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

There appear to be four primary areas of interest in the application of cytogenetic techniques to the study of malignant lymphomas: (1) the role of cytogenetics in the diagnosis of lymphoma in problem cases, (2) as an aid to the classification of malignant lymphomas, (3) whether specific chromosomal patterns will have prognostic significance for response to therapy or survival, and (4) the role of cytogenetics in staging of malignant lymphomas. A case of reactive lymphoid hyperplasia is reported in which cytogenetic studies demonstrated an aneuploid clone suggesting that cytogenetic abnormalities of lymphoma may precede the diagnostic histopathologic picture. The occurrence of 14q+ marker chromosomes in plasmacytic myeloma, plasma cell leukemia, malignant lymphomas, Burkitt's lymphoma, and ataxia-telangiectasia suggest that a common etiologic or pathogenetic mechanism may be present in some of these disorders. A preliminary pilot study of spleens removed at staging laparotomy for Hdgkin's disease suggests that cytogenetic studies may be able to detect Hodgkin's disease that is not apparent histologically. Further studies are required to provide answers to these areas of interest in cytogenetics in malignant lymphoma.
 ...
PMID:Cytogenetics in malignant lymphoma. 10 1

The association between cancer and immunodeficiency is well established. In common variable immunodeficiency (CVI), a primary immunodeficiency disease characterized by low serum immunoglobulins and poor antibody production, we previously reported a total of 13 cancers in 11 individuals arising in continuously observed group of patients. Of the 13, 7 were NHL and 1 was a myeloma which progressed to lymphoma. We report here the histologic, immunologic, cytogenetic, and clinical features of these 8 NHL along with 3 new lymphomas which have appeared in this group (now 117 patients). From our studies, the lymphomas which have arisen in CVI share certain features with the lymphomas which appear in the childhood immunodeficient syndromes. Wiskott Aldrich Syndrome, Ataxia Telangiectasia, or severe combined immunodeficiency: they are similar in overall frequency (13%), are often B-cell in origin, and extranodal in location. However, unlike the lymphomas of the immunodeficient child, lymphomas in CVI may be more differentiated and secrete immunoglobulin. For CVI patients with stage I or II disease, as for non-Hodgkin lymphomas in general, the prognosis is good. In our group, NHL in CVI have appeared most often in females of the 5th to 7th decade and not in childhood. Cytogenetic studies in lymphomas show that cytogenic abnormalities, including chromosomal translocation, can be found in this group, but more studies will be needed to assess the frequency of these events.
 ...
PMID:Non-Hodgkin lymphoma in common variable immunodeficiency. 182 73

A total of 734 serum specimens from various clinical disorders along with 100 control samples from healthy subjects were processed for estimation of serum IgG, IgA and IgM employing single radial immunodiffusion procedure. Immunoglobulin deficiency, either selective or combined was noted in 31 males and 24 females in all age groups. Of the 55 cases encountered it was secondary immunoglobulin deficiency which was seen on a larger scale and encountered in patients with Multiple myeloma (16 out of 32) followed by Leprosy (14 out of 250), Lymphoma (5 out of 43), Malaria (4 out of 137), Burns (4 out of 52), Rheumatoid arthritis (2 out of 69) and non lymphoreticular malignancies (1 out of 41) in decreasing order of frequency. Primary immunoglobulin deficiency was observed in nine cases comprising of six belonging to Idiopathic late onset immunoglobulin deficiency, two of dysgammaglobulineamia and a solitary case of Ataxia telangiectasia. Panimmunoglobulin deficiency was observed in six cases, 11 had a dual deficiency while 38 showed deficiency of an isolated class with selective IgA deficiency in 20 cases. Furthermore, one patient each had total absence of IgG or IgA while IgM was not detectable in seven patients. A high suspicion index along with a regular rapport between the clinician and the laboratory personnel is necessary in the diagnostic set up of immunoglobulin deficiency states.
 ...
PMID:Analysis of immunoglobulin deficiency cases: a five year study. 935 99

