Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methylglyoxalbisguanylhydrazone or MGBG is an agent with a unique mechanism of action (polyamine biosynthesis inhibition). MGBG was discarded in the 1960s because of severe mucositis and other toxicities. New clinical trials in the late 1970s and early 1980s utilized weekly administration and indicated MGBG had significant activity in patients with chemotherapy-refractory Hodgkin's and non-Hodgkin's lymphoma. In addition, some activity was noted in patients with head and neck, prostate, esophageal, and endometrial cancer. The toxicities on the weekly schedule were minimal and no myelosuppression was noted. Based on MGBG's spectrum of antitumor activity and its activity in severely debilitated patients, we hypothesize that MGBG may have greater antitumor activity in patients who are malnourished (possibly based on polyamine depletion). MGBG is a good candidate for treatment of AIDS-associated NHL because it has proven activity in patients with NHL which is not associated with AIDS, crosses the blood brain barrier, is non-myelosuppressive, and appears to work in patients with inanition (no polyamines available to reverse MGBG's antitumor effects). Clinical trials are ongoing to determine the activity of MGBG in AIDS-associated NHL and other diseases. Based on encouraging initial results, it appears MGBG may become part of our therapeutic armamentarium.
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PMID:MGBG: teaching an old drug new tricks. 791 20

Lymphoreticular neoplasms of the larynx are rare and comprise a heterogeneous group of tumors. A systematic survey of the literature and autoptic evaluation of the larynx in a relatively small number of patients with systemic lymphoreticular malignancies yielded the following findings: Primary tumors of the larynx must be clearly distinguished from laryngeal involvement by systemic or leukemic infiltrations. By far the most common primary hemopoietic tumors of the larynx are extramedullary plasmacytoma (about 90 cases published) and non-Hodgkin's lymphoma (NHL; about 65 cases published). Primary Hodgkin's disease, granulocytic sarcoma and mast cell sarcoma are extremely rare at this site. Plasmacytoma and NHL both preferentially involve the supraglottis. The subglottis is infrequently affected. Laryngeal plasmacytoma and NHL usually present clinically as localized stage IE and IIE tumors that exhibit no significant tendency to recur or generalize. The therapy of choice is local irradiation while chemotherapy should be reserved for recurrent or progressive disease. Prognosis is favourable in most cases of primary laryngeal plasmacytoma and NHL. Secondary involvement of the larynx by systemic lesions or leukemic infiltrations is usually associated with a very poor prognosis. The prognosis of patients with laryngeal involvement in acute or chronic myeloid leukemia is always poor. Although the histopathological diagnoses given in many case reports are often difficult to compare because of differences in terminology, there seems to be a marked preponderance of B-cell tumors of high-grade malignancy (centroblastic or immunoblastic lymphoma in the Kiel classification of NHL) that probably represents lymphomas originating from mucosa-associated lymphoid tissue (MALT).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The larynx in lymphoproliferative and myeloproliferative diseases. Part II: Laryngeal autopsy findings and discussion]. 792 29

A B-cell non-Hodgkin's lymphoma (B-NHL) cell line (Karpas 1106) with an unusual three-way translocation involving 18q21.3 has been derived from a patient with mediastinal lymphoblastic B-NHL. Although conventional cytogenetics showed a derivative 18q-identical to that seen in cases with t(14;18)(q32.3;q21.3), no translocations of either chromosome 14 could be detected. Instead fluorescent in situ hybridization analysis using a chromosome-18 paint showed that the segment 18q21.3-18qter had become sandwiched on a derivative chromosome X between segments Xqter-c-Xq28 and 13q12-qter, with the centrometric site of 18q21.3 subband juxtaposed to the X sequences. Pulsed-field DNA blots failed to detect rearrangement of the BCL2 gene. Conventional DNA blots using a variety of restriction digests and both 5' and 3' BCL2 and FVT 1 probes also failed to detect rearrangement in Karpas 1106. A rearranged fragment seen only in HindIII digests with 5' BLC2 probes may represent a local microalteration, which is either a mutation or small deletion involving the HindIII site as seen in other cases of B-NHL. Neither BCL2 RNA nor BCL2 protein expression were detected. These and other data suggest that genes at 18q21.3, other than BCL2 and FVT1, may be targets for translocation in certain subgroups of B-NHL.
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PMID:B-cell non-Hodgkin's lymphoma cell line (Karpas 1106) with complex translocation involving 18q21.3 but lacking BCL2 rearrangement and expression. 794 96

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.
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PMID:WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. 794 79

