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

A cell line with immature blast cell morphology was isolated from HL-60 promyelocytic leukemia cell cultures and designated HL-T. This new cell type is biphenotypic, expressing terminal transferase (TdT) together with myelomonocytoid immunologic features. TdT enzymatic activity, undetectable in HL-60, was determined to be 140 to 180 units/10(8) HL-T cells by the dGTP-assay, approximately 20% of the activity found in lymphoblastoid cell lines. HL-T predominantly synthesize the known 58-kDa TdT-protein plus a minor 54/56-kDa doublet. The 58-kDa steady state form is nonglycosylated and is phosphorylated. Precursor antigens S3.13 and MY-10, absent on HL-60, are expressed by HL-T; however, the cells are negative for HLA-Dr. Southern blot analysis by hybridization with immunoglobulin heavy chain (JH) and T cell-receptor chain gene (T beta) probes shows JH to be in the germ-line configuration in both cell lines and the T beta gene to be in germ-line in HL-60 but to be rearranged in HL-T. Truncation of the gene encoding the granulocyte-macrophage-colony-stimulating factor (GM-CSF), as found in HL-60, is not observed in HL-T. HL-T are resistant to differentiation-induction by retinoic acid and 1,25-dihydroxyvitamin D3. Cytogenetically HL-T share with HL-60 a deletion of the short arm of chromosome 9 at breakpoint p13, an aberration frequently found in patients with T cell leukemia. In addition, HL-T display t(8;9)(p11;p24) and trisomy 20. Tetraploidy is observed in 80% of HL-T metaphases with aberrations identical to those in the diploid karyotype. Like HL-60, the new line shows some surface-antigenic-T cell characteristics. Despite an antigenic pattern most consistent with that of helper-inducer T cells (T4+, D44+/-, 4B4+, 2H4-, TQ1+/-), HL-T cells and their conditioned culture medium suppress antigen, mitogen, and mixed-leukocyte-culture-mediated lymphocyte proliferation.
 ...
PMID:HL-T, a new cell line derived from HL-60 promyelocytic leukemia cell cultures expressing terminal transferase and secreting suppressor activity. 330 49

This paper analyzes the hematologic features and outcome of 13 patients with chromosome 5 abnormalities (monosomy 5 or deletion of 5q), either isolated or with additional anomalies. Among four patients with isolated del (5q), two had a stable refractory macrocytic anemia with thrombocytosis (5q-syndrome). All nine patients with complex karyotypes had acute leukemia or refractory anemia with excess of blasts in acute transformation; two cases were TdT-positive, with a lymphoid or a mixed phenotype. In seven patients, preleukemia preceded overt leukemia, and in six, a prior therapeutic, or occupational exposure to mutagens/carcinogens had occurred. Additional chromosome 7 abnormalities were seen in four cases. The median survival of patients with complex karyotypes was 19 months from the time of diagnosis of the hematologic disorder and 5 months from the time of identification of the chromosome 5 abnormality. Pathogenetic implications of the chromosome 5 monosomy or del (5q) through a proto-oncogene activation and the putative hemopoietic stem cell involvement in a clonal disease are discussed.
 ...
PMID:Hematologic and clinical features of patients with chromosome 5 monosomy or deletion (5q). 335 40

Serial samples of peripheral blood were obtained from 75 children with acute lymphoblastic leukemia in remission. An immunofluorescence assay was used to quantitate TdT-containing (terminal deoxynucleotidyl transferase-containing) cells in the mononuclear leukocyte fraction of these specimens. Nine relapses in 8 patients were preceded by elevations (0.12-0.70%) in peripheral blood terminal deoxynucleotidyl transferase-containing cells noted 1-33 weeks prior to relapse. No such elevations were observed prior to 6 relapses in 4 patients. Peripheral blood terminal transferase deoxynucleotidyl-containing cells were elevated (0.12-0.61%) in 22 children who did not relapse over a 5-82 week period of observation. The sensitivity (67%) and specificity (68%) of this assay are inadequate to establish which patients have minimal residual leukemia.
 ...
PMID:Terminal deoxynucleotidyl transferase (TdT)-containing peripheral blood mononuclear cells during remission of acute lymphoblastic leukemia: low sensitivity and specificity prevent accurate prediction of relapse. 347 80

