Kaaron Benson

Proteomic Contributions to Personalized Cancer Care

Cancer impacts each patient and family differently. Our current understanding of the disease is primarily limited to clinical hallmarks of cancer, but many specific molecular mechanisms remain elusive. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies that improve patient prognosis are not widely available for most cancers. Individualized care plans, also described as personalized medicine, still must be developed by understanding and implementing basic science research into clinical treatment. Proteomics holds great promise in contributing to the prevention and cure of cancer because it provides unique tools for discovery of biomarkers and therapeutic targets. As such, proteomics can help translate basic science discoveries into the clinical practice of personalized medicine. Here we describe how biological mass spectrometry and proteome analysis interact with other major patient care and research initiatives and present vignettes illustrating efforts in discovery of diagnostic biomarkers for ovarian cancer, development of treatment strategies in lung cancer, and monitoring prognosis and relapse in multiple myeloma patients.

Fatal group C streptococcal infection due to transfusion of a bacterially contaminated pooled platelet unit despite routine bacterial culture screening

BACKGROUND: An elderly man with chronic myelomonocytic leukemia developed respiratory distress and died less than 48 hours after transfusion of a pool of eight whole blood–derived platelets (PLTs). Blood cultures from the recipient and cultures of remnants from the pooled PLT bag grew group C streptococci (GCS). An investigation was conducted to identify both the infections source and the reasons for the false‐negative screening result.

Acute and delayed hemolytic transfusion reactions secondary to HLA alloimmunization

BACKGROUND: HLA antibodies may be directed against HLA antigens on RBCs, but these antibodies are generally not considered to be clinically significant in transfusion practice. A case of a multiparous woman who had hemolytic transfusion reactions due to HLA‐related Bg antibodies is reported.

Quantification of peptides from immunoglobulin constant and variable regions by LC‐MRM MS for assessment of multiple myeloma patients

Quantitative MS assays for Igs are compared with existing clinical methods in samples from patients with plasma cell dyscrasias, for example, multiple myeloma (MM).

Dispermic chimerism identified during HLA typing for stem cell transplantation.

BACKGROUND: Chimerism is defined as the presence of two genetically distinct cell populations in an organism. Few cases of phenotypically normal dispermic chimeras have been reported and most showed abnormalities on blood typing.

Anemia and Cancer

This chapter explores the management of anemia in older cancer patients. Cancer is a disease of aging: more than 50% of all malignancies currently occur in the 12% of the population aged 65 and over; by the year 2030 older individuals are expected to account for 20% of the population and 70% of all cancer cases (1). Though not unique of older individuals, anemia is a common manifestation of cancer, especially of advanced cancer (2). The elderly are expected to suffer disproportionately of cancer-related anemia, because cancer becomes more common with age and because age itself is a risk factor for anemia (1–3). Anemia is detrimental to cancer patients, because it compromises patient well-being, and it may increase the complications and reduce the benefits of antineoplastic treatment (2). Anemia of chronic inflammation (ACI) and of chemotherapy are the most common forms of anemia in cancer patients and both respond to pharmacological doses of erythropoietin (2, 4). The availability of a number of synthetic erythropoiesis-stimulating factors (ESF) that mimic the action of erythropoietin has allowed the correction of anemia in the majority of cancer patients. After reviewing the pathogenesis of anemia we will examine the consequences of anemia for the older cancer patients and the benefits and potential risks of treatment with ESF.

Leptomeningeal Myeloma As the Sole Manifestation of Relapse: An Unusual Presentation

We report a case of a 57-year-old African American male patient with standard risk (IIIA) IgA kappa multiple myeloma. This patient presented with neurologic complaints (manifesting as generalized muscle weakness and swallowing dysfunction associated with a poor cough reflex) 10 months after achieving a very good partial remission and without evidence of systemic progression. Examination of the cerebrospinal fluid revealed leptomeningeal involvement. Very little is known about the mechanisms of myelomatous spread to the leptomeninges, a very rare event, and the presentation of this case could raise awareness of this rare complication in those involved in caring for patients with multiple myeloma.

A novel approach to improving efficiency and cost saving in preoperative blood preparation

Preoperative ordering of blood products has been an area of optimization due to considerable variability among physicians; overpreparation can lead to extra costs and underpreparation of blood can potentially compromise patient safety.

Abstract 5557: Quantitative mass spectrometry assays for antibodies to measure multiple myeloma tumor burden and detect relapse

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC a) The goal of this study is to develop and characterize mass spectrometry assays for antibody quantification to assess multiple myeloma patients; the results generated from these peptide-based techniques will be compared data generated with gel-based and capillary serum protein electrophoresis (SPEP), which represents the current standard of care. b) Monoclonal antibody concentrations are currently determined using protein electrophoresis with either serum aliquots (SPEP) or Urine samples (UPEP), the specific class of myeloma is then determined using immunofixation. Liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM) assays have been developed to quantify all antibodies (Ig G, A, M, D, E, kappa, and lambda) and their isoforms in serum samples by measuring against known concentrations of stable isotope labeled internal standards using a triple quadrupole mass spectrometer. For assay development, at least two peptides representing each antibody isoform were derived from either LC-MS/MS runs based on excised gamma bands from stored SPEP gels of previous myeloma patients; these experimental results could also be supplemented by in silico workup of the protein sequence (i.e. theoretical peptide predictions). For each peptide target, several transitions (pairs of intact peptide masses and fragment ion masses) are programmed into the triple quadrupole for targeted detection using LC-MRM. Samples are analyzed in triplicate and compared with SPEP results. c) LC-MRM analysis has been performed on more than 40 serum samples collected from multiple myeloma patients. Using the selected peptides, protein amounts were calculated and compared with previous clinical SPEP results. The panel of antibodies presents unique opportunities and challenges for examining the utility of LC-MRM monitoring; for example, IgD and IgE increases can be detected with LC-MRM well below the 1 mg/ml limit of SPEP (at approximately 20 micrograms/ml). On the other hand, quantification of IgG1 with LC-MRM must be extremely accurate (< 10% CV) to detect the monoclonal protein against the background of that protein normally found in serum. To date, LC-MRM can detect all SPEP positive patients, and this method shows promise in detecting increases in antibody concentrations before they can be detected with SPEP. d) Quantitative mass spectrometry measurements for the antibodies combine the value of current SPEP and immunofixation experiments. Our results show that peptide-based monitoring can be as effective as protein-based monitoring. In addition, LC-MRM can detect light chain only disease, IgA myeloma that do not present a clear band in the gamma region of SPEP, and oligoclonal or polyclonal disease. These data enable broader commentary on the utility of LC-MRM in clinical protein measurements. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5557.