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At least 19 recordsLinked to original sources
PubMed1979

[New aspects in the clinical course determination and therapy in multiple myeloma].

Multiple myeloma can be regarded as model disease for quantification of tumor mass, investigation of tumor cell kinetics and of tumor response to therapy. The quantification of the tumor cell number allows evaluation of prognosis and monitoring of disease as well as of therapy induced responses. Treatment of multiple myeloma is primarily based on the alkylating drugs cyclophosphamide and melphalan. In recent years other cytostatic substances, also effective in the treatment of this disorder have been introduced. However, the sensitivity determination of the individual myeloma stem cells seems to be the only possible method which possibly increases the response rate significantly. In accordance with these considerations we have, in preliminary clinical investigations, observed a good correlation between the in vitro determined cytostatic drug sensitivity and the in vivo response to therapy. Further progress in the treatment of multiple myeloma is to be expected with the introduction of interferon into the therapeutic regimen. Administration of this glycoprotein has resulted in significant reduction of tumor mass in more than half of all patients treated up to this time.

Antineoplastic Agents↗
PubMed2026

Comprehensive Analyses of SOX7 Provide Novel Insights on Its Tumor Suppressor Role and Its Target Genes with Therapeutic Implications in Multiple Myeloma.

Multiple myeloma (MM) is an incurable hematological malignancy. SOX7, located within the recurrently deleted 8p23.1 region in MM, is suggested to act as a tumor suppressor. We characterized SOX7 through genetic, epigenetic, and functional analyses in MM cell lines. SOX7 was frequently silenced due to deletion and/or promoter hypermethylation. Ectopic SOX7 expression in KMS-18 and MM.1S cell lines caused a progressive decline in SOX7-transduced cells and induced G1 cell cycle arrest and/or apoptosis. Although SOX7 re-expression did not enhance bortezomib efficacy, treatment with the pan-histone deacetylase inhibitor panobinostat induced G1 arrest, promoted apoptosis, and increased SOX7 expression in MM.1S cells. Whole-transcriptome sequencing identified G1/S progression-related Wnt/β-catenin pathway genes as major SOX7-regulated targets, while ChIP-Seq analysis revealed widespread genomic SOX7 occupancy in MM.1S. Flow cytometric analysis of permeabilized bone marrow tumor cells from newly diagnosed and relapsed MM patients demonstrated generally low SOX7 protein expression. Collectively, these results indicate that SOX7 functions as a tumor suppressor in MM, and its inactivation promotes cell cycle progression. The anti-myeloma effects of panobinostat in MM.1S cells may be partially mediated through SOX7 induction.

Multiple Myeloma↗
PubMed1977

Unusual presentations of multiple myeloma.

Multiple myeloma has many unusual manifestations, which may obscure the true cause and delay proper treatment. Physicians in all specialties should be alert to this possibility, since myeloma may be at the root of such diverse disorders as carpal tunnel syndrome, peripheral neuropathy, solitary lytic bone lesions, hypercalcemia, and hyperviscosity syndrome.

Adult↗
PubMed1976

Neutrophil defect in multiple myeloma. Studies on intraneutrophilic lysozyme in multiple myeloma and malignant lymphoma.

Intracellular lysozyme concentration was measured in neutrophilic granulocytes from 25 patients with multiple myeloma. At diagnosis intraneutrophil lysozyme activity was significantly reduced (mean reduction 50%). During clinical remission after 1-4 months of intensive chemotherapy values were normalized. In 18 cases studied at various stages of the disease from 6 to 70 months after diagnosis there was a significant negative correlation between the duration of the disease and neutrophil lysozyme concentration. The decrease in neutrophil lysozyme concentration was significantly correlated to clinical disease activity and the percentage of plasma cells in bone marrow aspirates, whereas there was no correlation between the concentration of M-protein in serum and the neutrophil lysozyme concentration. Plasma lysozyme concentration was normal. In contrast, neutrophil lysozyme concentration was normal in 18 patients with stage III-IV malignant lymphoma. Plasma lysozyme in this group was significantly higher than normal. The difference in neutrophil lysozyme patterns between multiple myeloma and malignant lymphoma supports the hypothesis that the defect in neutrophil maturation seen in malignant blood disorders is directly related to the infiltration of the bone marrow by pathologic cells.

Antineoplastic Agents↗
PubMed2026

Integrated Genomic and Epigenomic Analysis Reveals Epigenetic Plasticity in Disease Progression and Multidrug Resistance in Multiple Myeloma.