1255 cases of leukemia-lymphoma were tested between 1972 and 1984 by multiple marker analysis. Routine leukemia phenotyping was performed using standard morphological and cytochemical techniques in combination with clinical and histo-pathological information; the main emphasis was put on immunological surface marker analysis using erythrocyte rosette assays, TdT and a large panel of poly- and monoclonal antibody tests. The 1255 cases were divided into these major types and subtypes: 349 cases of ALL and related immature T- and Burkitt-lymphomas (cALL, pre B-ALL, B-ALL and Burkitt-lymphomas, T-ALL and immature, mostly leukemic T-lymphomas, Null-ALL), 454 cases of mature T- and B-cell malignancies (T-CLL, mycosis fungoides, Sezary-syndrome, T-lymphomas, B-CLL, hairy cell leukemia, multiple myeloma, B-lymphomas), 263 cases of acute myeloid leukemias (AML, AMMoL/AMoL), 182 cases of chronic myeloid leukemias (CML in chronic phase, CMoL, CML in blast crisis), 6 cases of erythroleukemia and 1 case of megakaryoblastic leukemia. A simplified classification scheme which has been used in our laboratories is presented. Phenotyping is of diagnostic, prognostic and therapeutic relevance, most evidently for patients with ALL. Routine leukemia phenotyping should be performed with highly standardized techniques and reagents and by combining information from several fields in the multiple marker analysis. New areas of leukemia research might become very useful for the routine procedure of phenotyping.
 ...
PMID:Phenotyping of malignant hematopoietic cells. Analysis of 1200 cases of leukemia-lymphoma. 348 82

A case of infantile acute leukemia associated with translocation t(4:11)(q21:q23) is reported. This leukemia has a very poor prognosis, and this patient survived for only 9 months. The blast cell morphology was L1/L2 according to the FAB classification and showed a lymphoid appearance on transmission electron microscopy. The histochemical stains showed a pattern of periodic acid-Schiff positivity and variable alpha-naphtyl acetate staining. The cells were TdT-positive and surface-marker phenotyping was positive for Ia-like and B4 antigens but negative for CALLA, T-cell markers, myelocyte and monocyte markers. The leukemic cells represent a frozen state of a very early precursor, corresponding to the earliest recognizable stage of the B-cell lineage. This observation may contribute to the controversion regarding the cell origin of this unique leukemia associated with t(4:11), lymphatic versus null cell, early myeloid, or mixed, and points to the possibility of a very early B-cell lineage leukemia.
 ...
PMID:Leukemia of early infancy. Early B-cell lineage associated with t(4:11). 348 3

A 17-year old caucasian male presented with B-cell acute leukemia which proved aggressive and refractory to treatment. Cytogenic investigation showed a single clone with a complex karyotype 49,XY,del(2)(p13),+4,del(4)(p11),-6,+i(6)(p),+7,+8, t(8;14), (q24;q32),del(17)(p11). This includes the Burkitt's translocation and a deletion at the site of the immunoglobulin kappa light chain gene. Clonal evolution included tetraploidy, duplication of the derived chromosomes and, terminally, trisomy 1q. Immunological investigation revealed a monoclonal population of B-cell blasts, expressing the kappa light chain, and with an extremely rare combination of SIg and TdT positivity. Immunoglobulin gene rearrangement confirmed monoclonalility. Tetraploidy of the clone and del(17)(p11) have been previously described only in a cell line or at end stage disease in B-ALL. It is suggested that the chromosomal abnormalities present at diagnosis were directly related to the refractory nature of this leukemia.
 ...
PMID:Multiple chromosome abnormalities in a drug resistant TdT positive B-cell leukemia. 349 93

Clinical and laboratory features of seven patients with acute leukemia associated with the (4;11) chromosome translocation are presented. Leukemic blasts of these patients showed lymphoid morphology in 6 (although 1 was treated for monoblastic leukemia 3 years earlier) and monocytoid morphology in 1, were positive for TdT and HD 37 (CD 19) in 6 patients, whereas weak expression of CALLA was seen in only 1 patient and T-lineage-associated antigens in none. Leukemic blasts from four patients showed the simultaneous expression of B-lymphoid and myeloid antigens, suggesting leukemogenesis in a very early multipotent progenitor cell. In 2 patients an isochromosome of the long arm of No. 7 chromosome was found in the leukemic karyotypes in addition to t (4; 11) (q 21; q 23); in one instance present at diagnosis, in the other one occurring at relapse. In one other patient leukemia karyotype also demonstrated trisomy 8. Leukemic cells of three patients were investigated by molecular genetics and demonstrated immunoglobulin gene rearrangements for the Ig heavy chain sequences but not for the light chain constant regions and T cell receptor sequences. All patients were treated by intensive chemotherapy. Four of the 7 patients are in continuous complete remission. The longest event-free survival time (over 2 1/2 years) was seen in one patient who had also DOWN-syndrome. Including these 7 patients a clinical analysis of 71 patients with t (4; 11) acute leukemia was made, emphasizing the following characteristics at diagnosis: female sex (62%), age under 2 years (49%), leukocyte count over 100 X 10(9)/1 (61%), splenomegaly (80%), CNS-disease (11%). Survival of over 2 years was reported in less than 15% of the patients. It remains to be seen if risk-adapted treatment can alter the course of this early B-precursor acute leukemia with hitherto very bad prognosis.
 ...
PMID:Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases. 349 35

