Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Natural killer (NK) cell lymphomas are a group of rare but highly aggressive malignancies. Clinically, they can be divided into nasal NK cell lymphomas, nonnasal NK cell lymphomas, and aggressive NK cell lymphoma/leukemia. To determine the patterns of genetic deletions in these tumors, we performed loss of heterozygosity (LOH) analysis on 15 cases (11 nasal and four nonnasal), and fluorescence in situ hybridization on three cases of aggressive lymphoma/leukemia. A panel of 41 microsatellite loci on chromosomes 6q, 11q, 13q, and 17p were investigated. LOH at chromosomes 6q and 13q was frequently detected in NK cell lymphomas, being found in 80 and 66.7% of cases, respectively. LOH at chromosomes 11q and 17p was less common, being found in 28.6 and 30.8% of cases, respectively. Most tumors showed multiple loci deletions at different chromosomal regions, but several patterns of LOH could be defined. LOH at chromosome 6q was found in 90.9% of nasal NK cell lymphomas, but only in 50% of nonnasal NK cell lymphomas. LOH at chromosome 13q was found in 63.6% of nasal NK cell lymphomas and 75% of nonnasal NK cell lymphomas. For nasal NK cell lymphomas, LOH at 13q was found in 33.3% of cases at presentation, but 100% of cases at relapse. Five tumors showed LOH in only one chromosomal region, involving 6q in three cases (two nasal and one nonnasal), and 13q in two cases (both nonnasal). For the three cases of aggressive NK cell lymphoma/leukemia studied by fluorescence in situ hybridization, DNA loss at 13q14 and 17p13 regions were demonstrated. 17p13 seemed to be more commonly involved in aggressive than nasal and nonnasal NK cell lymphomas. Our results suggested that consistent patterns of LOH could be defined in NK cell malignancies. These deleted loci may contain genes important in the initiation and progression of this lymphoma.
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PMID:Consistent patterns of allelic loss in natural killer cell lymphoma. 1110 52

Patients with NHL and two or three factors of the International Prognostic Index (IPI) have a poor prognosis. We performed a prospective trial of intensive induction therapy followed with high-dose consolidation in such patients to determine the feasibility of this approach, as well as the response rate and survival. Untreated patients with aggressive lymphoma under the age of 60 with two or three adverse prognostic factors (disseminated stage, increased serum LDH, ECOG performance status >1) were prospectively included between June 1995 and April 1998 in a trial evaluating intensive induction chemotherapy with the ACE regimen (adriamycin day 1; cyclophosphamide days 1-2; etoposide days 1-3), with G-CSF support. Patients in complete remission after induction received one course of intensification with stem cell support (BEAM regimen), whereas patients in partial response received two intensifications (BEAM, then ICE regimens). Thirty-three patients (median age 38 years) were included. All patients presented WHO grade 4 leukopenia and 84% grade 3-4 thrombocytopenia during induction. There was one toxic death during induction. Twenty-nine patients proceeded to high-dose consolidation, including 12 patients who received a second high-dose treatment. The overall response rate was 88% (95% CI 76-99%), both after induction therapy and treatment completion. Thirty-nine percent of the patients had achieved complete remission after induction, and 73% after treatment completion. With a median follow-up after treatment onset of 29 months, the projected 3-year overall survival was 71% (95% CI 64-78%) and the event-free survival 58% (95% CI 50-66%). Event-free survival was significantly shorter in patients who did not achieve CR after induction therapy or after treatment completion. Early therapeutic intensification after intensive induction chemotherapy is feasible in patients with poor prognosis aggressive NHL and shows promising response and survival rates.
Leukemia 2000 Dec
PMID:A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors. 1118 6