UNLABELLED: Multiple myeloma is marked by recurrent cytogenetic abnormalities and mutations that accumulate as the disease progresses. In this study, we sought to elucidate the transitions driving tumorigenesis and therapy resistance in multiple myeloma using a unique cohort of nearly 900 patients spanning premalignant to late-stage refractory multiple myeloma, comprehensively characterized at molecular and clinical levels. Waves of epigenetic dysregulation drove these critical transitions. In this paradigm, genomic and cytogenetic events unlocked epigenetic plasticity, reshaping multiple myeloma cell biology to evade tumor microenvironment constraints and therapeutic pressures. Functional perturbation studies in an isogenic proteasome inhibitor-resistant cell line model demonstrated enhanced reliance on transcriptional cofactors, supporting a mechanistic link between chromatin plasticity and therapy adaptation. Collectively, these findings support a unifying framework in which genomic heterogeneity unlocks gene regulatory plasticity, enabling plasma cells (PC) to evade microenvironmental constraints and therapeutic pressure. These results provide a mechanistic explanation for sequential relapse without new genomic alterations and nominate epigenetic plasticity-mediated PC adaptation as a therapeutic vulnerability in the heterogeneous genetic background of multiple myeloma. SIGNIFICANCE: Assembly and analysis of a multiple myeloma cohort spanning the continuum from premalignant to late relapse that integrates bulk transcriptomics with single-cell multiomic data provides insights into disease progression and epigenetic plasticity.

Multiple Myeloma↗
PubMed2026

Independent prognostic value of semaphorin-4D, interleukin-1β and complement activation in newly diagnosed multiple myeloma patients.

Multiple myeloma represents a systemic disease of the bone marrow (BM) niche, in which immune and skeletal pathways are tightly interconnected. However, the independent prognostic significance of bone and immune-related markers in newly diagnosed multiple myeloma (NDMM) remains incompletely understood. Semaphorin (Sema) 4D, activin-A, and periostin ELISA, LEGENDplex™ Human Bone Metabolism Panel and proteomic analysis for novel biomarker identification were conducted in 71 consecutive samples from NDMM patients. In 25 patients, genomic analysis was performed on sorted clonal plasma cells. NDMM patients had a median age at diagnosis of 65 years and a median follow-up of 2.5 years. Interleukin (IL)-1β and Sema4D levels predicted progression-free survival (PFS), highlighting their role in disease relapse. Proteomic profiling revealed a systemic signature associated with worse prognosis, enriched in complement activation components. Complement C5 significantly affected PFS and time to progression (TTP). IL-1β and C5 predicted PFS independently of the second revision of the International Staging System (R2-ISS) stage, and a similar trend was noted for Sema4D. Myeloma bone disease (MBD) did not significantly affect overall survival, PFS, or TTP, suggesting that contemporary treatments mitigate its impact. Genomic analyses identified variants associated with inferior PFS, including HLA-DRB5 (c.300_306delinsCGGG) and HLA-DQB1 (c.317_319delinsCGG). Sema4D and the IL-1β-complement cascade emerged as key drivers of disease progression, independent of R2-ISS stage, representing potential prognostic and therapeutic targets in NDMM.

Journal Article↗
PubMed2026

PPRC1 is a prognostic biomarker and key regulator of mitochondrial oxidative phosphorylation in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) remains an incurable haematological malignancy, underscoring the need for novel prognostic biomarkers and therapeutic targets. This study aimed to investigate the clinical and biological significance of peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1) in MM. METHODS: Expression and clinical data were obtained from public databases and an independent local cohort. Kaplan-Meier and Cox regression analyses were performed to evaluate prognostic value. Differential expression analysis, pathway enrichment analysis and single-cell RNA-seq data analysis were used to explore biological functions. PPRC1 was silenced in MM cell lines using siRNA to assess its effects on cell survival and oxidative phosphorylation. RESULTS: PPRC1 was significantly upregulated in MM and was associated with advanced disease stage and poor overall survival. Multivariate Cox analysis identified PPRC1 as an independent prognostic factor. A nomogram incorporating PPRC1 and revised-ISS improved survival prediction. Functional analyses revealed that PPRC1 was positively correlated with oxidative phosphorylation and oncogenic signalling pathways. A potential connection between PPRC1 expression and immune cell infiltration was observed. PPRC1 knockdown inhibited cell proliferation, induced cell cycle arrest and apoptosis and impaired oxidative phosphorylation in MM. CONCLUSIONS: PPRC1 acts as a prognostic biomarker and metabolic regulator in MM by sustaining mitochondrial oxidative phosphorylation. These findings highlight PPRC1 as a potential therapeutic target in MM.

