Special Issue "New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple Myeloma"

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: 15 May 2023 | Viewed by 3165

Special Issue Editors

Hematology Section of the 1st Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens’ Medical School, Laikon Hospital, 11527 Athens, Greece
Interests: multiple myeloma; Waldenstrom's macroglobulinemia; lymphomas; leukemias; myeloproliferative disorders; myelodysplastic syndromes; prognosis; microenvironment; cytokines
Department of Therapeutics, National and Kapodistrian University of Athens’ Medical School, Alexandras Hospital, Athens, Greece
Interests: multiple myeloma; Waldenstrom’s macroglobulinemia; amyloidosis; lymphomas; oncology
Department of Internal Medicine, Alexandroupolis University Hospital, Democritus University of Thrace’s Medical School, Alexandroupolis, Greece
Interests: multiple myeloma; Waldenstrom’s macroglobulinemia; amyloidosis; lymphomas; oncology

Special Issue Information

Dear Colleagues,

Multiple myeloma (MM) is a plasmacytic dyscrasia characterized by monoclonal paraprotein-secreting plasma cells, proliferating in the bone marrow, and accompanied by morbid manifestations such as bone pains with eventual spontaneous fractures, anemia, renal failure, possible hypercalcemia, and frequent febrile infection. The disease course is punctuated by remissions followed by relapses.

Increasing knowledge about myeloma underlining biology along with technology improvements have led to an unbelievable treatment evolution for the benefit of most patients. Likewise, with the introduction of proteasome inhibitors and IMiDs that became the basis of most therapeutic schemas, coupled with monoclonal antibodies and other new agents, the duration of responses and overall survival have been substantially prolonged, and the quality of life improved. Meanwhile, newer modalities are emerging, and some are already available, allowing the most promising ones to potentially cure for some of our patients.

Over recent years, diagnostic procedures and risk stratification strategies have adapted to the new state of management and have been improved. However, due to the emergence of aggressive myeloma sub-clones and unknown biologic processes, the disease ultimately escapes treatment control and becomes lethal. Therefore, a lot remains to be studied, evaluated, and assessed in order to reach optimal effect.

We would like to invite physicians and researchers involved in this field to contribute to this Special Issue with their observations and results.

Prof. Dr. Marie-Christine Kyrtsonis
Prof. Dr. Meletios-Athanasios Dimopoulos
Dr. Emmanouil Spanoudakis
Guest Editors

Manuscript Submission Information

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Keywords

  • multiple myeloma
  • diagnosis procedures
  • prognosis
  • treatment
  • biology
  • prognostic factors
  • pathophysiology

Published Papers (3 papers)