Cytogenetic analysis of small lymphocytes disorders is hindered by the low mitotic activity of the malignant cells. The use of fluorescence in situ hybridization (FISH) allows the detection of chromosomal amplifications, deletions, or translocations at a single-cell level in dividing and resting cells. The use of FISH in combination with other molecular techniques has defined the deletion in band 13q14 as the most common abnormality in chronic lymphocytic leukemia, followed by del (11)(q22-23), trisomy 12, del (17)(p13), and del (6)(q21). The del 13q14 is also found in 70% of mantle-cell lymphomas (MCLs) and in non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukemia (ALL), and multiple myeloma (MM) patients. These findings point to the existence of yet unidentified tumor-suppressor gene(s) at the 13q14 locus, the loss/inactivation of which leads to B-cell neoplasia. Del (17(p13) (involving the p53 tumor-suppressor gene) and del (11)(q22-23) (involving the ataxia-telangiectasia gene [ATM]) seem to be independent prognostic factors for poor survival in chronic lymphocytic leukemia (CLL) patients. In MCL, the t(11;14) involving the bcl-1 gene is found, but data from a bcl-1 transgenic animal model suggest that hyperexpression of bcl-1 is not sufficient for lymphomatogenesis. Similar data are observed in bcl-2 transgenic animals, a finding showing that the bcl-2 hyperexpression observed in t(14;18)-positive follicular lymphoma cells is not sufficient to confer a malignant phenotype. The contribution of other chromosomal abnormalities other than bcl-1 and bcl-2 rearrangements in the pathogenesis of MCL and follicular-cell lymphomas has to be determined.
 ...
PMID:Genetics of small lymphocyte disorders. 1031 86

Deletions of 13q14.3 are well known in several malignancies and are thought to be associated with tumour suppressor function. The RB-1 gene is a tumour suppressor gene, but other loci including D13S319 and D13S25 telomeric to this within 13q14.3 are deleted in B-cell chronic lymphocytic leukaemia (B-CLL), multiple myeloma and non-Hodgkin's lymphoma, with varying clinical significance. The fluorescence in situ hybridization screening of 22 patients with T-prolymphocytic leukaemia (T-PLL) for deletions of 13q14.3 revealed loss of D13S25 in 17 cases (mean 40% range 13-98%), with 11 patients having at least a 20% deletion. Mapping the deletions for the RB-1, D13S319,and D13S25 loci revealed D13S25 as the most frequently deleted marker. However, patients with only the D13S25 deletion had low percentages of cells with the deletion (12-13%), suggesting that loss of D13S25 on its own may not provide sufficient growth advantage. The use of the YAC 954c12, which maps immediately adjacent to D13S25, defined the telomeric border of the deletion in some of the cases. Inv(14)(q11q32) and t(14;14)(q11;q32) are characteristic of T-PLL, but are also observed in premalignant T-cell clones in patients with ataxia telangiectasia. Transition to overt leukaemia may result from loss of suppressor function. Thus, 13q14.3 deletions could contribute to the development of overt leukaemia in T-PLL, but the involvement of more than one gene in the region cannot be excluded.
 ...
PMID:Deletions of D13S25, D13S319 and RB-1 mapping to 13q14.3 in T-cell prolymphocytic leukaemia. 1152 51

We have recently shown that proteasome inhibitor PS-341 induces apoptosis in drug-resistant multiple myeloma (MM) cells, inhibits binding of MM cells in the bone marrow microenvironment, and inhibits cytokines mediating MM cell growth, survival, drug resistance, and migration in vitro. PS-341 also inhibits human MM cell growth and prolongs survival in a SCID mouse model. Importantly, PS-341 has achieved remarkable clinical responses in patients with refractory relapsed MM. We here demonstrate molecular mechanisms whereby PS-341 mediates anti-MM activity by inducing p53 and MDM2 protein expression; inducing the phosphorylation (Ser15) of p53 protein; activating c-Jun NH(2)-terminal kinase (JNK), caspase-8, and caspase-3; and cleaving the DNA protein kinase catalytic subunit, ATM, and MDM2. Inhibition of JNK activity abrogates PS-341-induced MM cell death. These studies identify molecular targets of PS-341 and provide the rationale for the development of second-generation, more targeted therapies.
 ...
PMID:Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. 1239