Humans↗
PubMed1977

Combined calcitonin and oral phosphate treatment for hypercalcemia in multiple myeloma.

Hypercalcemia of multiple myeloma has been discussed widely in the medical literature. The role of calcitonin and phosphate in the treatment of hypercalcemia of multiple myeloma has not yet been studied to our knowledge, although experimental animal models have been pointing to the role of phosphate supplement to calcitonin treatment in multiple myeloma. A patient had multiple myeloma and hypercalcemia. The usual medical treatment for hypercalcemia failed; however, the treatment with combined orally administered phosphate and calcitonin was successful. The role of phosphate depletion in this setting is brought up as an important factor in the failure of calcitonin therapy.

Calcitonin↗
PubMed1976

Mutations in mouse myeloma cells: implications for human multiple myeloma and the production of immunoglobulins.

Multiple myeloma raises a number of puzzling questions about the production of immunoglobulins and the malignant transformation of lymphoid cells. Some of these questions can be approached by studying mouse plasmacytomas and by genetic and biochemical studies of mouse myeloma cells in culture. The synthesis, assembly, glycosylation, and secretion of immunoglobulin has been analyzed in detail using the mouse myeloma system. The development of a technique that detects variants in clones of cultured mouse myeloma cells has led to the demonstration of a unique genetic instability in these cells. Based on these results a model is presented to explain the high frequency of ligh-chain producing (Bence Jones) myelomas in patients. Finally, mutant cell lines have been recovered which produce defective immunoglobulins similar to those found in heavy-chain disease and some other lymphoproliferative disorders.

Amino Acid Sequence↗
PubMed1977

Second malignancies in patients with multiple myeloma.

Seven patients with multiple myeloma who developed a second neoplasm are presented. There were four patients with acute leukemia and three patients with non-hematologic neoplasms. The patients with acute leukemia were among the longest survivors (median duration approximately 72 months) and the response to anti-leukemic therapy in these patients was generally poor. Of the three patients with non=hematologic neoplasms, one patient was observed with simultaneous renal cell carcinoma and the other two patients developed adenocarcinoma of the colon and lung subsequently. In addition, two patients with mammary carcinoma who subsequently developed multiple myeloma were included. Literature was reviewed and the possibility that multiple myeloma itself might be a risk factor for the development of other malignancies was discussed.

Adenocarcinoma↗
PubMed1977

[Autopsy-statistical analysis of multiple myeloma (author's transl)].

150 autopsies with multiple meyeloma were analysed. In about one third of the cases the multiple myeloma was diagnosed only at autopsy. Two thirds of the carriers of multiple myeloma were between 60 and 70 years old when they deceased. The osseous foci of multiple myeloma extended predominantly to the central parts of the skeletal system. In 120 patients the multiple myeloma was the cause of death. In half of these cases infections, particularly of the lung, had caused death. The second frequent cause of death was uraemia. 63 of the 150 multiple myeloma have been immunologically classified. The cases in question are 10 IgA-, 2 IgD-, and 42 IgG-multiple myeloma. Extraosseous foci of multiple myeloma appeared significantly more frequent in IgA-than in IgG-multiple myeloma. A haemorrhagic diathesis existed more frequent in IgA-multiple myeloma. Venous thromboses were more frequently to be found in IgG-multiple myeloma. Amyloid deposits and changes of the kidneys characteristic for the multiple myeloma appeared nearly in the same frequency in both types of multiple myeloma.

Adult↗
PubMed2025

Genomic characteristics and prognostic correlations in Chinese multiple myeloma patients.

BACKGROUND: Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of abnormal clonal plasma cells in the bone marrow. The heterogeneity in Chinese MM populations remains underexplored. METHODS: We conducted whole-exome sequencing (WES) on 241 tumor samples, complemented by RNA sequencing (RNA-seq) on 131 samples from 212 Chinese MM patients. RESULTS: We identified a novel mutational signature and analyzed molecular differences between newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) patients. NFKBIA mutations were notably more frequent in NDMM patients compared to the MMRF-COMMPASS cohort (4/50 vs 22/937, p = 0.048), with additional recurrent mutations in several genes like TTN, IGLL5 and SYNE1. In RRMM patients, UBR5 mutations were more prevalent (4/24 vs 0/50, p = 0.01), alongside frequent mutations in OBSCN, CACNA1H, and HSPG2. Clonal evolution was assessed through multiple time points and locations, identifying genes potentially linked to circulating plasma cell formation. Cox regression analysis revealed that age and mutations in OBSCN and RB1 were significant predictors of progression-free survival (PFS) in NDMM patients. Additionally, albumin, β2-microglobulin, and RB1 mutations were correlated with overall survival (OS). CONCLUSIONS: In summary, we characterized the genomic landscape of MM in diverse Chinese populations, confirmed clonal evolution, and identified prognostic genes.

