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)

We have studied point mutations in exons 5-8 of the p53 gene in the myelodysplastic syndromes (MDS) by using polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) analysis and direct nucleotide sequencing. The subtypes examined were: refractory anaemia (RA), refractory anaemia with ring sideroblasts (RARS), chronic myelomonocytic leukaemia (CMML), refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEBt), and acute myeloid leukaemia (AML) which had evolved from MDS. 26 cases of MDS were studied. 12 of these were sequentially sampled but none changed its p53 status during the time of the study (18 months). Four mutations (one nonsense and three missense) were identified. Each case with a mutation was of an advanced MDS subtype, suggesting that p53 mutation in these diseases is a terminal genetic event in the process of leukaemogenesis. The nonsense mutation inserted a premature stop codon in a case of AML which had evolved from RAEB; this mutation has been reported before in both chronic myeloid leukaemia (CML) and Burkitt's lymphoma. The three missense mutations have not previously been reported in haematological malignancies.
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PMID:p53 mutation in the myelodysplastic syndromes. 783 78

The expression of the human myeloid cell nuclear differentiation antigen (MNDA) was observed specifically in cells of the granulocyte-macrophage lineage in our earlier reports. The specificity of MNDA expression for cells in the granulocyte-macrophage lineage was reexamined in cell lines established from patients with Philadelphia chromosome-positive chronic myeloid leukemia. Cell lines that expressed MNDA exhibited myeloid cell features and granulocyte or monocyte differentiation could be induced in vitro, while cell lines exhibiting properties of very early stage cells or multipotential cells did not express MNDA. Cells originating from cases of Burkitt's lymphoma were negative. By contrast, three lymphoblastoid cell lines (immortalized in vitro with Epstein-Barr virus) were weakly positive and MNDA was up-regulated by interferon-alpha (IFN-alpha) treatment. As we reported previously, MNDA mRNA level in adherent monocytes is elevated by IFN-alpha; in this study, we further assessed MNDA expression in in vitro monocyte-derived macrophages. Three additional agents (endotoxin, phytohemagglutinin, and phorbol ester) and other conditions that affect function, cytokine production, differentiation, and/or growth of monocytes were examined for their ability to alter MNDA expression. The results varied with the agent, cell type, and stage of differentiation. Changes in MNDA expression occurred slowly (hours to days), suggesting that MNDA could mediate changes realized over a long period. The results also reveal a discordance in certain MNDA positive cells between steady-state levels or changes in levels of protein and mRNA indicating that the regulation of MNDA expression occurs at more than one point. Changes in MNDA expression are consistent with a role in opposing macrophage differentiation and activation of monocytes/macrophages.
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PMID:Regulation and specificity of MNDA expression in monocytes, macrophages, and leukemia/B lymphoma cell lines. 789 Aug 14

Many haematologic malignancies carry characteristic chromosomal translocations, which are thought to play an important role in the pathogenesis of these tumours. The t(8; 14) translocation in Burkitt's lymphoma was one of the first characterized at the molecular level. In this translocation the c-myc oncogene at chromosome 8q24 becomes deregulated by enhancer elements of the immunoglobulin heavy chain locus at chromosome 14q32 leading to a very aggressive B cell malignancy. Translocations involving an overexpressed c-myc gene are also found in AIDS-associated lymphoma or in T cell leukaemias, or they develop during tumour progression of a low grade B cell malignancy into a high grade B cell tumour in an additional cytogenetic change. A different mechanism of oncogene activation in a leukaemia specific chromosomal abnormality is found for CML, where c-abl sequences are fused into the bcr locus, or in the t(4; 11) of acute childhood leukaemia involving the recently identified ALL-1 gene at chromosome 11q23 resulting in a malfunctioning, structurally altered oncogene. Thus, in the past molecular and somatic cell genetic studies have clarified many details in aetiology and progression of leukaemias and lymphomas which are useful for applications in clinical diagnostics, and which in the future will be helpful in designing a therapy based on a molecular understanding.
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PMID:Chromosomal translocations in leukaemia. 814 18