The expression of the murine double minute-2 (MDM2) gene, the product of which binds to and inactivates p53, was studied in 60 patients with B-cell chronic lymphocytic leukemia (B-CLL) or non-Hodgkin's lymphoma (B-NHL). Northern blot analysis showed that the level of MDM2 gene expression was low in normal human B-cells, whereas 17 of the patients (28.3%) with B-CLL or NHL had more than 10-fold higher levels of MDM2 gene expression than that observed in normal B cells. Immunohistochemical analysis confirmed MDM2 overexpression at the cellular protein level. MDM2 gene overexpression was found more frequently in patients with the low-grade type of lymphoma (56.5%) than in those with intermediate-/high-grade types (10.8%) (P = .001). Moreover, MDM2 overexpression was found significantly more frequently in patients at advanced clinical stages. Simultaneous analysis of p53 gene mutation showed that three patients had both MDM2 gene overexpression and p53 gene mutation. The results of the present study suggest that MDM2 gene overexpression may play an important role in the tumorigenicity and/or disease progression of CLL and low-grade lymphomas of B-cell origin.
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PMID:The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin. 794 88

Gastrointestinal (GI) disease is frequent in all types of immunocompromised patients but occurs with greatest frequency in patients with acquired immunodeficiency syndrome (AIDS). Thus, much of this review deals with human immunodeficiency virus (HIV)-related GI diseases. Gastrointestinal diseases in other immunocompromised patients are compared with those in patients with AIDS. Conditions unique to transplant recipients, such as graft-versus-host disease (GVHD) and posttransplant lymphoproliferative disorders (PTLDs), are discussed separately. We have divided these GI diseases into four main categories: (1) HIV-related inflammatory conditions other than opportunistic infections (HIV-related enteropathy, proctocolitis, and CD8 lymphocytosis); (2) inflammatory conditions unrelated to HIV or opportunistic infections (neutropenic enterocolitis, regional enteritislike enteropathy, and GVHD); (3) opportunistic infections (illnesses caused by herpesvirus, cytomegalovirus, and miscellaneous other viruses; Mycobacterium, Candida, Histoplasma, Cryptococcus, Cryptosporidium, Microsporida, Isospora, Leishmania, Toxoplasma and Strongyloides organisms as well as Pneumocystitis carinii; and (4) neoplasias (Kaposi's sarcoma [KS], AIDS-related non-Hodgkin's lymphoma [NHL], HIV-related Hodgkin's disease [HD], PTLDs, and miscellaneous neoplasms). The prevalence, pathogenesis, clinical manifestations, gross pathological findings, and microscopic features of each disease entity are discussed.
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PMID:Gastrointestinal disease in the immunocompromised patient. 795 57

A high frequency of lymphoma in human immunodeficiency virus-infected individuals has been reported since the outbreak of the acquired immunodeficiency syndrome (AIDS) epidemic in 1982. AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) is almost invariably derived from B cells and is classified as high- or intermediate-grade NHL, according to the working formulation. Two main histologic types are recognized, including small noncleaved cell lymphoma (SNCCL) and diffuse large cell lymphoma (DLCL). Pre-existing host factors putatively involved in lymphoma development include disrupted immunosurveillance, deregulated cytokine production, chronic antigen stimulation, and infection by Epstein-Barr virus (EBV). These alterations are associated with the development of multiple oligoclonal expansions which correspond to the clinical phase known as persistent generalized lymphadenopathy (PGL). The appearance of a true AIDS-NHL is characterized by the presence of a monoclonal B-cell population displaying several genetic lesions, including monoclonal EBV infection, c-MYC and BCL-6 rearrangements, RAS mutations, p53 inactivation, and 6q deletions. These genetic lesions cluster into two distinct molecular pathways, which specifically associate with the different histologic subtypes of AIDS-NHL, i.e., AIDS-SNCCL and AIDS-DLCL. The presence of distinct genetic pathways for AIDS-SNCCL and AIDS-DLCL correlate with a number of clinical features which distinguish these two groups of tumors, including differences in the age of onset, CD4 counts at the time of presentation, time elapsed since HIV infection, and clinical outcome.
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PMID:Molecular pathology of AIDS-related lymphomas. Biologic aspects and clinicopathologic heterogeneity. 799 35

