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American Journal of Hematology Jun 2024Multiple myeloma accounts for approximately 10% of hematologic malignancies.
DISEASE OVERVIEW
Multiple myeloma accounts for approximately 10% of hematologic malignancies.
DIAGNOSIS
The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L and urine monoclonal protein is ≥200 mg/24 h), or >1 focal lesion on magnetic resonance imaging.
RISK STRATIFICATION
The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, or p53 mutation is considered high-risk multiple myeloma. Presence of any two high risk factors is considered double-hit myeloma; three or more high risk factors is triple-hit myeloma.
RISK-ADAPTED INITIAL THERAPY
In patients who are candidates for autologous stem cell transplantation, induction therapy consists of anti-CD38 monoclonal antibody plus bortezomib, lenalidomide, dexamethasone (VRd) followed by autologous stem cell transplantation (ASCT). Selected standard risk patients can delay transplant until first relapse. Frail patients who not candidates for transplant are treated with VRd for approximately 8-12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression.
MAINTENANCE THERAPY
Standard risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high-risk myeloma.
MANAGEMENT OF RELAPSED DISEASE
A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse. Chimeric antigen receptor T (CAR-T) cell therapy and bispecific antibodies are additional options.
PubMed: 38943315
DOI: 10.1002/ajh.27422 -
Frontiers in Bioscience (Landmark... May 2024Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant...
BACKGROUND
Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis.
METHODS
The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB).
RESULTS
PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated.
CONCLUSION
PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.
Topics: Humans; Osteosarcoma; RNA, Long Noncoding; Ferroptosis; STAT3 Transcription Factor; Cell Line, Tumor; Bone Neoplasms; Phospholipid Hydroperoxide Glutathione Peroxidase; Cell Proliferation; Reactive Oxygen Species; Signal Transduction; Cell Movement; Disease Progression; Apoptosis; Gene Expression Regulation, Neoplastic
PubMed: 38940027
DOI: 10.31083/j.fbl2906207 -
Frontiers in Oncology 2024Extramedullary plasmacytoma (EMP) is an uncommon solitary tumor originating from neoplastic plasma cells located outside the bone marrow. Despite its rarity, the...
INTRODUCTION
Extramedullary plasmacytoma (EMP) is an uncommon solitary tumor originating from neoplastic plasma cells located outside the bone marrow. Despite its rarity, the occurrence of EMP without a concurrent diagnosis of multiple myeloma (MM) is considered extremely rare. Approximately 80-90% of EMP cases are found in the head and neck region, with a higher incidence in men aged between 50 and 60 years. The current treatment modalities include radiotherapy (RT) as a first-line approach, with surgery or chemotherapy regarded as other therapeutic options. While RT proves effective in the majority of EMP cases, there are instances where the tumor remains refractory to radiation. In this case report, we present an unusual scenario of EMP resistant to RT without concurrent signs of multiple myeloma which was successfully treated with surgery followed by systemic therapy.
CASE REPORT
A 72-year-old male was admitted to the Head and Neck Cancer Clinic with a 6-month history of swallowing difficulties. He denied experiencing weight loss or pain on swallowing. Basic laboratory tests yielded results within normal limits, except for beta-2 microglobulin. Physical examination revealed an enlarged submandibular lymph node on the right side. Fiberoptic examination identified a soft tissue polypoid mass within the right piriform fossa, slightly protruding into the vocal slit. A CT scan displayed a well-circumscribed 2 cm polypoid, homogeneously enhancing soft tissue mass adjacent to the posterior surface of the epiglottis and the right side of the tongue base. Bone marrow biopsy revealed no abnormalities, and there were no clinical or laboratory signs of multiple myeloma. Based on the tumor biopsy results and imaging studies, a diagnosis of EMP was made. Due to the lack of response to RT, surgical removal of the tumor was pursued, followed by systemic therapy. Ultimately, the patient achieved full recovery with effective disease control.
CONCLUSION
In conclusion, EMP without concurrent multiple myeloma is an exceedingly rare condition that demands a multidisciplinary approach for both diagnosis and treatment. Moreover, although RT continues to be the primary standard treatment for EMP, in some cases other therapeutic regimens prove to be successful.
