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Blood Jun 2024
Azab AK, Runnels JM, Pitsillides C, et al. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood. 2009;113(18):4341-4351.
Topics: Cyclams; Humans; Multiple Myeloma; Receptors, CXCR4; Benzylamines; Heterocyclic Compounds; Bone Marrow; Tumor Microenvironment
PubMed: 38900482
DOI: 10.1182/blood.2024025275 -
Blood Jun 2024
Azab AK, Azab F, Blotta S, et al. RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma. Blood. 2009;114(3):619-629.
Topics: Humans; rhoA GTP-Binding Protein; Multiple Myeloma; rac1 GTP-Binding Protein; Chemokine CXCL12; Cell Adhesion; Chemotaxis
PubMed: 38900475
DOI: 10.1182/blood.2024025276 -
Blood Jun 2024
Topics: Multiple Myeloma; Humans; Immunotherapy
PubMed: 38900472
DOI: 10.1182/blood.2024024709 -
Blood Jun 2024
Azab AK, Quang P, Azab F, et al. P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood. 2012;119(6):1468-1478.
Topics: Multiple Myeloma; Humans; Bone Marrow; Tumor Microenvironment; Membrane Glycoproteins; P-Selectin
PubMed: 38900471
DOI: 10.1182/blood.2024024988 -
Blood Jun 2024
Houde CA, Khan A, Jacobus SJ, et al. Treatment outcomes and prognostic factors with lenalidomide, bortezomib, and dexamethasone (RVd) alone versus Rvd plus autologous stem cell transplantation (ASCT) in African American (AA) patients (Pts) with newly diagnosed multiple myeloma (NDMM) in the...
Topics: Humans; Multiple Myeloma; Dexamethasone; Lenalidomide; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Transplantation, Autologous; Black or African American; Prognosis; Hematopoietic Stem Cell Transplantation; Treatment Outcome; Male; Female; Middle Aged
PubMed: 38900470
DOI: 10.1182/blood.2024025081 -
Oncology (Williston Park, N.Y.) Jun 2024The June Hot Topics focuses on the challenges venetoclax regimens have faced in multiple myeloma trials.
The June Hot Topics focuses on the challenges venetoclax regimens have faced in multiple myeloma trials.
Topics: Multiple Myeloma; Humans; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Chromosomes, Human, Pair 14; Antineoplastic Agents; Translocation, Genetic; Chromosomes, Human, Pair 11; Clinical Trials as Topic; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38899981
DOI: 10.46883/2024.25921023 -
BMC Medical Genomics Jun 2024Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis...
BACKGROUND
Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM.
METHODS AND RESULTS
The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constructed through single-factor and multiple-factor analysis. The ROC curve was plotted to compare the survival difference between high- and low-risk groups. The nomogram was used to validate the predictive capability of the risk model. A total of 87 ubiquitination-related genes were obtained, with 47 genes showing high expression in the MM group. According to the consistent cluster analysis, 4 clusters were determined. The immune infiltration, survival, and prognosis differed significantly among the 4 clusters. The tumor purity was higher in clusters 1 and 3 than in clusters 2 and 4, while the immune score and stromal score were lower in clusters 1 and 3. The proportion of B cells memory, plasma cells, and T cells CD4 naïve was the lowest in cluster 4. The model genes KLHL24, HERC6, USP3, TNIP1, and CISH were highly expressed in the high-risk group. AICAr and BMS.754,807 exhibited higher drug sensitivity in the low-risk group, whereas Bleomycin showed higher drug sensitivity in the high-risk group. The nomogram of the risk model demonstrated good efficacy in predicting the survival of MM patients using TCGA and GEO datasets.
CONCLUSIONS
The risk model constructed by ubiquitination-related genes can be effectively used to predict the prognosis of MM patients. KLHL24, HERC6, USP3, TNIP1, and CISH genes in MM warrant further investigation as therapeutic targets and to combat drug resistance.
Topics: Humans; Multiple Myeloma; Computational Biology; Prognosis; Ubiquitination; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Nomograms; Cluster Analysis
PubMed: 38898455
DOI: 10.1186/s12920-024-01937-0 -
BMC Ophthalmology Jun 2024Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with...
BACKGROUND
Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy.
CASE PRESENTATION
a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity.
CONCLUSIONS
Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease.
Topics: Humans; Aged; Female; Diagnosis, Differential; Corneal Diseases; Paraproteinemias; Tomography, Optical Coherence
PubMed: 38898421
DOI: 10.1186/s12886-024-03487-6 -
Nature Communications Jun 2024GPRC5D is an atypical Class C orphan G protein-coupled receptor. Its high expression on the surface of multiple myeloma cells has rendered it an attractive target for...
GPRC5D is an atypical Class C orphan G protein-coupled receptor. Its high expression on the surface of multiple myeloma cells has rendered it an attractive target for therapeutic interventions, including monoclonal antibodies, CAR-T cells, and T-cell engagers. Despite its therapeutic potential, the insufficient understanding regarding of the receptor's structure and antibody recognition mechanism has impeded the progress of effective therapeutic development. Here, we present the structure of GPRC5D in complex with a preclinical-stage single-chain antibody (scFv). Our structural analysis reveals that the GPRC5D presents a close resemblance to the typical Class C GPCRs in the transmembrane region. We identify a distinct head-to-head homodimer arrangement and interface mainly involving TM4, setting it apart from other Class C homo- or hetero-dimers. Furthermore, we elucidate the binding site engaging a sizable extracellular domain on GPRC5D for scFv recognition. These insights not only unveil the distinctive dimer organization of this unconventional Class C GPCR but also hold the potential to advance drug development targeting GPRC5D for the treatment of multiple myeloma.
Topics: Humans; Multiple Myeloma; Receptors, G-Protein-Coupled; Single-Chain Antibodies; Protein Multimerization; Protein Binding; Binding Sites; Antibodies, Monoclonal
PubMed: 38898050
DOI: 10.1038/s41467-024-49625-y -
EJHaem Jun 2024Multiple myeloma (MM) is a disease, that at times poses diagnostic and monitoring challenges. Over the last decades laboratory methods have been expanded with serum free...
Multiple myeloma (MM) is a disease, that at times poses diagnostic and monitoring challenges. Over the last decades laboratory methods have been expanded with serum free light chain (FLC) analysis. Alerted by two index cases with clinical impact due to failure of the FLC analysis to indicate a disease progression, we aimed to identify any clinical consequences due to known differences between FLC analysis methods. We applied two FLC analysis methods (Freelite Binding Site [FBS] and N-Latex Siemens [NLS]) on all patients with MM and monoclonal gammopathy of uncertain significance diagnosed/followed up at Södra Älvsborg Hematology Unit, from April to December 2022. From a total of 123 patients with malignant plasma cell disorder, we identified five cases (4.1%) where solely the FBS method, as opposed to NLS, urine and serum electrophoresis, could support diagnosis or detect progression. The consequences of this discrepancy included not only change of diagnosis or delayed therapy but also change of treatment. Our findings indicate that a stronger awareness of the potential weaknesses of different FLC methods is needed, which calls for a closer collaboration between clinical chemists and hematologists.
PubMed: 38895087
DOI: 10.1002/jha2.886