Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human myeloid cell nuclear differentiation antigen (MNDA) is a nuclear antigen known to be expressed in mature myelomonocytic cell lines. An extensive immunocytochemical evaluation of fixed tissues confirmed MNDA expression in normal maturing granulocytes and monocytes and in acute nonlymphocytic leukemias and chronic myelogenous leukemia. MNDA was not detected in normal tissue histiocytes but was found in activated macrophages and foreign body giant cells associated with inflammation. Flow cytometric cell sorting of normal bone marrow established that MNDA is initially expressed in myeloid blast cells. Examination of lymphoid tissues showed a low level of expression in a population of normal mande B lymphocytes but not in germinal center cells or plasma cells. A subset of B cell neoplasms expressing MNDA included hairy cell leukemia, parafollicular (monocytoid) B cell lymphoma, mantle cell lymphoma, and small lymphocytic lymphoma. Cell sorting of normal bone marrow showed MNDA expression in CD20+/CD10-/CD5- B cells. MNDA was not detected in other normal bone marrow or all other nonhematopoietic cells. The hematopoietic cell-specific pattern of MNDA expression was elucidated through a comprehensive analysis of normal and neoplastic tissues, and the results provide further evidence of the coexpression of B- and myeloid cell markers in neoplastic B cells and identify a normal B cell population that might be related to the cell of origin of a subset of B cell neoplasms.
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PMID:Immunocytochemical analysis of MNDA in tissue sections and sorted normal bone marrow cells documents expression only in maturing normal and neoplastic myelomonocytic cells and a subset of normal and neoplastic B lymphocytes. 1049 38

The INK4A/ARF locus yields two tumor suppressors, p16INK4A and p14ARF, and is frequently deleted in human tumors. We studied their mRNA expressions in 41 hematopoietic cell lines and in 137 patients with hematological malignancies; we used a quantitative reverse transcription-PCR assay. Normal peripheral bloods, bone marrow and lymph nodes expressed little or undetectable p16INK4A and p14ARF mRNAs, which were readily detected in 12 and 17 of 41 cell lines, respectively. Patients with hematological malignancies frequently lacked p16INK4A expression (60/137) and lost p14ARF expression less frequently (19/137, 13.9%). Almost all patients without p14ARF expression lacked p16INK4A expression, which may correspond to deletions of the INK4A/ARF locus. Undetectable p16INK4A expression with p14ARF expression in 41 patients may correspond to p16INK4A promoter methylation or to normal expression status of the p16INK4A gene. All patients with follicular lymphoma (FL), myeloma or acute myeloid leukemia (AML) expressed p14ARF while nine of 23 patients with diffuse large B cell lymphoma (DLBCL) lost p14ARF expression. Patients with ALL, AML or blast crisis of chronic myelogenous leukemia expressed abundant p16INK4A mRNAs more frequently than patients with other diseases (12/33 vs 6/104, P < 0.01). Patients with FL and high p14ARF expression had a significantly shorter survival time while survival for patients with DLBCL and increased p14ARF expression tended to be longer. These observations indicate that p16INK4A and p14ARF expression is differentially affected among hemato- logical malignancies and that not only inactivation but also increased expression may have clinical significance.
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PMID:Expression of p16INK4A and p14ARF in hematological malignancies. 1055 50

We have studied 215 male patients (aged 45-97 years) whose sole cytogenetic abnormality was clonal loss of the Y chromosome in metaphase cells from unstimulated cultures. The patients comprised a control group with no evidence of hematologic disease and four disease case groups: 1) myelodysplastic syndrome (MDS), refractory anemia, refractory anemia with excess blasts (RAEB), RAEB in transformation, and chronic myelomonocytic leukemia; 2) acute myelogenous leukemia; 3) myeloproliferative disorder (MPD), chronic granulocytic leukemia, and polycythemia vera; and 4) B-cell lymphoma/leukemia. The frequency of cells with Y loss increased with age and was significantly greater in cases than in controls, but it was not correlated with survival or with prior therapy. The frequency of cases with a -Y clone was 6.3% of male karyotypes and represented 16.4% of all abnormal male cytogenetic reports. Much of the difference between cases and controls appears to be accounted for by a greater frequency of cases with > 75% Y loss. A value of 81% chromosome Y loss maximized the combined sensitivity (28%) and specificity (100%) for predicting disease status, but a 75% cutoff provided the best estimate of disease risk. Even in older males, if > 75% of metaphase cells are 45,X,-Y, they probably represent a disease-associated clonal population, and it is possible that the critical genetic change is not visible through the microscope. This observation is true for MDS, MPD, B-cell disease, and especially acute myelogenous leukemia. The prognostic association of Y chromosome loss for survival appears to be neutral or favorable. Genes Chromosomes Cancer 27:11-16, 2000.
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PMID:Clinical significance of Y chromosome loss in hematologic disease. 1056 81

