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  • American Society of Hematology  (7)
  • Nature Publishing Group  (1)
  • 2005-2009  (8)
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  • 1
    Electronic Resource
    Electronic Resource
    Ecology A niche for cyanobacteria containing chlorophyll d (2005)
    [s.l.] : Nature Publishing Group
    Nature 433 (2005), S. 820-820 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The cyanobacterium known as Acaryochloris marina is a unique phototroph that uses chlorophyll d as its principal light-harvesting pigment instead of chlorophyll a, the form commonly found in plants, algae and other cyanobacteria; this means that it depends on far-red light for ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/433820a
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  • 2
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    Possible roles for activating RAS mutations in the MGUS to MM transition and in the intramedullary to extramedullary transition in some plasma cell tumors (2005)
    American Society of Hematology
    Details
    Publication Date: 2005-01-01
    Description: To assess a possible role in tumor progression, the occurrence and type of K- and N-RAS mutations were determined in purified tumor cells, including samples from patients with premalignant monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and extramedullary plasma cell (PC) tumors (ExPCTs). Immunophenotypic aberrant PCs were flow sorted from 20 MGUS, 58 MM, and 13 ExPCT patients. One RAS mutation was identified in 20 MGUS tumors (5%), in contrast to a much higher prevalence of RAS mutations in all stages of MM (about 31%). Further, oncogene analyses showed that RAS mutations are not evenly distributed among different molecular subclasses of MM, with the prevalence being increased in MM-expressing cyclin D1 (P = .015) and decreased in MM with t(4;14) (P = .055). We conclude that RAS mutations often provide a genetic marker if not a causal event in the evolution of MGUS to MM. Surprisingly, RAS mutations were absent in bone marrow tumor cells from all patients with ExPCT, a result significantly different from intramedullary MM (P = .001). From 3 of 6 patients with paired intramedullary and extramedullary PCs and identical immunoglobulin heavy chain gene (IgH) sequences, RAS mutations were identified only in extramedullary PCs, suggesting a role for RAS mutations in the transition from intramedullary to extramedullary tumor. (Blood. 2005;105:317-323)
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    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
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    Patterns of Monoclonal Immunoglobulins and Serum Free Light Chains Are Significantly Different in African-American Compared to Caucasian MGUS Patients. (2009)
    American Society of Hematology
    Details
    Publication Date: 2009-11-20
    Description: Abstract 2838 Poster Board II-814 Background. Monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma (MM), is 2- to 3-fold more common in African-Americans (AA) than Caucasians (CA). Prior studies have reported clinical features of MGUS and MM to be different among AA compared to CA. Recent studies on CA MGUS cases have found serum free kappa and lambda light chain assays (sFLC) to be highly predictive of MM progression. We have conducted the first study designed to evaluate patterns of sFLC markers in AA. Methods. All AA MGUS patients seen at Walter Reed Army Medical Center (WR) and the Washington DC Veteran's Affairs Medical Center (VA) 2005-2009 were eligible. WR patients were enrolled through a retrospective chart review as sFLC has been performed routinely on MGUS patients. VA patients were enrolled in a prospective trial and sFLC was performed at WR. All patients were categorized for their risk of progression using the Mayo Clinic model (Rajkumar SV Blood 2005) and compared to the Caucasian Mayo Clinic population by the Fisher's exact test (2-tailed). Results. Eighty-six patients were enrolled, the median age was 73 yrs (42-92) and 74% were male. The MGUS isotype was 87% IgG, 10% IgA, 2% IgM and 1% biclonal. Kappa and lambda light chain disorders were present in 61% and 38%, respectively. The median monoclonal Ig concentration was 0.56 gm/dL (trace-2.33), 47% had a concentration '0.5 g/dL, 30% 0.51-1.0, 20% 1-2 g/dL, and 2% 2-3 g/dL. An abnormal sFLC ratio was present in 49% of patients. Based on the Mayo Clinic model, the risk of progression was: low 42% (95%CI 32-52), low-intermediate 49% (39-59), high-intermediate 8% (4-16) and high 1% (0-7). In comparing our data to the Mayo Clinic data, AA have significantly different distributions of MGUS isotype (p =0.001), lower monoclonal Ig concentration (p=0.0005), presence of an abnormal sFLC ratio (p=0.004) and distributions of Mayo Clinic risk groups (p=0.008) (see table). Conclusions. The clinical and laboratory features of AA patients with MGUS are distinctly different than in Caucasians, in particular a lower proportion of IgM MGUS, lower monoclonal Ig levels, a higher proportion of abnormal sFLC ratios, and fewer higher-risk patients. IgM MGUS is the precursor to Waldenstrom's macroglobulinemia (WM) and the lower proportion of IgM MGUS in AA is consistent with the very low rate of WM in AA. Non-IgM MGUS should be considered a separate entity and a direct comparison of AA and CA non-IgM MGUS patients using the Mayo Clinic data is planned. The significance of these differences on the risk of malignant progression will require prospective studies in racially diverse populations. Disclosures: Weiss: The Binding Site, Inc.: Research Funding.