Until recently, lineage fidelity was thought to be preserved in leukaemic cells, which by available tests showed surface markers and enzymatic patterns characteristic of an appropriate normal cell lineage and stage of differentiation. Our data indicate that this theory is too restrictive. If leukaemogenesis occurs in pluripotent progenitors in a relatively high percentage of cases, we would propose a model in which lymphoid and myeloid differentiation antigens are expressed simultaneously until the progenitor cell commits to a single lineage. Lineage commitment could involve external factors, e.g. growth factors (Sherr et al, 1985), that cause genes specific for the opposite lineage to be 'switched off'. The control of gene expression in mammalian cells and the specific chromosomal sites of genes coding for the various lineage-associated markers remain uncertain. However, recent studies indicate that most, if not all, leukaemic cells contain chromosomal abnormalities, many involving rearrangements of DNA (Williams et al, 1986). Since the control of eukaryotic gene expression is known to involve numerous sequence elements, some acting at a distance from the site of transcription (Dynan and Tjian, 1985), genetic perturbations within the cell (e.g. a reciprocal translocation) could be expected to deregulate certain genes, leading to their under- or overexpression analogous to activation of the c-myc oncogene by the 8;14 translocation in Burkitt's lymphoma. Thus, an almost infinite variety of cell lineage-related phenotypes could be expected from this mechanism alone, even if the transforming event did not involve a pluripotent stem cell. Also, we have hypothesized that enzymes such as TdT, a DNA polymerase that catalyses polymerization of deoxyribonucleotides without a DNA template, could serve as a modifier of DNA sequences, permitting otherwise inactive genes to be expressed (Stass and Mirro, 1985). It is interesting that most cases of childhood acute mixed-lineage leukaemia are TdT positive, even though this is not true for the chronic leukaemias of adults. It is now clear that unusual combinations of myeloid and lymphoid cell lineages are much more common in acute leukaemia than have been generally recognized or suspected. The traditional division of the acute leukaemias into ALL and AML may not be the most accurate way to represent this class of haematological malignancies. That mixed-lineage leukaemia may require alternative therapy is a clinically important observation and underscores the need for comprehensive testing of blast cells at diagnosis.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Lineage heterogeneity in acute leukaemia: acute mixed-lineage leukaemia and lineage switch. 353 42

This study shows the progression of a myelodysplastic syndrome (MDS) to pre-B acute lymphoblastic leukaemia (ALL) with an unusual phenotype. On diagnosis of leukaemia bone-marrow mononuclear cells were labelled with murine monoclonal antibodies HLA-DR, VIL-A1 (CALLA), 3813, VIM-D5 and with a rabbit antiserum to TdT using a double colour indirect immunofluorescence technique. In addition simultaneous detection of cytoplasmic mu chains (Cy mu) and of TdT was carried out and a direct immunofluorescence analysis for surface membrane immunoglobulins (SmIg) was performed. Two main populations were present: the major one being HLA-DR+, Cy mu+, VIM-D5+, TdT-, CALLA-, SmIg-; the minor one HLA-DR+, Cy mu+, VIM-D5-, TdT+, CALLA-, SmIg-. The progression of our case to acute leukaemia with a population of leukaemic cells each of which demonstrated features of lymphoid and myeloid cells suggests that MDS would originate at the pluripotential stem cell level.
 ...
PMID:Progression of a myelodysplastic syndrome to pre-B acute lymphoblastic leukaemia with unusual phenotype. 353 73

We evaluated a newly developed solid-phase immunoassay (EIA) of terminal deoxynucleotidyl transferase (TdT, EC 2.7.7.3) and compared it with the enzymatic assay of TdT involving DNA polymerase. We assessed the precision, performance characteristics, and clinical efficacy of the EIA procedure, using 249 specimens of peripheral blood and bone marrow and 118 specimens of whole blood. On linear regression analysis of results for these 249 samples as measured by the two procedures, the correlation coefficient was 0.87. Distribution of TdT in mononuclear cells isolated from whole blood and bone marrow of subjects in several disease categories indicated good concordance between the two assay procedures. The EIA procedure is precise, can be performed on whole blood without first isolating mononuclear cells, is nonisotopic, and shows potential as a quantitative indicator for the differential diagnosis and monitoring of human leukemia.
 ...
PMID:Solid-phase enzyme immunoassay of terminal deoxynucleotidyl transferase evaluated. 354


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>