By searching the expressed sequence tag database, a novel murine tumor necrosis factor receptor designated TNFRSF19 was identified. TNFRSF19 cDNA encodes a putative membrane protein of 348 amino acids with one incomplete and two complete cysteine-rich motifs within its extracellular region and a large cytoplasmic domain. TNFRSF19 mRNA can be detected in most murine tissues examined, particularly in brain, reproductive organs, and late developmental stages of murine embryo, but not in tissues of the immune system. The cell surface expression of the ligand of TNFRSF19 is highly restricted. Of 22 human and murine cell lines examined by FACS analysis, only Raji (B cell lymphoma cell line), GM847 (fibroblast cell line), 293 (embryonic kidney cell line), and K562 (chronic myeloid leukemia) were positive. TNFRSF19 did not bind newly cloned TNF ligands, including TWEAK (HGMW-approved symbol TNFSF12), VEGI/TL1 (HGMW-approved symbol TNFSF15), TL6/endokine (HGMW-approved symbol TNFSF18), APRIL (HGMW-approved symbol TNFSF13), OPGL (HGMW-approved symbol TNFSF11), LIGHT (HGMW-approved symbol TNFSF14), or BAFF/THANK (HGMW-approved symbol TNFSF13B) by enzyme-linked immunosorbent assay and FACS analyses. Overexpression of TNFRSF19 transduced neither apoptotic signaling nor signals leading to NF-kappaB induction. Taken together with the data that the TNFRSF19 extracellular domain-immunoglobulin fusion protein did not affect the allogeneic mixed lymphocyte reaction, our data indicate that TNFRSF19 is not involved in the modulation of immune responses.
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PMID:Characterization of TNFRSF19, a novel member of the tumor necrosis factor receptor superfamily. 1058 76

This report describes two cases of Philadelphia chromosome-negative (Ph(-)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph(+)) chronic myelogenous leukemia (CML). Lymph node biopsy of patient 1 was initially diagnosed as diffuse large B cell non-Hodgkin's lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admixed lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admixed neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively. DNA obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL. Therefore, these cases were not diagnosed as an extramedullary localized blast crisis in CML, but as Ph(-) NHLs. This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking BCR/ABL, in patients with Ph(+) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of CML. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that 'Ph(+) NHL' occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph(+) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm. Leukemia(2000) 14, 169-182.
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PMID:Ph-negative non-Hodgkin's lymphoma occurring in chronic phase of Ph-positive chronic myelogenous leukemia is defined as a genetically different neoplasm from extramedullary localized blast crisis: report of two cases and review of the literature. 1063 93

The Bcl10 gene was identified through characterization of the t(1;14)(p22;q32) associated with mucosa-associated lymphoid tissue (MALT) lymphoma. Bcl10 is implicated in the regulation of apoptosis and has been reported to be mutated in other subtypes of non-Hodgkin's B-cell lymphoma (B-NHL) and leukaemic cell lines, raising the possibility that its deregulation could be implicated in other forms of haematological malignancy. We screened 226 cases, including 123 acute myeloid leukaemia (AML), 50 acute lymphoblastic leukaemia (ALL), 20 chronic myeloid leukaemia (CML), 10 chronic lymphocytic leukaemia-prolymphocytic leukaemia (CLL/PLL) and 23 cases with 1p abnormalities, for Bcl10 mutations by reverse transcription polymerase chain reaction-single-stranded conformation polymorphism (RT-PCR/SSCP). Three known polymorphisms and two common splice variants were identified; however, no mutations were detected. One splice variant led to a 33-bp in frame deletion, whereas the other caused a 16-bp deletion predicting C-terminal truncation of Bcl10. However, both splice variants were also detected in normal bone marrow, suggesting that they are unlikely to be of pathogenetic significance. Furthermore, Southern blot analysis revealed no rearrangements of Bcl10 among 16 ALL and 11 cases of haematological malignancy with 1p abnormalities. Our results suggest that mutation of the Bcl10 gene as a mechanism of tumorigenesis is not associated with leukaemia.
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PMID:Screening for mutations of Bcl10 in leukaemia. 1088 11

Survivin is a newly discovered inhibitor of the apoptosis protein, IAP, expressed during development and in human cancers. The effector cell protease receptor-1 (EPR-1) gene is oriented in the opposite direction on the same DNA double strand. Thus, the Survivin and EPR-1 (Survivin/EPR-1) genes exist in a head-to-head configuration. It is not clear whether mutual expression of the Survivin/EPR-1 genes occurs in both normal cells and cancer cells. Here, we investigated the mutual expression of the Survivin/EPR-1 genes in 12 normal peripheral blood (PB) specimens, seven normal bone marrow (BM) specimens, five lymph node (LN) specimens, and seven leukemic cell lines, and 27 patients with malignant lymphoma (ML), four with acute lymphocytic leukemia (ALL), three with acute myelocytic leukemia (AML), and four with chronic myelocytic leukemia in blastic crisis (CML-BC). Using Northern blot analysis, small amounts of EPR-1 mRNA were detected in normal PB, normal BM and LN specimens, but no Survivin mRNA was detected. However, Survivin mRNA was detected in two of the 12 normal PB, six of the seven normal BM and one of the five LN specimens using reverse transcription and polymerase chain reaction (RT-PCR). Expression of both the Survivin and EPR-1 genes was detected in six of the seven cell line samples by Northern blot, and in all of them by RT-PCR. Mutual expression of the Survivin and EPR-1 genes was detected in three of the four CML-BC samples, 15 of the 27 ML samples, two of the four ALL samples, and all three AML samples using the RT-PCR method. No EPR-1 expression with or without Survivin expression was clearly detected in eight of the nine diffuse large B-cell lymphoma (DLB) specimens, two of the six follicular center lymphoma specimens, one of the four specimens of nodular sclerosis of Hodgkin's lymphoma, two of the four ALL specimens or one of the four CML-BC specimens. The data presented here show that disrupted expression of the Survivin/EPR-1 genes occurred in many kinds of hematologically malignant cells. This may be of biological importance.
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PMID:Disturbed expression of the anti-apoptosis gene, survivin, and EPR-1 in hematological malignancies. 1108 80

