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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the course of our efforts to characterize the EBV-carrying cells that are responsible for direct growth or the 2-step mechanism, based on virus release from the explanted cells and subsequent transformation of previously uninfected cells, we have encountered an unusual CLL patient who carried a small subpopulation of in vivo EBV-infected leukemia cells. These were predominantly present in the low-density fraction and grew into EBV-carrying lines upon explantation after a relatively short latency period, 3-4 weeks. Cytogenetic examination conclusively proved the leukemic origin of the established CLL lines. They carry a ring chromosome 15 and are trisomic for chromosome 12. The same changes are also found in the majority of the peripheral blood lymphocyte population. Taken together, our results suggest that the EBV-genome and the cytogenetic changes may have contributed to the immortalization of the CLL cells in a complementary or synergistic fashion.
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PMID:Direct outgrowth of in vivo Epstein-Barr virus (EBV)-infected chronic lymphocytic leukemia (CLL) cells into permanent lines. 283 21

The synthesis of core histone variants and of histone H1 variants was determined in fresh leukemic cells of eight patients with leukemia [seven acute lymphoblastic (ALL) and one chronic lymphocytic (CLL)], in normal lymphocytes from healthy donors or from ALL patients in complete remission. Histone variant synthesis was evaluated by incubating cells with [14C]Lys and [3H]Arg in medium without Lys and Arg and then by two-dimensional polyacrylamide gel electrophoretic separations (acetic acid-urea-Triton x-100 acetic acid-urea-hexadecyltrimethylammonium bromide for core histone variants; sodium dodecyl sulfate/acetic acid-urea-hexadecyltrimethyl ammonium bromide for H1 variants). As previously reported, quiescent lymphocytes and lymphocytes stimulated with phytohaemagglutinin (PHA) showed clearcut changes in the proportions of synthesis of core histone variants and H1 variants. Leukemic lymphocytes freshly obtained from blood showed a pattern of core histone synthesis and H1 synthesis intermediate between that of quiescent and PHA-stimulated lymphocytes; this is probably due to the presence of a mixture of resting and growing cells. When leukemic cells were stimulated to grow by mitogens, the pattern of core histone and H1 variant synthesis was similar to that in mitogen-stimulated normal lymphocytes. Histone variants whose synthesis is associated with the S-phase were not synthesized in leukemic cells treated with the DNA synthesis inhibitors hydroxyurea and 1-beta-D-arabinofuranosylcytosine (Ara-C). The pattern of acetylation of histone H4 was also apparently similar in leukemic cells and normal lymphocytes. The radioactivity associated with the ubiquitinated forms of H2A increased in nongrowing lymphocytes and in leukemic cells treated with DNA synthesis inhibitors whereas they decreased after mitogenic stimulation. Variability was wide in the synthesis of ubiquitinated H2A in different cases of leukemia. The only clear-cut difference between leukemic cells and normal lymphocytes was that leukemic cells from ALL patients, but not lymphocytes from normal donors or from ALL patients in complete remission, synthesized appreciable amounts of H1 degrees, increasing after hydroxyurea/Ara-C treatment and decreasing after PHA-stimulation. In leukemic cells from a CLL patient H1 degrees synthesis was undetectable.
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PMID:Comparison of histone variant synthesis in human lymphocytic leukemia cells and in normal lymphocytes. 283 21

Peripheral blood mononuclear cells (PBMNC) from 23 healthy subjects and 39 patients with B-cell chronic leukaemia (B-CLL) were assayed for ribonuclease H activity using as substrate the filter-immobilized synthetic homopolymer hybrid 3H-poly(rA):poly(dT). In 69% of the leukaemia patients examined enzyme activities were above those estimated in cells from the healthy controls. The mean enzyme levels for the normal and the leukaemic samples group were (per cent substrate hydrolysis): 8.1 +/- 8.9 and 58.7 +/- 40.8, respectively, their difference being statistically highly significant (P less than 0.0001). This result does not represent homogeneity within the cells but is due to a subclass of cells within the leukaemic clone containing the enzyme, thus contributing through pool size fluctuation to the wide variations of enzyme activity observed among the patients. These cells containing high activity could not be identified with either the prolymphocytes or the large lymphocytes. The activity of ribonuclease H in the examined CLL patients correlated with disease stage (Binet) (P = 0.011) and appeared to serve as a sensitive indicator of disease progression when compared with a number of other known prognostic parameters.
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PMID:Activity of ribonuclease H in cells of chronic B-lymphocytic leukaemia: correlation with clinical stage. 284 80