Various kinds of nonrandom chromosomal aberrations have been reported in hematopoietic malignancies. Since the 1980s, many translocation-associated oncogenes and several suppressor oncogenes have been identified and applied for the clinical diagnosis of these malignancies. The former is of major, clinical importance for specific diagnosis made on the basis of molecular detection of the chromosomal translocation, the deregulated expression, and the chimeric mRNA of those genes. Both BCL-1 and BCL-2 genes, associated with mantle zone lymphoma and follicular lymphoma, respectively, belong to the representative deregulated oncogenes by juxtaposition with an immunoglobulin gene enhancer as well as an MYC gene in Burkitt's lymphoma. On the other hand, the MLL gene, associated with infant leukemia, acute monocytic leukemia and secondary leukemia, produces chimeric mRNAs between LTG4, 9, and 19 genes as well as the BCR-ABL chimeric gene in chronic myelogenous leukemia. The detection of minimal residual disease (MRD) by either polymerase chain reaction (PCR) or reverse transcriptase (RT)-PCR is becoming an essential test during the course of treatment containing bone marrow transplantation, because positive results of the MRD are closely related to poor prognosis and would have great influence on the choice of treatment plans.
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PMID:[Molecular diagnosis of leukemia and lymphoma]. 817 45

Mutations of the P53 tumor suppressor gene represent the most common genetic lesion in human solid tumors. In hematological malignancies, P53 alterations are detected in the evolution of the chronic myelogenous leukemia to myeloid blast crisis. P53 mutations were also found to be associated with Burkitt's lymphoma and HTLV-1 related adult T-cell leukemia. These results support the notion that alterations of the P53 gene may be involved in the progression of these hematological diseases.
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PMID:[P53 genes and malignant hematologic diseases]. 820 51

Using 7-amino-actinomycin-D/pyronin Y (7AAD/PY), we analyzed the surface phenotypes and cell cycle of 22 hematopoietic cell lines based on their cellular DNA/RNA content. Populations of G1a, G1b, S, and G2M, the DNA index (DI), and the RNA index of S phase (SRI) were calculated by means of DNA/RNA dot plots. Two new parameters were extracted from the cell-cycle profiles: the nucleic acid index of S phase (NI) and the coefficient of variations in the RNA at S phase (SVC). DNA/RNA dot plots of cell lines revealed four characteristic profiles of the cell cycle, defined with the calculated NI and SCV. These were type 0 (small NI, large SCV), type I (small NI, small SCV), type II (large NI, small SCV), and type III (large NI, large SCV). Type O included four stem cell lines: one t(1;19) leukemia, two Ph1+ acute lymphocytic leukemia (ALL), and one biphenotypic crisis of chronic granulocytic leukemia (CGL). Type I included five ALL cell lines: three T-ALL and two common B-ALL. Type II contained 10 myeloid cell lines: five AML and five myeloid crisis of CGL. Type III contained three relatively immature lymphoma cell lines: two Burkitt's lymphoma and one follicular center lymphoma. Calculated NI/SCV (%) were as follows: type 0, 2.27 +/- 0.19/16.7 +/- 3.7; type I, 2.20 +/- 0.30/11.1 +/- 0.7; type II, 3.64 +/- 0.52/11.8 +/- 1.0; and type III, 3.60 +/- 0.53/17.5 +/- 1.9. Cell-cycle analysis of blasts using 7AAD/PY combined with surface phenotyping may yield important information for classifying hematopoietic malignancy within 2 hours of patient admission.
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PMID:Profile of cell cycle in hematopoietic malignancy by DNA/RNA quantitation using 7AAD/PY. 869 48

Recent advances in molecular biological techniques have contributed to the tremendous progression made in the field of diagnosis of leukemia. Discovery of T- or B-lymphocyte associated genes, tumor specific genes and genes involved in chromosomal translocation has made it possible to detect leukemia cells by Southern blotting, PCR, RT-PCR or fluorescence in situ hybridization (FISH). The recently developed FISH is a simple, rapid and accurate method and requires a very small amount of specimen (about 500-1000 cells). It is possible to obtain results within 48 hours of sampling. This lecture were focused on two topics; 1) The application of FISH method in the diagnosis of leukemia using three types of probes (whole chromosome painting probe, centromeric probes and oncogene specific probes) and their combinations. 2) Clarification of concepts made by molecular biology especially in Philadelphia chromosome positive leukemia, Ph-negative chronic myelocytic leukemia, endemic/sporadic type of Burkitt's lymphoma, biphenotypic leukemia and leukemia with specific translocations.
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PMID:[Progress in diagnosis of leukemia]. 881 59