PubMed: 38912063
DOI: 10.3389/fonc.2024.1353943 -
Journal of Radiology Case Reports 2024Multiple myeloma is a plasma cell neoplasm, which may present as a solitary plasmacytoma and, uncommonly, as an extramedullary plasmacytoma. Intracranial plasmacytomas...
Multiple myeloma is a plasma cell neoplasm, which may present as a solitary plasmacytoma and, uncommonly, as an extramedullary plasmacytoma. Intracranial plasmacytomas may manifest in central nervous system involvement as cranial nerve palsies. Cranial nerve six palsy is the most common in cases of malignancy. However, isolated abducens palsy presenting as multiple myeloma recurrence is very uncommon. Here, we detail two cases in which intracranial plasmacytoma lesions were present within the region of the Dorello canal, resulting in acute isolated unilateral diplopia from disease recurrence in the absence of systemic marrow involvement.
Topics: Humans; Abducens Nerve Diseases; Multiple Myeloma; Neoplasm Recurrence, Local; Male; Magnetic Resonance Imaging; Middle Aged; Aged; Diagnosis, Differential; Plasmacytoma; Female; Diplopia; Brain Neoplasms
PubMed: 38910589
DOI: 10.3941/jrcr.v18i1.5240 -
Cureus Jun 2024Plasmacytomas rarely affect the skull base and may be found as an isolated lesion or as a part of multiple myeloma. The typical feature of plasmacytomas is aggressive...
Plasmacytomas rarely affect the skull base and may be found as an isolated lesion or as a part of multiple myeloma. The typical feature of plasmacytomas is aggressive bone destruction in the skull. It is often confused with the chordoma of the clivus. The most common location for skull-base plasmacytomas is the nasopharynx. The most commonly affected cranial nerve in clivus tumors is the abducens nerve. In our 64-year-old male case, a plasmacytoma was detected in the clivus. There was ptosis and decreased vision due to optic nerve and oculomotor nerve involvement due to the plasmacytoma. Radiotherapy was applied for the treatment.
PubMed: 38882228
DOI: 10.7759/cureus.62447 -
OTO Open 2024
PubMed: 38863484
DOI: 10.1002/oto2.144 -
BMJ Case Reports Jun 2024Multiple myeloma associated with extramedullary plasmacytoma at initial presentation is rare. We describe a case of a man in his 30s who initially presented with...
Multiple myeloma associated with extramedullary plasmacytoma at initial presentation is rare. We describe a case of a man in his 30s who initially presented with symptoms of spinal cord compression. Further imaging revealed a mediastinal tumour, with a biopsy confirming plasmacytoma. Immunofixation revealed IgA lambda paraprotein. Bone marrow biopsy demonstrated atypical T-cell cytotoxic proliferation and trilineage hypoplasia. The patient was diagnosed with extramedullary plasmacytoma with active IgA multiple myeloma. The patient received mediastinal radiation to the tumour, followed by anti-myeloma therapy. This diagnosis is critical as managing a solitary plasmacytoma drastically differs from an extramedullary plasmacytoma with active multiple myeloma.
Topics: Humans; Male; Multiple Myeloma; Spinal Cord Compression; Plasmacytoma; Mediastinal Neoplasms; Immunoglobulin A; Adult; Magnetic Resonance Imaging; Diagnosis, Differential
PubMed: 38844357
DOI: 10.1136/bcr-2023-257026 -
Journal of Veterinary Diagnostic... Jul 2024Cytologic evaluation of aspirate slides from a small, <1-cm, interdigital mass on a 9-y-old, spayed female Yorkshire Terrier revealed a proliferation of discrete, round...
Cytologic evaluation of aspirate slides from a small, <1-cm, interdigital mass on a 9-y-old, spayed female Yorkshire Terrier revealed a proliferation of discrete, round cells containing few-to-many, variably sized, round, eosinophilic, cytoplasmic inclusions. The top differentials based on the cytologic findings were either a plasma cell tumor or a B-cell lymphoma with Mott cell differentiation. The unencapsulated, well-demarcated, multilobulated round-cell neoplasm was completely excised. Immunohistochemical stains were performed to further characterize the neoplasm, which had immunolabeling for multiple myeloma oncogene 1 and vimentin, but did not react with CD3, CD20, melan A, or ionized calcium-binding adapter molecule 1, nor with a Giemsa special stain. Ultrastructurally, the cytoplasmic granules had Russell body-like morphology. A solitary, cutaneous plasmacytoma with Mott cell differentiation has not been described previously in veterinary medicine, to our knowledge.
