Publications by authors named "Raphael Szalat"
Article Synopsis
- Kidney light chain (AL) amyloidosis can lead to serious health issues including the need for kidney replacement therapy and increased mortality risk, with better outcomes linked to significant reductions in proteinuria after treatment.
- This study aimed to confirm how different levels of kidney response to treatment relate to patient survival, using data from 732 patients over several years.
- Results showed that deeper kidney responses within 6 months of treatment initiation were associated with significantly lower chances of needing kidney replacement therapy after 5 years.
The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow stromal cells provide growth and survival signals, thereby promoting the development of drug resistance. Here, we show that the interaction between bone marrow stromal cells and myeloma cells (using human cell lines) induces chromatin remodeling of cis-regulatory elements and is associated with changes in the expression of genes involved in the cell migration and cytokine signaling.
View Article and Find Full Text PDFMultiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells. MM is a heterogeneous disease, featured by various molecular subtypes with different outcomes. With the advent of very efficient therapies including monoclonal antibodies, bispecific T-cell engagers and chimeric antigen receptor T cells (CAR T cells), most MM patients now have a prolonged survival.
View Article and Find Full Text PDFBackground: Obesity is an established risk factor for multiple myeloma (MM). Relatively few prior studies, however, have evaluated associations in Black populations.
Methods: Among 55,276 participants in the Black Women's Health Study, a prospective U.
In a short time, single-cell platforms have become the norm in many fields of research, including multiple myeloma (MM). In fact, the large amount of cellular heterogeneity in MM makes single-cell platforms particularly attractive because bulk assessments can miss valuable information about cellular subpopulations and cell-to-cell interactions. The decreasing cost and increasing accessibility of single-cell platform, combined with breakthroughs in obtaining multiomics data for the same cell and innovative computational programs for analyzing data, have allowed single-cell studies to make important insights into MM pathogenesis; yet, there is still much to be done.
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- High-dose melphalan (HDM) leads to improved progression-free survival in multiple myeloma, but it also significantly increases mutations in myeloma cells at relapse compared to those treated without HDM.
- In a study of 68 patients, those receiving HDM showed a notable rise in mutations from diagnosis to relapse, indicating potential DNA damage effects, while mutation rates at diagnosis were similar across treatment groups.
- A machine learning model distinguished patients receiving HDM based on mutation patterns, revealing that while HDM treatment led to clonal selection and more subclonal mutations, patients achieving complete remission still had comparable survival rates to those treated with RVD, possibly due to a greater number of neoantigens in the HDM
Purpose: Binary cardiac response assessment using cardiac biomarkers is prognostic in light chain amyloidosis. Previous studies suggested four-level cardiac responses using N-terminal prohormone of brain natiuretic peptide improves prognostic prediction. This study was designed to validate graded cardiac response criteria using N-terminal prohormone of brain natiuretic peptide/brain natiuretic peptide.
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- High-dose melphalan and stem cell transplantation (HDM/SCT) shows long-term effectiveness in treating AL amyloidosis, with 39% of patients achieving complete hematologic response (CR).
- The median CR duration is 12.3 years, while overall survival (OS) for patients with CR is impressive, reaching up to 15 years for some.
- Factors such as elevated dFLC levels and plasma cell percentages are linked to shorter event-free survival (EFS), allowing the development of a risk score to better predict outcomes.
Article Synopsis
- Immunoglobulin M (IgM) multiple myeloma (MM) is a rare condition that needs to be differentiated from other similar diseases, such as Waldenström macroglobulinemia, for effective treatment.
- The study involved analyzing genomic and transcriptomic data of IgM-MM samples through whole-genome and transcriptome sequencing, revealing shared characteristics with MM, but unique features like specific chromosomal translocations and deletions.
- Findings indicated that IgM-MM likely originates before the germinal center stage, highlighted by unique molecular signatures and elevated expression of potential therapeutic targets, such as CD20 and Bruton tyrosine kinase.
Article Synopsis
- Daratumumab, either alone (sDARA) or in combination with chemotherapy (cDARA), shows strong effectiveness in treating AL amyloidosis, with high rates of hematologic response.