Specific genetic abnormalities are of prognostic significance for patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM); however, routine cytogenetic analysis usually provides normal results. We utilized two probe panels for interphase fluorescence in situ hybridization (FISH) studies to enhance the ability to detect genetic abnormalities in samples that were referred for routine cytogenetic studies for possible diagnoses of CLL or MM. The CLL panel consisted of probes for 11q22.3 (ATM gene), 13q14 (D13S319), the centromere of chromosome 12 (D12Z3) and 17p13.1 (P53 gene). The MM panel included probes for 14q32 (IgH gene) and/or t(11:14)(q13;q32) (BCL1/IgH), 13q14 (D13S319) and 17p13.1 (P53 gene). FISH detected clonal aberrations not identified by conventional cytogenetics in an additional 8 of 23 (35%) samples referred for possible CLL and 7 of 42 (17%) samples with possible MM. The prognostic significance of the aberrations identified ranged from favorable, to intermediate, to poor. Our studies indicate that many samples referred for routine cytogenetics testing for CLL and MM yield normal results for both conventional and FISH testing, likely due to lack of definitive diagnosis in a percentage of cases. However, FISH is more sensitive for the detection of clinically significant chromosome abnormalities and should be the testing methodology of choice for these disorders.
 ...
PMID:Utility of Interphase FISH Panels for Routine Clinical Cytogenetic Evaluation of Chronic Lymphocytic Leukemia and Multiple Myeloma. 1534 87

Red wine polyphenol, trans-resveratrol (trans-3,4',5-trihydroxy stilbene), has potent chemopreventive effects against various tumors. In this study, we found for the first time that resveratrol rapidly induces S phase cell cycle arrest of human malignant B cells including myeloma cells in dose- and time-dependent manners, followed by S phase cell cycle arrest through ATM/Chk pathway. Resveratrol-induced apoptosis occurs in association with the activation of caspase-3 and the loss of mitochondrial transmembrane potentials. In addition, resveratrol induces the phosphorylation of p38 MAP kinase, and specific inhibition of p38 MAP kinase abolishes the resveratrol-induced apoptosis, indicating that activation of the p38 MAP kinase pathway is required for inducing apoptosis in malignant B cells. These results suggest that resveratrol may have potential as a novel therapeutic agent for the patients with B cell malignancies including multiple myeloma.
 ...
PMID:Resveratrol induces apoptosis of human malignant B cells by activation of caspase-3 and p38 MAP kinase pathways. 1642 27

Proteasome inhibitors are novel antitumor agents against multiple myeloma and other malignancies. Despite the increasing clinical application, the molecular basis of their antitumor effect has been poorly understood due to the involvement of the ubiquitin-proteasome pathway in multiple cellular metabolisms. Here, we show that treatment of cells with proteasome inhibitors has no significant effect on nonhomologous end joining but suppresses homologous recombination (HR), which plays a key role in DNA double-strand break (DSB) repair. In this study, we treat human cells with proteasome inhibitors and show that the inhibition of the proteasome reduces the efficiency of HR-dependent repair of an artificial HR substrate. We further show that inhibition of the proteasome interferes with the activation of Rad51, a key factor for HR, although it does not affect the activation of ATM, gammaH2AX, or Mre11. These data show that the proteasome-mediated destruction is required for the promotion of HR at an early step. We suggest that the defect in HR-mediated DNA repair caused by proteasome inhibitors contributes to antitumor effect, as HR plays an essential role in cellular proliferation. Moreover, because HR plays key roles in the repair of DSBs caused by chemotherapeutic agents such as cisplatin and by radiotherapy, proteasome inhibitors may enhance the efficacy of these treatments through the suppression of HR-mediated DNA repair pathways.
 ...
PMID:Inhibitors of the proteasome suppress homologous DNA recombination in mammalian cells. 1787 93

Ataxia Telangiectasia (A-T) patients have biallelic inactivation of the ATM gene and exhibit a 200-fold-increased frequency of lymphoid tumours. ATM mutations have been found in a number of adult lymphoid malignancies but there is no data on the occurrence of ATM mutations in multiple myeloma tumours. The purpose of our work was to investigate the occurrence of ATM mutations in multiple myeloma and to this end we screened 45 sporadic cases for ATM mutations using denaturing high-performance liquid chromatography analysis and DNA sequencing. Pathogenic ATM mutations were identified in 2/45 of the myelomas compared with a published estimate of ATM mutant allele frequency in the UK population of 2/521 (P = 0.033). One was the missense mutation 7181C>T which was then modelled in an expression system and the S2394L protein shown to have no ATM kinase activity. The second myeloma had the pathogenic ATM splice site mutation IVS40-1G>C leading to loss of exon 41. We also report a 48-year-old ataxia telangiectasia patient who developed multiple myeloma. Taken together our study suggests that ATM mutation may play a role in the pathogenesis of a subset of multiple myelomas.
 ...
PMID:Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patients. 1857 9


1 2 3 4 5 Next >>