Research in Dr. Fonseca's Multiple Myeloma Laboratory focuses mainly on the progression of multiple myeloma, from its origins in the precancerous condition monoclonal gammopathy of undetermined significance (MGUS), and on related chromosomal abnormalities and their significance in patient outcomes.
Dr. Fonseca is also involved in clinical trials for multiple myeloma, and our lab has expertise in the collection and processing of bone marrow and peripheral blood samples that can be used for cell culture, drug testing and genetic ascertainment in support of correlative science and tissue banking.
Our research projects include:
- Origin of the MGUS clone and genomic instability
- Progression from MGUS to myeloma
- Clinical significance of chromosomal abnormalities in myeloma
- Molecular studies of genetic abnormalities in clonal cells of light chain amyloidosis
- Molecular studies of genetic abnormalities in clonal cells of Waldenstrom macroglobulinemia
Origin of the MGUS clone and genomic instability
We launched a systematic evaluation of MGUS plasma cells by molecular and cytogenetic methods. Our goal is to understand the nature of the clone, the clinical and biological significance of the abnormalities, and the order of acquisition of abnormalities. We're also investigating factors permissive for the significant genomic instability observed in the plasma cell neoplasms, such as centrosome amplification.
Progression from MGUS to myeloma
We want to better understand why some patients with monoclonal gammopathy of undetermined significance develop multiple myeloma and why some never do, and which abnormalities are acquired and important for disease progression. We've done a genetic characterization of the risk of progression in MGUS according to cytogenetic status. We also have described the presence of IgH translocations in MGUS cells, even those associated with aggressive clinical behavior in myeloma. We have shown the presence of hyperdiploid and nonhyperdiploid dichotomy in MGUS.
Clinical significance of chromosomal abnormalities in myeloma
Our research team investigates the clinical, biological and prognostic implications of specific chromosomal and genetic abnormalities in patients with myeloma. We believe that gaining a better understanding about the abnormalities underlying myeloma will allow for better disease management and treatment, ultimately improving patient outcomes. We have described the negative impact on prognosis of some genetic aberrations and better outcomes with others. We also have shown different pathology and clinical features of myeloma based on this genetic characterization. We performed a series of studies to comprehensively characterize hyperdiploid myeloma, the most common genetic subtype of myeloma, and have identified new prognostically important subtypes.
Molecular studies of genetic abnormalities in clonal cells of light chain amyloidosis
We're investigating the nature of the clone and its relation to the protein abnormality. We're also exploring the features of the light chains that make them amyloidogenic.
Molecular studies of genetic abnormalities in clonal cells of Waldenstrom macroglobulinemia
Our studies have focused on the genetic abnormalities of clonal cells of patients with macroglobulinemia and their relation to other B-cell malignancies. Our lab described the presence of losses in chromosome 6 in nearly half the patients with Waldenstrom macroglobulinemia and showed that these cells lack heavy chain translocations, including the t(9;14), resulting in PAX5 upregulation.