Autologous transplantation with haematopoietic blood stem cells (ASTx) is increasingly performed in blood cell disorders, in solid tumours and recently, in severe autoimmune disorders. In acute leukaemia, ASTx is usually offered to patients in complete remission who lack an HLA-identical donor. The chances and risks must be weighed against a transplant from a matched, unrelated donor. ASTx are routinely performed in aggressive lymphoma. Indications for ASTx in intermediate and low grade lymphoma await results of clinical trials. In Hodgkin's disease and myeloma, ASTx are routinely performed in first or subsequent remission, and in early stages, respectively. Among solid cancers, ASTx is an established part of the therapeutic measures in germ cell tumours. Patients with breast cancer may undergo ASTx in an adjuvant setting after complete tumour resection or in a palliative setting after progression. Initial enthusiasm has switched to a more awaiting view of this indication. Severe autoimmune disorders may undergo haemolymphatic ablation from conditioning and a stem cell transplant. The scientific evaluation of this approach should employ three sequential steps: The first step should employ vigorous immunosuppression followed by ASTx; the second step should employ stem cell autografts depleted from autoreactive immune cells; the third step should employ allogeneic stem cells from normal donors. A truly curative approach after complete haemolymphatic reconstitution is conceivable.
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PMID:[Autologous transplantation of hematopoietic stem cells--therapeutic spectrum and future developments]. 1126 Dec 70

Chronic lymphocytic leukaemia (CLL) is a disease of late middle age and older. The majority of patients are diagnosed because of a lymphocytosis of at least 5 x 10(9)/L on an incidental blood count. It needs to be distinguished from mantle cell lymphoma and splenic marginal zone lymphoma by lymphocyte markers. The immunophenotype of CLL is sparse surface immunoglobulin, CD5+, CD19+, CD23+, CD79b-, and FMC7-. The disease is staged according to the presence of lymphadenopathy and/or splenomegaly and the features of bone marrow suppression. Most patients have an early stage of disease when diagnosed and perhaps 50% will never progress. This group of patients have a normal life expectancy and do not require treatment beyond reassurance. Progression involves an increasing white cell count, enlarging lymph nodes and spleen, anaemia and thrombocytopenia. Complications of progression include autoimmune haemolytic anaemia and thrombocytopenia, immunodeficiency, and the development of a more aggressive lymphoma. A range of prognostic factors is available to predict progression, but most haematologists rely on close observation of the patient. Intermittent chlorambucil remains the first choice treatment for the majority of patients. Combination chemotherapy offers no advantage. Intravenous fludarabine is probably more effective than chlorambucil, but no trial has yet shown a survival advantage for using it first rather than as a salvage treatment in patients not responding to chlorambucil. It is at least 40 times as expensive as chlorambucil. Cladribine may be as effective as fludarabine, although it has been used less and is even more expensive. Patients who relapse after chlorambucil should be offered retreatment with the same agent and if refractory should be switched to fludarabine, which may also be offered for retreatment on relapse. For patients refractory to both drugs, a variety of options are available. High dose corticosteroids, high dose chlorambucil, CHOP (cyclophosphamide, prednisolone, vincristine and doxorubicin), anti-CD52, anti-CD20 and a range of experimental drugs which are being evaluated in clinical trials. Younger patients should be offered the chance of treatment with curative intent, preferably in the context of a clinical trial. Autologous stem cell transplantation after achieving a remission with fludarabine has relative safety and may produce molecular complete remissions. Only time will tell whether some of these patients are cured but it seems unlikely. Standard allogeneic bone marrow transplant is probably too hazardous for most patients, but non-myeloablative regimens hold out the hope of invoking a graft-versus-leukaemia effect without a high tumour-related mortality. Trials of immunotherapy are exciting options for a few patients in specialised centres.
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PMID:Achieving optimal outcomes in chronic lymphocytic leukaemia. 1136 85