This thesis is a survey of nine previously published articles on MPO deficient PMN. The incidences in leukaemia and allied disorders of the presence of this abnormal subpopulation of mature neutrophils and the relationship to clinical course in AML, susceptibility to infections in AML, FAB classification in AML and MDS, cytogenetically defined aberrations in MDS and morphometrical characteristics were investigated. The aims of the studies were to examine the diagnostic as well as the prognostic value of the parameter, to examine the usefulness of the parameter as an predictive indicator of CR and relapse in AML and to examine the concept that MPO deficient PMN may originate from leukaemic precursors. MPO deficient PMN were found to occur in a minor number (less than 4% of the total number of PMN) in normal humans and the incidences of an abnormal number (greater than 4%) were found to be about 40% in AML (I, II, III, IV, VIII), 60% in CML (I, VII), 30% in MPD other than CML (VII) and 30% in MDS (V). The highest incidences in AML were found in the FAB subtypes possessing the most myeloid differentiation potential i.e. FAB M2 and FAB M4 (IV). In ALL, CLL, HCL, Hodgkin's disease, anaemia not related to leukaemia and leukaemoid reactions the incidences all were 0% (I, unpublished data). The abnormal MPO deficient PMN subpopulation, if present, disappeared when CR was achieved and reappeared when relapse eventually was developed (II, VIII). In both situations serial determinations showed that the change occurred before the usual routine blood examinations predicted CR and relapse; several days and several months prior, respectively (VIII). The probability of obtaining CR was lower in the AML patients with the abnormal subpopulation and the risk of developing relapse higher than in AML patients without the anomaly (II, VIII). These differences were not statistically significant, however. AML patients, showing an increased number of MPO deficient PMN, revealed a statistically significant increased susceptibility to infections (P less than 0.01) during the preremission phase accounting for 18% to 67% of the total number of infections in this period (III). This increase was positively correlated to the extent of the anomaly (P less than 0.002). The spontaneous occurrence of a subpopulation of MPO deficient PMN in MDS went together with a simultaneous progression in cytogenetically determined clonal chromosomal aberrations and were related to progression in FAB subtype as well (VI). Morphometrically MPO deficient PMN were characterized by a decreased total cell size and an increased nucleus size of the projected images (IX).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Myeloperoxidase deficient polymorphonuclear leucocytes in leukaemia and allied disorders. 285 15

Sixteen Italian patients with chronic T-cell lymphocytic leukaemia (T-CLL) and leukaemic T-helper phenotype lymphocytes (Thp-CLL) were investigated for serum antibodies against human T-cell leukaemia virus I (HTLV-I) or its integrated DNA sequences. Common features of this series of patients were an aggressive clinical course with poor response to treatment, high white blood-cell count, bone-marrow infiltration, splenomegaly, and chromosome abnormalities. Three patients had skin infiltration and one had hypercalcaemia. Immunological analysis showed a Thp (OKT4+) in all cases, and a heterogeneity, within the OKT4 population, of phenotypes and functional activities. Three patients had either HTLV-I integrated DNA sequences or anti-HTLV-I serum antibodies, or both. These patients had not received any blood transfusions, denied intimate contact with foreigners, and had always lived in small towns of central or southern Italy. Clinical and immunological findings in this series of patients suggest that both HTLV-I related and unrelated cases of Thp-CLL should be regarded as one disease arising from the same subpopulation of mature T-lymphocytes.
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PMID:T-helper phenotype chronic lymphocytic leukaemia and "adult T-cell leukaemia" in Italy. Endemic HTLV-I-related T-cell leukaemias in southern Europe. 286 33

A cytochemical study in samples from 100 lymphoid leukaemias, 84 of B-cell type and 16 of T-cell type, was carried out with three acid hydrolases: DAP IV, acid phosphatase (AP) and alpha-naphthyl acetate esterase (ANAE). DAP IV was studied in leukaemic T-cells both by cytochemistry and by a monoclonal antibody with the immunoperoxidase technique. Both methods showed similar results. AP and ANAE gave weak reactions in immature B-cell leukaemias (common-ALL and B-CLL) and were strongly expressed in plasma cell disorders. DAP IV showed no activity in any of the types of B-cell leukaemia studied and was strongly positive in some T-cell leukaemias but with a more restricted distribution than ANAE and AP. T-lymphoblasts (T-ALL) and mature (T8+) leukaemias were DAP IV negative. Within the T4+ malignancies DAP IV was positive in four T-prolymphocytic leukaemias, one of two T-CLL and one of three Sezary syndrome cases. Although DAP IV is strictly T-cell specific it does not appear to aid the differentiation between B- and T-cell disorders or the identification of T-cell subsets as determined by monoclonal antibodies. It remains to be established whether this enzyme will define a functionally distinct T-cell subset.
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PMID:Dipeptidylaminopeptidase IV (DAP IV) in B- and T-cell leukaemias. 286 56