Topics: Animals; Dogs; Dog Diseases; Plasmacytoma; Female; Skin Neoplasms; Cell Differentiation; Diagnosis, Differential
PubMed: 38842410
DOI: 10.1177/10406387241251840 -
Scientific Reports Jun 2024Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis...
Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and metastasis. However, whether cuproptosis-related lncRNAs are involved in the pathogenesis of diffuse large B cell lymphoma (DLBCL) remains unclear. This study aimed to identify the prognostic signatures of cuproptosis-related lncRNAs in DLBCL and investigate their potential molecular functions. RNA-Seq data and clinical information for DLBCL were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Cuproptosis-related lncRNAs were screened out through Pearson correlation analysis. Utilizing univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis, we identified seven cuproptosis-related lncRNAs and developed a risk prediction model to evaluate its prognostic value across multiple groups. GO and KEGG functional analyses, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. Additionally, drug sensitivity analysis identified drugs with potential efficacy in DLBCL. Finally, the protein-protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). We identified a set of seven cuproptosis-related lncRNAs including LINC00294, RNF139-AS1, LINC00654, WWC2-AS2, LINC00661, LINC01165 and LINC01398, based on which we constructed a risk model for DLBCL. The high-risk group was associated with shorter survival time than the low-risk group, and the signature-based risk score demonstrated superior prognostic ability for DLBCL patients compared to traditional clinical features. By analyzing the immune landscapes between two groups, we found that immunosuppressive cell types were significantly increased in high-risk DLBCL group. Moreover, functional enrichment analysis highlighted the association of differentially expressed genes with metabolic, inflammatory and immune-related pathways in DLBCL patients. We also found that the high-risk group showed more sensitivity to vinorelbine and pyrimethamine. A cuproptosis-related lncRNA signature was established to predict the prognosis and provide insights into potential therapeutic strategies for DLBCL patients.
Topics: Lymphoma, Large B-Cell, Diffuse; Humans; RNA, Long Noncoding; Prognosis; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Protein Interaction Maps; Male; Female; Gene Expression Profiling; Gene Regulatory Networks; Middle Aged
PubMed: 38839842
DOI: 10.1038/s41598-024-63433-w -
Cancer Reports (Hoboken, N.J.) Jun 2024Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study...
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study aimed to clarify the role of the lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC growth and metastasis.
METHODS
Differentially expressed lncRNAs in CRC were analyzed using the Cancer Genome Atlas. Gene expression profiling interactive analysis and a comprehensive resource for lncRNAs from cancer arrays databases were used to analyze lncRNA PVT1 expression and CRC prognosis, respectively. Cell counting kit-8, wound healing, colony formation, Transwell, and immunofluorescence assays were used to evaluate CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), respectively. Tumor growth and metastasis models were used to explore the PVT1 effect on the growth and metastasis of CRC in vivo.
RESULTS
PVT1 was highly expressed in CRC, associated with a poor prognosis of CRC, and showed good diagnostic value. Transfection of sh-PVT1 or pcDNA3.1-PVT1 reduced or increased the proliferation, wound healing rate, colony formation, invasion, and EMT of CRC cells. PVT1 and miR-3619-5p were co-expressed in CRC cytoplasm, and PVT1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-3619-5p to up-regulate tripartite motif containing 29 (TRIM29) expression. MiR-3619-5p overexpression and TRIM29 knockdown reduced proliferation, wound healing rate, invasion, and EMT of CRC cells. However, simultaneous PVT1 and miR-3619-5p overexpression or knockdown of miR-3619-5p and TRIM29 knockdown rescued the malignant phenotype of CRC cells.
CONCLUSIONS
We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.
Topics: Humans; Colorectal Neoplasms; RNA, Long Noncoding; MicroRNAs; Cell Proliferation; Gene Expression Regulation, Neoplastic; Mice; Animals; Cell Movement; Prognosis; Epithelial-Mesenchymal Transition; Transcription Factors; Male; DNA-Binding Proteins; Mice, Nude; Female; Cell Line, Tumor; Neoplasm Metastasis; Mice, Inbred BALB C; Xenograft Model Antitumor Assays
PubMed: 38837682
DOI: 10.1002/cnr2.2085