Standard chemotherapy has been ineffective for improving the poor 10-year survival rate of patients with indolent lymphoma. However, a wider choice of therapeutic modalities has become recently available, including immunotherapy with monoclonal antibodies and allogeneic peripheral blood stem cell transplantation. Accordingly, a sensitive prognostic indicator is required to identify high-risk patients and to help design new therapeutic approaches for them. We previously reported that the serum nm23-H1 protein level was an independent prognostic factor for aggressive lymphoma. The present study was performed to assess the clinical implications of this protein on indolent lymphoma and whether it can be used to classify the aggressiveness of the disease in order to assist in the individualization of therapy. A total of 130 patients with indolent lymphoma were enrolled in this multicenter study. The serum nm23-H1 protein level was significantly higher in patients with indolent lymphoma than in a normal control group. In addition, indolent lymphoma patients with higher nm23-H1 levels had worse overall and progression-free survival rate than those with lower nm23-H1 levels. Therefore, nm23-H1 in serum may be useful for identifying a distinct group of patients at high risk.
Leukemia 2001 May
PMID:Serum nm23-H1 protein as a prognostic factor for indolent non-Hodgkin's lymphoma. 1136 46

To investigate the lymphomagenesis of NK/T lymphoma, we comprehensively and systematically analyzed the expression pattern of the human NK/T cell line (NK-YS) genome by cDNA expression array and tissue microarray. We detected significant changes in the gene expression of NK-YS cell line: an increase in 18 and a decrease in 20 genes compared to normal NK cells or peripheral blood mononuclear cells. Among these genes, we found a strong decrease in hematopoietic cell specific protein-tyrosine-phosphatase SH-PTP1 (SHP1) mRNA by cDNA expression array and reverse transcriptase-polymerase chain reaction. Further analysis with standard immunohistochemistry and tissue microarray, which used 207 paraffin-embedded specimens of various kinds of malignant lymphomas, showed that 100% of NK/T lymphoma specimens and more than 95% of various types of malignant lymphoma were negative for SHP1 protein expression. On the other hand, SHP1 protein was strongly expressed in the mantle zone and interfollicular zone lymphocytes in reactive lymphoid hyperplasia specimens. In addition, various kinds of hematopoietic cell lines, particularly the highly aggressive lymphoma/leukemia lines, lacked SHP1 expression in vitro, suggesting that loss of SHP1 expression may be related to not only malignant transformation, but also tumor cell aggressiveness. SHP1 expression could not be induced in either of two NK/T cell lines by phorbol ester, suggesting that genetic impairment or modification with methylation of SHP1 DNA could be one of the critical events in the pathogenesis of NK/T lymphoma. This evidence strongly suggests that loss of SHP1 gene expression plays an important role in multistep tumorigenesis, possibly as an anti-oncogene in the wide range of lymphomas/leukemias as well as NK/T lymphomas.
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PMID:Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias : combination analysis with cDNA expression array and tissue microarray. 1158 76

We have previously shown that ICAM-1-deficient mice were resistant to lymphoma dissemination of intravenously injected 164T2 lymphoma cells. Highly aggressive variants of this cell line, however, could overcome this resistance. To discern the complex pattern of gene expression involved in the evolution of aggressiveness in lymphoma cells, we compared the transcriptome of 164T2 cells with that of their aggressive variants using cDNA arrays. We identified several genes that were differentially expressed in nonmetastatic lymphoma cells and their metastatic variants. Galectin-7, associated with the development of chemically induced mammary carcinoma, was one such gene whose expression was significantly upregulated. We showed that it was constitutively expressed in aggressive variants, at both mRNA and protein levels. Galectin-7 expression in aggressive lymphoma cells was induced upon in vivo selection in several organs, including the thymus, the spleen and kidneys. We also showed that treatment of nonaggressive lymphoma cells with 5-aza-2'-deoxycytidine was sufficient to induce galectin-7 gene expression. This report is the first to show that galectin-7 is expressed in aggressive lymphoma.
Leukemia 2003 Apr
PMID:Upregulation of galectin-7 in murine lymphoma cells is associated with progression toward an aggressive phenotype. 1268 33