Adult↗
PubMed1978

Multiple myeloma: an immunologic profile. II. Bone marrow studies.

Bone marrow mononuclear cell populations were studied in 35 patients without myeloma, 39 patients with multiple myeloma, and 15 patients with benign monoclonal gammopathy. Bone marrow mononuclear cell receptors, responses to mitogens or allogeneic stimuli, and suppressive effects on in vitro peripheral blood lymphocyte (PBL) function were studied. In bone marrow cell populations from patients with untreated multiple myeloma, the percent of complement receptor-bearing cells and the pokeweed mitogen- and concanavalin A-stimulated responses were significantly greater than were those in bone marrow cell populations from patients without myeloma. Sheep red blood cell receptor-bearing cells were significantly greater in marrow populations from treated multiple myeloma patients compared to those from untreated multiple myeloma patients. Sheep red blood cell receptor-bearing cells from the bone marrow of multiple myeloma patients suppressed responses of the multiple myeloma patients' PBL's to autologous mitomycin C-treated bone marrow plasma cells and to allogeneic stimuli in one-way mixed leukocyte culture. Complement receptor-bearing cells suppressed the response to pokeweed mitogen. The presence of lymphocytes in the marrow compartment that are capable of suppressing the response of myeloma patients' PBL's to plasma cell antigens may be significant in the pathogenesis of multiple myeloma.

Bone Marrow↗
PubMed1977

Fatal hepatic coma complicating oxymetholone therapy in multiple myeloma.

Two patients with multiple myeloma died in acute liver failure. Both had been treated with the anabolic steroid oxymetholone and both subsequently developed severe cholestatic hepatitis. In one the histological lesion progressed despite cessation of oxymetholone therapy. Myeloma infiltration of the liver and peliosis hepatis were not seen. As a fatal outcome from cholestatic hepatitis due to oxymetholone is rare it is possible that an unknown potentiating factor is present in multiple myeloma that can lead to a fatal outcome. If oxymetholone therapy is to be used in such patients then close clinical and laboratory assessment of liver function should be carried out in an attempt to prevent this unusual and fatal complication.

Cholestasis↗
PubMed1978

Pleural effusion--presenting sign in multiple myeloma.

A patient with multiple myeloma in whom recurrent right pleural effusion was the presenting sign of the disease is reported. An IgA (k) monoclonal component was found in both the pleural effusion and the serum. The bone marrow specimen was interpreted as typical for multiple myeloma and the pleural fluid contained numerous plasma cells. Treatment with cyclophosphamide was followed by clinical improvement and the disappearance of the pleural effusion.

Aged↗
PubMed1978

Pneumococcal bacteremia diagnosed by peripheral blood smear in multiple myeloma.

A patient with multiple myeloma and a normal spleen died with high-grade pneumococcal bacteremia diagnosed by routine examination of a Wright-stained peripheral blood smear. In earlier reports, this finding has been described only in patients with abnormal or absent spleens. We review the proposed mechanisms of high-grade pneumococcal bacteremia in these patients and the immunologic abnormalities in patients with multiple myeloma that may result in increased susceptibility to this infection.

Female↗
PubMed1978

Adriamycin, 1,3-bis (2-chloroethyl) 1 nitrosourea (BCNU, NSC No. 409962), cyclophosphamide plus prednisone (ABC-P) in melphalanresistant multiple myeloma.

Fourteen patients with multiple myeloma resistant to melphalan plus prednisone were treated with BCNU 50 mg/m2 plus cyclophosphamide 200 mg/m2 on day 1, adriamycin 20 mg/m2 on day 2 and prednisone 60 mg orally, daily for days 1 through 5. Therapy was repeated every four weeks. Depending upon criteria used, objective antitumor responses were achieved in five to nine of the 14 patients. Mean survival was 9.5 months and actuarial median survival was 7.0 months. Six patients are alive, four to 35 months after initiation of therapy. This preliminary report indicates that this combination may be a useful treatment program in the management of patients with advanced multiple myeloma. A review of studies employing adriamycin plus BCNU suggests that these regimens currently offer the most effective treatment of melphalan-resistant patients.

Aged↗