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  • 4
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    Loss of p53 Is a Marker of Progression in Plasma Cell Neoplasias and Is a Negative Prognostic Factor in Relapsed Disease. (2008)
    American Society of Hematology
    Details
    Publication Date: 2008-11-16
    Description: Table 1. Samples to p53 deletions p 53 deletion FISH aCGH FISH and aCGH MGUS 142 - - SMM 108 - - Newly diagnosed MM - 182 - Relapsed/refractory MM 62 156 19 HMCLs - 48 - Total 312 386 19 Background: Inactivation of p53 by mutation or allelic loss is a rare event in multiple myeloma (MM) at the time of disease diagnosis and believed to be more common in the late stages of the disease. Here we defined the prevalence of p53 deletions in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed MM, relapsed MM and human myeloma cell lines (HMCLs). Indirect mechanisms of p53 inactivation such as amplification of MDM2, or deletion of CDKN2A (p14ARF) were also investigated. Patients and Methods: A total of 631 MM samples and 48 HMCLs were analyzed for p53 abnormalities (Table 1) and compared with a cohort of plasma cell leukemia (PCL) previously published by us. Interphase fluorescence in situ hybridization (FISH) and highresolution array-based comparative genomic hybridization (aCGH) were used to detect p53 deletions. MDM2 amplification and p14ARF loss were evaluated by aCGH. Overall survival (OS) was estimated through Kaplan Meier method. Results: The prevalence of p53 deletions was 1.4%, 3.7%, 8.9%, 20% and 87.5% in MGUS, SMM, newly diagnosed MM, relapsed MM and HMCLs respectively (Figure 1). Of interest patients in first relapse showed a p53 deletion prevalence of 18% in comparison with 33% for patients in second relapse or more. We obtained p53 deletion status in 8 patients noted to have deletion at the time of relapse and in whom we had previous samples stored. In 7 of 8 cases deletions had been acquired (absent in the previous samples). The median OS for relapsed MM patients with or without p53 deletion were 4.2 months and 37.8 months respectively (p
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  • 5
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    OH-2, a Hyperdiploid Myeloma Cell Line without An IGH Translocation, Has a Complex Translocation Juxtaposing MYC near MAFB and the IGK Locus (2008)
    American Society of Hematology
    Details
    Publication Date: 2008-11-16
    Description: Despite heterogeneity of phenotypes, multiple myeloma (MM) can be classified into two major groups: hyperdiploid (HRD) tumors with 48–74 chromosomes, which typically have extra copies of at least four of the eight odd chromosomes 3, 5, 7, 9, 11, 15, 19, and 21; and non-hyperdiploid (NHRD) tumors, which usually have immunoglobulin heavy chain (IGH) translocations and 74 chromosomes. Human myeloma cell lines (HMCL) with a typical HRD genotype are lacking. The OH-2 HMCL was derived from extramedullary myeloma, and retains the same HRD phenotype as the primary tumor, with extra copies of chromosomes 3, 7, 15, 19, and 21, as demonstrated by array comparative genomic hybridization. This provides a unique example of an HMCL and the corresponding primary tumor that share the same HRD phenotype. Also Spectral Karyotyping showed the same HRD phenotype. By fluorescence in situ hybridization it was shown that OH-2 does not have an IGH or Ig lambda light chain translocation. Instead, both the HMCL and the primary tumor have complex translocations involving chromosomes 2, 8, and 20. The translocation juxtaposes MAFB near MYC and the Ig kappa (IGK) enhancer. Both MYC and MAFB are highly expressed, as shown by microarray analysis, and are thought to be dysregulated by the IGK enhancer. Both OH-2 HMCL and the primary tumor cells express high levels of Cyclin D2, an expected consequence of the enhanced MAFB level. OH-2 has a phenotype similar to the 20% of HRD MM tumors that express increased levels of Cyclin D2 but not Cyclin D1 and could be a good in vitro model for studies of this subgroup of MM. OH-2 is dependent on medium containing human serum and growth-promoting cytokines like IL-6 or IL-21, reflecting the critical role of the microenvironment for growth of MM cells.