Primary extranodal non-Hodgkin's lymphoma (p-EN-NHL) of the kidneys with acute renal failure as the only manifestation is very rare. The origin of neoplastic lymphoid cells in the kidneys, organs normally free of lymphoid tissue, is an unsolved problem. A literature review over the last ten years revealed only 9 adult cases, including ours that match the usual criteria: (1) renal failure as the initial presentation, (2) bilateral enlargement of the kidneys without obstruction and other organ or nodal involvement, (3) diagnosis only made by renal biopsy, (4) absence of other causes of renal failure, and (5) rapid improvement of renal function after radiotherapy or, as in our case, systemic chemotherapy. Autopsy on two patients confirmed that p-EN-NHL of the kidneys without dissemination does exist as a separate entity.
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PMID:Acute renal failure due to bilateral lymphomatous infiltrates. Primary extranodal non-Hodgkin's lymphoma (p-EN-NHL) of the kidneys: does it really exist? 799 34

A phenotypic and molecular evaluation was made of 15 patients with mature B-cell leukemia/lymphoma showing exclusive spleen and bone marrow involvement. According to French-American-British criteria, these cases could not be classified as classical B-cell chronic lymphocytic leukemia, hairy cell leukemia and its variant forms, splenic lymphoma with villous lymphocytes, or leukemic phase non-Hodgkin's lymphoma (NHL; follicular or intermediate type). The immunophenotype pattern (high surface Ig and CD25 expression, and little or no reactivity with CD5, CD23, and CD11c) and cytomorphologic features of these neoplasms suggested an origin in the marginal zone of the spleen. Molecular analysis did not show any involvement of the dominantly acting oncogenes generally associated with lymphoid malignancies (c-myc, bcl-2, bcl-1, Ras), but mutations of the p53 tumor suppressor gene involving exons 5, 6, and 8 were found in 6 cases (6 of 15, 40%). In 4 cases, the p53 alterations consisted of a point mutation leading to amino acid substitution. In the remaining 2 cases, an insertion or deletion resulting in a frame-shift of the protein was observed. In all but 1 of the cases, the wild-type sequence at the mutation site was barely visible, implying the loss of the normal p53 allele in leukemic cells. All of the cases showed a clinical course compatible with that of low-grade NHL, regardless of the p53 loss/mutation. Overall, our data suggest the existence of a form of splenic B-cell leukemia/lymphoma of possible marginal zone origin in which p53 inactivation may play an important pathogenetic role.
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PMID:Frequent p53 gene involvement in splenic B-cell leukemia/lymphomas of possible marginal zone origin. 801 22

The structures of rearranged gamma-chain T-cell antigen receptor (TCR) genes were analyzed in 5 cases of T-cell acute lymphoblastic leukemia (T-ALL), in 15 cases of peripheral T-cell non-Hodgkin's lymphoma (T-NHL), in 1 case with large granular CD8 lymphocytosis, 1 case with CD8 lymphocytosis after autologous bone marrow transplantation for Hodgkin's disease, and in 2 cases with nonneoplastic diseases. Rearranged V-J TCR gamma-gene segments were amplified by the polymerase chain reaction (PCR). Because most of the biopsy tissue or bone marrow samples contained significant amounts of admixed nonmalignant T-cells, direct DNA sequencing of the PCR products yielded mixed sequence data because of coamplification of clonal together with polyclonal TCR gamma V-N-J junctions. Reliable data could only be obtained by cloning the V gamma-J gamma PCR products and sequencing several (4 to 10) randomly chosen clones. In the polyclonal samples, all PCR-derived clones differed in their specific V-N-J junctions, as expected. In the two T-cell lines and in most of the T-cell malignancies, monoclonal PCR products could be identified by the demonstration of clonally restricted V-N-J junctions. In most cases, this information yielded the desired clone-specific sequence and showed a background population of polyclonal TCR gamma cells in each specimen, except for those that were obtained from the T-ALL samples, the cell lines, or the NHL samples with high tumor cell fraction. The results obtained by PCR-directed sequencing were confirmed by temperature-gradient gel electrophoresis (TGGE) that showed distinct DNA bands only with the PCR products containing predominant (ie, monoclonal) TCR gamma V-N-J junctions. By combined sequence and TGGE analysis, it was found that PCR/TGGE is able to distinguish between monoclonal and polyclonal TCR gamma-PCR products. This finding prompted us to complete the analysis of the TCR gamma locus in the samples by PCR/TGGE using primer mixes which covered all possible V gamma and J gamma recombinations. Monoclonality was shown with all mixes by PCR/TGGE in 21 of 24 (87%) of the lymphoproliferations. In summary, the present study shows that the combination of amplifying TCR gamma V-N-J junctions by PCR with the identification of clonal PCR products by TGGE and DNA sequencing is a reliable method for the characterization of clonal TCR gamma sequences.
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PMID:Characterization of clone-specific rearrangement T-cell receptor gamma-chain genes in lymphomas and leukemias by the polymerase chain reaction and DNA sequencing. 802 83


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