Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear run-on experiments were used to verify the hypothesis that extinction of expression of Ig synthesis in L cell x myeloma hybrids occurs at the transcriptional level. Both the H chain enhancer and promoter have been shown to be the targets for extinction in myeloma x T cell hybrids. To examine the expression of genes containing the immunoglobulin heavy chain gene (IgH) enhancer in stably transfected non-B cells, we used a vector with two selectable markers, one of which (gpt providing resistance to mycophenolic acid) either lacks an enhancer or contains the IgH enhancer, the other (neo providing resistance to G418) contains an SV40 enhancer. Stable transfectants of both myeloma (J558L) and L cells selected using G418 were tested to determine if they are also mycophenolic acid resistant. When the IgH enhancer is positioned 3' to the gpt gene, transfected J558L are mycophenolic acid resistant whereas stably transfected L-cells are mycophenolic acid sensitive. However, when large numbers of L cell transfectants are exposed to mycophenolic acid for a prolonged period, resistant subclones emerge. When the 700-bp IgH enhancer fragment was used, the majority of the subclones examined had amplified the vector, between 3 and 38 copies; when a 400-bp subfragment was used no change in the integrated genes was seen. In both cases, in the mycophenolic acid resistant subclones, increased accumulation of gpt and neo mRNA is seen. However, the gpt specific transcripts are heterogeneous in size whereas the neo transcripts are of a discrete size. The heterogeneity of the gpt transcripts results at least in part from heterogeneous initiation. When HXM-resistant L cell subclones are fused to the gamm 2b, k myeloma 4T001, extinction of Ig production occurs; therefore these cells are still capable of negatively regulating Ig expression. These results are discussed from the standpoint of both cis and trans regulatory elements and factors in non-lymphoid cells.
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PMID:Expression of genes containing the IgH enhancer in non-lymphoid cells. 211 78

The Eastern Cooperative Oncology Group evaluated hexamethylmelamine in 89 patients with advanced refractory or relapsing multiple myeloma. Hexamethylmelamine was initially used as a single agent administered orally at 200 mg/m2/day for the first 3 weeks of each 4-week cycle. When this regimen proved to be ineffective, it was modified first by increasing the dose of hexamethylmelamine to 280 mg/m2/day and subsequently by adding prednisone at 75 mg for the first 7 days of each 28-day cycle. None of the 39 patients receiving hexamethylmelamine without prednisone had an objective response, while two patients had minimal objective improvement (25%-50% decrease in M protein with symptomatic improvement). Only 14% of these patients had objective or symptomatic response or both. In contrast, patients treated with hexamethylmelamine plus prednisone had a 22% objective response rate, with another 14% showing lesser degrees of objective improvement. Fifty-one percent of the patients treated with this regimen had either objective or symptomatic improvement or both. Severe (grade 3) toxicity was seen in nearly two-thirds of the patients on the higher-dose hexamethylmelamine regimens compared with 37% of the patients receiving low-dose hexamethylmelamine; however, in most instances this represented rapidly reversible cytopenias. Because all but one of the patients responding to hexamethylmelamine plus prednisone had experienced previous treatment failure on regimens containing prednisone in similar dose and schedules, it is unlikely that the responses are due to prednisone alone. Instead, this study suggests that the activity of hexamethylmelamine in multiple myeloma is dependent on the concomitant administration of prednisone and that the combination regimen appears to be synergistic.
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PMID:Contribution of prednisone to the effectiveness of hexamethylmelamine in multiple myeloma. 311 29

Hexamethylmelamine (280 mg/m2) daily for 21 days every 28 days was given, with prednisone 75 mg on days 1-7, to patients with multiple myeloma failing to respond to, or relapsing from, previous therapy. All patients had received the same dose of prednisone in their previous treatment regimen. Among 65 evaluable patients, 35% achieved a response of some objective improvement or better. An additional 19% showed stabilization of progressive disease. Responses were achieved both in patients resistant to initial therapy and those relapsing after a response. Median survival was 10.3 months for the entire group with responding patients having significantly longer survival than nonresponders. The major toxicities are gastrointestinal and neurologic with hematologic toxicity less severe. The drug appears to have true antimyeloma tumor effect and warrants consideration for further study in combination with other agents in initial treatment.
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PMID:Hexamethylmelamine and prednisone in the treatment of refractory multiple myeloma. 680 5

Multiple myeloma (MM) is a cancer of antibody-making plasma cells. It frequently harbors alterations in DNA and chromosome copy numbers, and can be divided into two major subtypes, hyperdiploid (HMM) and non-hyperdiploid multiple myeloma (NHMM). The two subtypes have different survival prognosis, possibly due to different but converging paths to oncogenesis. Existing methods for identifying the two subtypes are fluorescence in situ hybridization (FISH) and copy number microarrays, with increased cost and sample requirements. We hypothesize that chromosome alterations have their imprint in gene expression through dosage effect. Using five MM expression datasets that have HMM status measured by FISH and copy number microarrays, we have developed and validated a K-nearest-neighbor method to classify MM into HMM and NHMM based on gene expression profiles. Classification accuracy for test datasets ranges from 0.83 to 0.88. This classification will enable researchers to study differences and commonalities of the two MM subtypes in disease biology and prognosis using expression datasets without need for additional subtype measurements. Our study also supports the advantages of using cancer specific characteristics in feature design and pooling multiple rounds of classification results to improve accuracy. We provide R source code and processed datasets at www.ChengLiLab.org/software.
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PMID:Classify hyperdiploidy status of multiple myeloma patients using gene expression profiles. 2355 30