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  • 6
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    Genetic Origin of Myeloma. (2008)
    American Society of Hematology
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    Publication Date: 2008-11-16
    Description: Multiple myeloma (MM) is a tumor of isotype-switched plasma cells that accumulate in the bone marrow, replacing normal plasma cells and leading to bone destruction and marrow failure. It is often preceded by a stable monoclonal gammopathy (MG) with limited (
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  • 7
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    Identification of Three Novel Chromosomal Translocation Partners Involving the Immunoglobulin Loci in Newly Diagnosed Myeloma and Human Myeloma Cell Lines. (2005)
    American Society of Hematology
    Details
    Publication Date: 2005-11-16
    Description: Chromosomal translocations involving the immunoglobulin heavy-chain (IgH) locus at 14q32 are genetic hallmarks of human multiple myeloma (MM) and are likely primary oncogenic events in myeloma transformation. Common recurrent translocation partner genes of IgH account for 40–50% of cases and these rearrangements result in the transcriptional dysregulation of various proto-oncogenes such as CCND1, CCND3, FGFR3/MMSET, c-MAF, MAFB, MUM 1(IRF-4), c-MYC and it is becoming clear that these dysregulated genes play important roles in the pathogenesis and the treatment outcome of MM. Although the frequency of other partner genes of IgH translocations may be rare (
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  • 8
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    A Pre-Existing Plasma Cell Disorder Occurs in Most Patients with Multiple Myeloma. (2008)
    American Society of Hematology
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    Publication Date: 2008-11-16
    Description: Background. A pre-existing plasma cell disorder (PPCD), such as monoclonal gammopathy of undetermined significance (MGUS), is thought to be present in at least one-third of patients presenting with symptomatic multiple myeloma (MM). However, no study has comprehensively evaluated the proportion of patients with MM that had a PPCD by laboratory testing on pre-diagnostic sera. Methods. The Walter Reed Army Medical Center autologous stem cell transplant database was cross-referenced with the Department of Defense Serum Repository (DoDSR) database, which catalogs serum samples collected every 2 years on over 4 million active-duty service members. All samples 32 years prior to the diagnosis of MM were retrieved. Serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE) and serum free light chain analysis (sFLC) (The Binding Site, San Diego, CA) were performed on all samples. A PPCD was defined as a positive SPEP, IFE or abnormal sFLC ratio. Results. Serum samples prior to the diagnosis of MM were available for 30/90 patients, and the median number of samples per patient was 3.5 (range, 1–14). The median age at diagnosis of MM was 48.1 yrs (29–67), with 96% male, 53% Caucasian, and 47% African-American. The Ig isotype of MM was IgG 76%, IgD 10%, light-chain 7%, and non-secretory 7%. A PPCD was detected in 27/30 patients (90%, 95% CI 74–97%). The initial PPCD was detected by sFLC alone in 6/27 (22.2%), IFE alone 2/27 (7.4%), SPEP+IFE 5/27 (18.5%), SPEP+IFE+sFLC 13/27 (48.1%) and IFE+sFLC 1/27 (3.7%). There were 4 patients whose only positive sera was 2.5–3.5 years prior to diagnosis, with all preceding sera negative. Conclusions. First, a pre-existing plasma cell disorder is present in most MM patients at least 2.5 years prior to diagnosis. Second, consistent with published evidence for a small fraction of patients with high risk MGUS, 4/30 patients were documented to progress rapidly through an MGUS phase to MM. Third, 4/4 patients with light chain only or non-secretory MM had a PPCD that was detected only by sFLC, thereby indicating that all these tumors are preceded by a light chain only or non-secretory PPCD.
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