We describe the rare coexistence at the time of diagnosis of Philadelphia positive chronic myelogenous leukemia (Ph+ CML) and non-Hodgkin's lymphoma (NHL). At the time of diagnosis, cytogenetic analysis of peripheral blood and bone marrow cells revealed the Ph chromosome translocation in all examined metaphases. The lymph node biopsy showed features of diffuse large B-cell lymphoma (DLBCL). This case may be of interest due to: (1) the rare coexistence of Ph+ CML and NHL at diagnosis, (2) the fact, that in contrary with previously reported cases in patients with antecedent or concurrent diagnosis of CML, where precursor lymphoblastic lymphomas are prevalent, in our patient clinical and laboratory findings revealed a diffuse large B-cell lymphoma, and (3) that the present case is an additional one confirming the poor outcome of patients with simultaneous occurrence of these two clinical entities.
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PMID:Coexistence of Philadelphia-positive chronic granulocytic leukemia and diffuse large B-cell lymphoma at initial diagnosis. 1199 82

A nondifferentiating mouse myeloid leukemia cell line produces differentiation-inhibiting factors. One of these factors was purified as a homologue of nm23. The nm23 gene was isolated as a metastasis-suppressor gene that exhibits low expression in high-level metastatic cancer cells. The nm23 gene was overexpressed in acute myelogenous leukemia (AML) cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. The overexpression of nm23-H1 was also observed in various hematological neoplasms. To use nm23 overexpression to determine the prognosis for lymphoma, we established an enzyme-linked immunosorbent assay (ELISA) technique to determine the serum level of nm23-H1 protein. This assay is far simpler than that used to determine nm23 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Using this system, we measured nm23-H1 protein levels in many hematological malignancies. Serum nm23-HI levels were significantly higher in patients with all of the hematological neoplasms tested (AML, chronic myelogenous leukemia, acute lymphoblastic leukemia, (ALL) myelodysplastic syndrome (MDS) and malignant lymphomas) than in normal controls. An elevated serum nm23-H1 protein concentration predicted a poor outcome for AML and non-Hodgkin's lymphoma. Especially in diffuse large B-cell lymphoma (DLBCL), seram nm23-H1 protein levels were an important prognostic factor in planning an appropriate treatment strategy for DLBCL. The serum nm23-H I protein levels probably depend on the total mass of malignant cells overexpressing nm23-H1.
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PMID:Serum nm23-H1 protein as a prognostic factor in hematological malignancies. 1215 76

The Fifteenth International Symposium of the Foundation for Promotion of Cancer Research entitled 'New Horizons in the Diagnosis and Treatment of Hematological Malignancies Based on Molecular Genetic Features' was held in Tokyo on January 15-17, 2002. Twenty-nine invited speakers, including 12 from abroad and 17 from Japan, presented the updated results of their research. After an overview of the classification of hematological malignancies, new findings on some disease entities based on novel immunophenotypic and molecular genetic features were presented. The results of gene expression profiling and BCL6 and C-MYC gene rearrangement in diffuse large B-cell lymphoma were presented and oncogenic mechanism of acute myeloid leukemia was discussed. In the treatment of non-Hodgkin's lymphoma and acute leukemia, the present consensus and future directions were discussed based on the results of multicenter trials in the USA and Japan. As a molecular targeting therapy, the remarkable effect of a BCR-ABL tyrosine kinase inhibitor, STI571, in chronic myeloid leukemia and gastrointestinal stromal tumor was presented. Thereafter, promising results of active immunotherapy, chimeric anti-CD20 monoclonal antibody, anti-CD20 radioimmunoconjugate and anti-CD22 immunotoxin for B-cell lymphoma were presented. Finally, recent advances in allogeneic hematopoietic stem cell transplantation were discussed, focusing on reduced-intensity preparative regimens. The recent advances in basic and clinical research on hematological malignancies would lead to further improvement in the prognosis and quality of life of patients suffering from leukemia or lymphoma.
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PMID:Report of the fifteenth international symposium of the foundation for promotion of cancer research: new horizons in the diagnosis and treatment of hematological malignancies based on molecular genetic features. 1241 6


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