Inosine monophosphate dehydrogenase (IMPD) is an important enzyme in de-novo purine synthesis. The level of IMPD activity has been suggested to determine whether acute leukaemia cells proliferate (if the activity is high) or differentiate (if IMPD activity is low). IMPD activity measured by the conversion of inosine monophosphate to xanthine monophosphate ranged from 12.5 to 87.0 (mean 49.4) pmol/h/10(6) cells in normal bone marrow. The levels were significantly raised in AML (range 14-374, mean 184 pmol/h/10(6) cells) and ALL (range 65-228, mean 172 pmol/h/10(6) cells). Normal tonsillar (B) lymphocytes showed higher levels (range 78-159, mean 110 pmol/h/10(6) cells) than resting peripheral blood T lymphocytes (range 8.8-51.2, mean 28.1 pmol/h/10(6) cells). In CLL, the results (range 19-173, mean 64.3 pmol/h/10(6) cells) were comparable to those of normal tonsillar B lymphocytes. IMPD levels could be related to cell cycle in PHA-stimulated lymphocytes, since IMPD activity increased in parallel with increase in DNA synthesis measured by labelled thymidine incorporation. On the other hand, IMPD activity did not correlate with the proportion of proliferating cells measured on a FACS sorter in either AML or ALL or in normal tonsillar B cells. We conclude that IMPD levels are higher in B than T lymphocytes and in acute leukaemia blasts compared to more differentiated mixed bone marrow cells. The results do not suggest, however, that IMPD assay will be of value in differentiation of the various subtypes of acute leukaemia or of malignant haemopoietic cells from the equivalent normal cell at the same level of differentiation.
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PMID:Inosine monophosphate dehydrogenase activity in acute leukaemia. 288 46

We have determined the prevalence of amplification and rearrangements for c-myc, c-myb, c-mos, bcr, c-abl, c-Ha-ras-1, c-N-ras, and c-K-ras-2 in a total of 51 cases of human leukaemia (19 patients with AML, 13 cases with CML, 14 cases with ALL, and 5 cases with CLL). Amplifications at a level of more than 2 two copies per haploid genome are apparently very rare and were found only once for c-myb in a c-ALL patient. Oncogene rearrangements were not found except for bcr, which was rearranged in all cases of CML, and 5 cases of ALL studied. Restriction fragment lengths polymorphisms (RFLPs) were also analysed. A previously described rare 5 kb EcoRI allele at the c-mos locus was absent in our patients. Rare alleles at the c-Ha-ras-1 locus were found to be significantly more prevalent in our patients than in a control group. Transfection experiments revealed no dominant transforming oncogenes in the tumour DNA of 3 patients carrying such rare alleles.
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PMID:Oncogene amplifications, rearrangements, and restriction fragment length polymorphisms in human leukaemia. 288 56

Cellular concentrations of dipeptidylpeptidases (DAP) II and IV were determined by fluorimetric assay in 152 cases of leukaemia and 24 permanent T-cell lines. Whilst its estimation appears to have few diagnostic applications, it was found that DAPII levels were generally higher in prolymphocytoid CLL variants (CLL-Pro) compared with "typical" CLL cases. Qualitatively, DAPII extracted from leukaemic B- and T-cells did not differ significantly with respect to molecular weight (Mr 82 kD: FPLC gel filtration) or substrate affinity (Km). Similarly, a single molecular weight species (Mr 189 kD) of DAPIV was also detected in all leukaemic sonicates examined although, in quantitative terms, increased DAPIV levels were primarily associated with a subgroup of CD4-positive postthymic malignancies. Studies of immature T-cell proliferations however indicated that DAPIV expression was unrelated to either stage of immunological differentiation or CD4 expression. No evidence of lineage restriction was found for either enzyme and it is concluded that variations in DAP cytochemical staining patterns reflect quantitative rather than qualitative differences.
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PMID:Quantitative and qualitative studies of leukaemic cell dipeptidylpeptidases II and IV. 289 26

We have reviewed literature data on 6,306 cases of hematological neoplasia--acute and chronic lymphatic and myeloid leukemias (CML excepted), myelodysplastic and chronic lymphoproliferative and myeloproliferative disorders, and malignant lymphomas--with the goal of quantitatively ascertaining how often cytogenetically unrelated clones occur in these diseases. Unexpectedly wide variations were found: in ANLL, unrelated clones were present in 1.1% of the 2,506 known cases with chromosome abnormalities characterized with banding technique; in the various myelodysplastic (MDS) and chronic myeloproliferative (CMD) disorders (total number of cases 1,299) the frequency was 4.3% and in lymphatic malignancies 1.3% (total case number 2,501). In the latter group the proportions varied between 0.4% and 0.6% in ALL and malignant lymphoma (ML) to as much as 6.2% in CLD and 7.3% in CLL. Some karyotypic abnormalities were encountered more often than would be expected from their general frequency in the various diseases. This discrepancy was particularly evident in MDS and CMD, where 5q- was found in slightly less and +8 in somewhat more than half of the 56 cases. Furthermore, these two aberrations were found as the only changes in the two coexisting clones in one-fourth of the material. Although if viewed in isolation these data would undoubtedly be best explained by assuming a multicellular origin of the neoplasm, it is entirely possible that what are cytogenetically perceived as unrelated clones could be subclones with some invisible aberration in common. If so, this interpretation indicates that changes like +8 and 5q-, both of which are common rearrangements in bone marrow neoplasms, are actually secondary changes that develop during tumor progression.
Leukemia 1989 Jan
PMID:Cytogenetically unrelated clones in hematological neoplasms. 290 9


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