In this study, we examined a large number of patients to clarify the distribution and frequency of a recently described FLT3 tandem duplication among hematopoietic malignancies, including 112 acute myelocytic leukemia (AML), 55 acute lymphoblastic leukemia (ALL), 37 myelodysplastic syndrome (MDS), 20 chronic myelogenous leukemia (CML), 30 non-Hodgkin's lymphoma (NHL), 14 adult T cell leukemia, 15 chronic lymphocytic leukemia (CLL) and 38 multiple myeloma (MM). We also evaluated 71 cell lines derived from 11 AML, 31 ALL, two hairy cell leukemia, three acute unclassified leukemia, 10 CML, 12 NHL including six Burkitt's lymphoma, and two MM. Using genomic PCR of exon 11 coding for the juxtamembrane (JM) domain and first amino acids of the 5'-tyrosine kinase (TK) domain, this length mutation was found only in AML (22/112, 20%) and MDS (1/37). According to the FAB subclassification, they were 5/18 (28%) of M1, 4/29 (14%) of M2, 3/17 (18%) of M3, 6/24 (25%) of M4, 4/20 (20%) of M5 and 1/9 of refractory anemia with excess of blast in transformation. In the various cell lines examined, this abnormality was determined in only one derived from AML and never found in other hematological malignancies. The sequence analysis of the abnormal PCR products revealed that 23 of 24 showed internal tandem duplication with or without insertion of nucleotides. In one AML, insertion and deletion without duplication was determined. All 24 lengthened sequences were in-frame. Duplication takes place in the sequence coding for the JM domain and leaves the TK domain intact. In conclusion, we emphasize that the length mutation of FLT3 at JM/TK-I domains were restricted to AML and MDS. Since all these mutations resulted in in-frame, this abnormality might function for the proliferation of leukemic cells.
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PMID:Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines. 932 77

Several new 4-diazopyrazole derivatives were synthesized by reaction of 1-(R-substituted)phenyl-3-methyl-5-benzamidopyrazoles with a sevenfold excess of nitrous acid in acetic media. The compounds were tested at 20 microM concentration for their antineoplastic activity in vitro against Raji (human Burkitt lymphoma), K562 (human chronic myelogenous leukemia) and U937 (human histiocytic lymphoma) cell lines. They showed a percent of growth inhibition in the range 23.4-100%.
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PMID:Synthesis and antineoplastic activity of new 4-diazopyrazole derivatives. 950 64

We investigated the expression-percentage as well as MESF values ("molecules of equivalent soluble fluorochrom" that represent approximately the density of marker expression) of HLA-DR, CD71 and CD38 markers in some human leukemias (ALL, AML, CLL, CML) and lymphomas. They are non-lineage restricted and are supposed to be activation markers except for cases where they represent pathological phenotype like HLA-DR in pre B-ALL, CD38 in some M0 AML or in plasmocytoma or CD38 and CD71 in less mature T-ALL. We used flow cytometry, immunofluorescent staining, DNA staining by propidium iodide and quantification by calibration particles. We demonstrated increased MESF values of HLA-DR compared with controls in all investigated disorders, what could have a prognostic value. We demonstrated significantly higher MESF values of HLA-DR in cALL (37,300-46,000) in comparison with AML (9400-12,400), what could represent another important parameter when distinguishing between these two groups of leukemia. In cells of CML patients with lower CD38% and CD71% increased MESF values (5100 for CD38 and 7900 for CD71), were found while in some T-ALL, AML and cALL patients with high percentages of CD71 and CD38 there were lower MESF values what could indicate a possible connection of higher stage of cell maturation with increased density of CD38 and CD71 markers. We investigated possible relationship between percentage of expression of HLA-DR, CD38 and CD71 and proliferation rate by DNA analysis of the cell cycle. In a group of non-Hodgkin's lymphoma patients, there was no significant increase of proliferation index of malignant cells compared with control. The correlation between percentage of expression of mentioned parameters and proliferation index was not significant. In one patient with Burkitt's lymphoma we demonstrated significant increase of proliferation index of CD71+ subpopulation compared with CD71- one, what indicates that in aggressive form of NHL CD71 can be evaluated not only as activation but also as proliferation marker.
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PMID:The relationship of HLA-DR, CD38 and CD71 markers to activation, proliferation and differentiation of some human leukemia and lymphoma cells. 968 89


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