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Research

Article
Inhibition of Sphingosine Kinase 2 Results in PARK2-Mediated Mitophagy and Induces Apoptosis in Multiple Myeloma
Curr. Oncol. 2023, 30(3), 3047-3063; https://doi.org/10.3390/curroncol30030231 - 04 Mar 2023
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Abstract
Mitophagy plays an important role in maintaining mitochondrial homeostasis by clearing damaged mitochondria. Sphingosine kinase 2 (SK2), a type of sphingosine kinase, is an important metabolic enzyme involved in generating sphingosine-1-phosphate. Its expression level is elevated in many cancers and is associated with [...] Read more.
Mitophagy plays an important role in maintaining mitochondrial homeostasis by clearing damaged mitochondria. Sphingosine kinase 2 (SK2), a type of sphingosine kinase, is an important metabolic enzyme involved in generating sphingosine-1-phosphate. Its expression level is elevated in many cancers and is associated with poor clinical outcomes. However, the relationship between SK2 and mitochondrial dysfunction remains unclear. We found that the genetic downregulation of SK2 or treatment with ABC294640, a specific inhibitor of SK2, induced mitophagy and apoptosis in multiple myeloma cell lines. We showed that mitophagy correlates with apoptosis induction and likely occurs through the SET/PP2AC/PARK2 pathway, where inhibiting PP2AC activity may rescue this process. Furthermore, we found that PP2AC and PARK2 form a complex, suggesting that they might regulate mitophagy through protein–protein interactions. Our study demonstrates the important role of SK2 in regulating mitophagy and provides new insights into the mechanism of mitophagy in multiple myeloma. Full article
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Article
Assessing Pretransplant and Posttransplant Therapy Response in Multiple Myeloma Patients
Curr. Oncol. 2022, 29(11), 8501-8512; https://doi.org/10.3390/curroncol29110670 - 08 Nov 2022
Viewed by 1023
Abstract
Multiple myeloma (MM) is a hematologic cancer defined by an abnormal development of clonal plasma cells in the bone marrow, releasing vast quantities of immunoglobulins and different proteins. In the majority of patients, MM remains incurable despite decades of medical improvement and a [...] Read more.
Multiple myeloma (MM) is a hematologic cancer defined by an abnormal development of clonal plasma cells in the bone marrow, releasing vast quantities of immunoglobulins and different proteins. In the majority of patients, MM remains incurable despite decades of medical improvement and a number of treatment breakthroughs. Frontline standard-of-care has little long-term success, with the majority of patients eventually relapsing, although the overall progression-free survival (PFS) has improved significantly in the last ten years. Patients who are eligible for a transplant have the highest PFS rate at 5 years, depending on medication response and other various factors that are yet to be discovered. Therefore, the current study aimed to evaluate the response to VCD (bortezomib, cyclophosphamide, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) used as pretransplant regimens, as well as to compare responses between thalidomide and lenalidomide used as maintenance therapy posttransplant. This retrospective study was performed on a group of 105 hospitalized patients in the Hematology Department of the Timisoara Municipal Emergency Clinical Hospital between January 2016 and December 2021. Data was collected from the paper records of patients with MM who were under-followed. The treatment regimens used as induction therapy were either VCD or VTD if cyclophosphamide was contraindicated. Of the 105 patients, 27 became eligible for bone marrow transplantation. Furthermore, they received maintenance therapy which was based on either lenalidomide with dexamethasone or thalidomide with dexamethasone. Of the 62 patients treated with VTD, 17.7% were in complete remission before stem cell transplantation. Of the 43 patients treated with VCD, 37.2% were in complete remission. The 5-year mean progression-free survival (PFS) in the entire cohort was better in the group treated with the VTD regimen (31.6 vs. 27.2 months). However, in the 27 patients undergoing maintenance after ASCT, the PFS with thalidomide was 35.5 months (95% CI = 27–42), while the PFS rate in those receiving maintenance treatment with lenalidomide was 46.1 months (95% CI = 20–73). VCD proved to be superior to VTD in inducing complete pretransplant responses. Regarding maintenance therapy, patients from the lenalidomide group had superior responses compared with those under thalidomide. Full article
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Article
Spinal Lesions as Clinical Manifestations of Plasma Cell Neoplasia
Curr. Oncol. 2022, 29(9), 6236-6244; https://doi.org/10.3390/curroncol29090490 - 29 Aug 2022
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Abstract
(1) Background: Plasma cell neoplasia can be separated into independent subtypes including multiple myeloma (MM) and solitary plasmacytoma of the bone (SBP). The first clinical signs patients present with are skeletal pain, most commonly involving ribs and vertebrae. (2) Methods: Retrospective analysis of [...] Read more.
(1) Background: Plasma cell neoplasia can be separated into independent subtypes including multiple myeloma (MM) and solitary plasmacytoma of the bone (SBP). The first clinical signs patients present with are skeletal pain, most commonly involving ribs and vertebrae. (2) Methods: Retrospective analysis of 114 patients (38 female, 76 male) receiving spinal surgery from March 2006 until April 2020. Neurological impairments and surgical instability were the criteria for intervention in this cohort. Analysis was based on demographic data, Spinal Instability Neoplastic Score (SINS), location of the lesion, spinal levels of tumor involvement, surgical treatment, histopathological workup, adjuvant therapy, functional outcome, and overall survival (OS). (3) Results: The following surgical procedures were performed: posterior stabilization only in 9 patients, posterior stabilization and decompression without vertebral body replacement in 56 patients, tumor debulking and decompression only in 8 patients, anterior approach in combined approach without vertebral body replacement and without biopsy and/or without kyphoplasty in 33 patients, 3 patients received biopsies only, and 5 patients received kyphoplasty only. The histopathology diagnoses were MM in 94 cases and SBP in 20 cases. Median OS was 72 months (53.4–90.6 months). Preoperative KPSS was 80% (range 40–100%), the postoperative KPSS was 80% (range 50–100%). (4) Conclusions: Surgery for patients with plasma cell neoplasia is beneficial in case of neurological impairment and spinal instability. Moreover, we were able to show that patients with MM and a low number of spinal levels to be supplied have a better prognosis as well as a younger age at the time of the surgical intervention. Full article
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