- In a study of 107 patients, the median major organ deterioration progression-free survival (MOD-PFS) was significantly better for the cDARA group, while patients receiving more than 12 cycles of treatment had longer MOD-PFS and overall survival (OS).
- Key predictive factors for worse outcomes included high NTproBNP levels, specific genetic markers, and a shorter duration of treatment, emphasizing the need for careful patient monitoring.
Article Synopsis
- Multiple myeloma (MM) is more common in African Americans (AAs), and younger AA patients (<65 years) show better overall survival than younger White patients despite equal healthcare access.
- In a study of 2243 VA patients, the deletion of chromosome 17p (del17p), which is linked to worse prognosis, was found less frequently in AAs (5.56%) compared to Whites (10.52%).
- There was no significant difference in survival for both races among patients with del17p, but younger AAs without del17p still had a notable survival advantage over their White counterparts, implying other factors contribute to their better outcomes.
Article Synopsis
- Many studies have explored how changes in mitochondrial DNA (mtDNA) are linked to cancer development, but the specifics in multiple myeloma (MM) are still not well understood.
- In this study, researchers found that mtDNA copy number (mtDNACN) significantly increased in MM cells compared to healthy cells, and higher mtDNACN correlated with worse progression-free survival outcomes in newly diagnosed MM patients.
- The findings suggest that the activation of mitochondrial biogenesis plays a role in myeloma cell transformation, indicating potential treatment targets and the importance of monitoring mtDNACN for better clinical management of high-risk conditions like smoldering multiple myeloma (SMM).
Article Synopsis
- - Multiple myeloma (MM) is a complex cancer marked by the growth of abnormal plasma cells and instability in its genetic makeup.
- - Advances in next-generation sequencing have revealed various genetic changes in MM, such as gene translocations and mutations, which can categorize patients into different molecular groups with varying prognoses.
- - Identifying these recurring genomic abnormalities can help develop better prediction models for patient outcomes and guide treatment decisions throughout the disease progression.
Article Synopsis
- Emerging data indicate that cancer patients show variability in susceptibility and outcomes to COVID-19, necessitating the identification of associated risk factors for better healthcare recommendations.
- An analysis of electronic health records revealed that among 22,914 cancer patients tested for COVID-19, 7.8% tested positive, with higher rates in African Americans and those with hematologic malignancies.
- The study found that older age and comorbidities significantly impacted COVID-19 mortality in cancer patients, but race and recent treatment did not influence overall outcomes.
Purpose: Multiple myeloma (MM) is accompanied by heterogeneous somatic alterations. The overall goal of this study was to describe the genomic landscape of myeloma using deep whole-genome sequencing (WGS) and develop a model that identifies patients with long survival.
Methods: We analyzed deep WGS data from 183 newly diagnosed patients with MM treated with lenalidomide, bortezomib, and dexamethasone (RVD) alone or RVD + autologous stem cell transplant (ASCT) in the IFM/DFCI 2009 study (ClinicalTrials.
Article Synopsis
- Genomic instability (GIN) is a key feature in cancer, with variations in its occurrence and causes across different types, including multiple myeloma (MM).
- MM progresses through stages of genomic changes, which are being mapped through next-generation sequencing (NGS) to understand how these alterations contribute to cancer development.
- Despite driving disease progression, GIN also exposes weaknesses in tumors that can be targeted for treatment, highlighting potential therapeutic strategies that focus on these vulnerabilities.
UBE2T is frequently amplified and/or overexpressed and is required for homologous recombination activity in multiple myeloma cells. UBE2T is a potential therapeutic target to increase chemosensitivity in multiple myeloma cells.
View Article and Find Full Text PDFHomologous recombination deficiency conferred by alterations in BRCA1 or BRCA2 are common in breast tumors and can drive sensitivity to platinum chemotherapy and PARP inhibitors. Alterations in nucleotide excision repair (NER) activity can also impact sensitivity to DNA damaging agents, but NER activity in breast cancer has been poorly characterized. Here, we apply a novel immunofluorescence-based cellular NER assay to screen a large panel of breast epithelial and cancer cell lines.
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