HMG-I/Y is overexpressed in human cancer, although a direct role for this gene in transformation has not been established. We generated transgenic mice with HMG-I targeted to lymphoid cells. All seven informative founder HMG-I mice developed aggressive lymphoma by a mean age of 4.8 months. Tumors express T-cell markers and are transplantable. We also demonstrate that HMG-I mRNA and protein are increased in human acute lymphocytic leukemia samples. Our results show that HMG-I functions as an oncogene and suggest that it contributes to the pathogenesis of leukemia and other cancers with increased HMG-I expression.
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PMID:The HMG-I oncogene causes highly penetrant, aggressive lymphoid malignancy in transgenic mice and is overexpressed in human leukemia. 1515 86

Adjuvant combination chemotherapy reduces the risk of relapse and death for patients with invasive breast cancer and adds to the benefits obtained with hormonal treatment. Generally, anthracycline-containing regimens are superior to non-anthracycline regimens, treatments longer than 6 months are not advantageous and high-dose chemotherapy regimens, which require autologous hematopoietic stem cell support, have not proved consistently superior. The development and evaluation of the taxanes was highly anticipated as they have shown high levels of efficacy while appearing to be non-cross-resistant with partially non-overlapping toxicities. A role for taxanes in the adjuvant or neoadjuvant setting is now widely acknowledged, although they are not currently approved for treatment of early breast cancer in Europe. In patients with aggressive lymphoma who receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, 40% to 70% of patients attain a complete remission, depending on risk factors such as age and extranodal involvement. Second- and third-generation regimens like m-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide), Pro-MACE-CytaBOM (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate), and MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) have largely failed to improve treatment outcome. The use of monoclonal anti-CD20 antibodies or dose escalation have shown promising results in improving relapse-free and survival rates. In patients with breast cancer, the key Cancer and Leukemia Group B 9741 trial showed that dose-dense doxorubicin, cyclophosphamide, and paclitaxel chemotherapy with granulocyte colony-stimulating factor (G-CSF), repeated every 2 weeks, is superior to the same regimen administered at standard 3-weekly intervals. In lymphoma, dose-dense CHOP chemotherapy has shown superiority over standard CHOP regimens, particularly in elderly patients with aggressive non-Hodgkin's lymphoma. G-CSF factor is essential to enable the administration of dose-dense chemotherapy and any reduction in its use leads to significant increases in infectious complications. Current evidence suggests that dose-dense chemotherapy, enabled by G-CSF, is an important breakthrough in the evolution of chemotherapy for breast cancer and lymphoma.
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PMID:Dose-dense chemotherapy in breast cancer and lymphoma. 1518 5

Second malignancies are frequent complications in patients with chronic lymphocytic leukemia (CLL). Patients with this leukemia may develop large cell lymphoma (LCL) known as Richter's syndrome (RS). RS occurs in CLL patients of about 3% and may develop in a single lymph node or more often in a group of nodes. However, in some patients extranodal localization of aggressive lymphoma in RS has been observed. Besides LCL, Hodgkin's disease, prolymphocytoid leukemia, multiple myeloma and acute lymphoblastic leukemia may also occur as RS variants. The origin of lymphoid cells in RS remains tentative. However, CLL and RS originate from the same clone for some patients, whereas, in other patients cells of aggressive lymphoma do not have the features of the same clone as the CLL cells. The prognosis of RS is poor. Survival in different studies will be usually 2-5 months. The secondary development or coexistence of myeloproliferative disorders or myelodysplastic syndrome and solid tumors have also been rarely documented in CLL patients. It is of great concern that therapy may further increase the risk of a second neoplasm. However, until now, there are no clear evidence that alkylating agents or purine nucleoside analogs may be associated with an increased incidence of second malignancies in patients with CLL. In this review, epidemiology, biology, clinical characteristic and treatment approaches in RS and other secondary neoplasms in patients with CLL are discussed.
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PMID:Second malignancies and Richter's syndrome in patients with chronic lymphocytic leukemia. 1576 79


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