cited by 42 publications

References 101 publications

CD24 Is a Prognostic Marker for Multiple Myeloma Progression and Survival

CD24 Is a Prognostic Marker for Multiple Myeloma Progression and Survival

Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor in Multiple Myeloma

Surgical Intervention for Spinal Lesions Due to Multiple Myeloma: A Case Report

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