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

Diagnostic features (cytochemistry, immunophenotyping and serum biochemistry) were examined in 51 cases of acute monocytic leukaemia (AMoL). Peroxidase, Sudan black B and alpha naphthyl acetate esterase (ANAE) cytochemical reactions were unrelated to morphological (FAB groups M5a and M5b) or immunological subtype. ANAE cytochemistry, however, indicated that AMoL cases could be subdivided into those with typical (M-type) reactions and those with insignificant staining or monocytic ANAE isoenzymes (defined by IEF). All cases were phenotypically CD13/CD33 positive and, with one exception, had greater than 30% HLA-DR positive cells. Membrane CD14 expression was insignificant or variable in 33% of M5a cases in contrast to 23/24 M5b cases which showed high proportions of CD14-staining cells with at least two monoclonal antibodies. Serum lysozyme, LDH and beta-2 microglobulin (beta 2m) were increased in 88%, 68% and 81% of cases respectively but, with the exception of statistically higher lysozyme levels in CD14+ cases, were unrelated to the morphological, cytochemical or immunological diagnostic subgroups. Clinical and diagnostic features were also examined as possible prognostic indicators. The morphological, cytochemical and immunological subgroups of AMoL were not found to be of prognostic relevance but age (P = 0.004), renal failure (P = 0.005) and serum beta 2m levels (P = 0.002) were related to patient survival. Moreover, renal failure and serum beta 2m remained significant (P = 0.012 respectively) when age was taken into account and were shown to be independent prognostic variables.
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PMID:Diagnostic and prognostic factors in acute monocytic leukaemia: an analysis of 51 cases. 329 31

A large number of monoclonal antibodies (McAbs) directed against components on myeloid (granulocytic/monocytic) cells have been generated. Individual McAbs were identified which are selectively reactive with antigenic determinants expressed by myeloid cells at specific stages of differentiation in a lineage-restricted fashion. The composite phenotype obtained by a combination of antimyeloid McAbs allows for a precise definition of the normal or malignant cell type under investigation. Cell binding studies on normal and leukemic cells and the biochemical characterization of the antigens provided the basis for a grouping of those antimyeloid McAbs into clusters of differentiation (CD). The reactivity patterns of CD11, CD13, CD14, CD15, and CD33 McAbs and the characteristics of the respective antigens are reviewed. These CD McAbs distinguish leukemic cells of myeloid from those of lymphoid origin. The monocytic nature of AML cells can be recognized by CD14 McAbs, whereas the other CD McAbs react with both monocytic and nonmonocytic types of acute myeloid leukemia. The expression of these differentiation antigens is not concordant with the morphological-cytochemical French-American-British (FAB) classification of leukemia; nevertheless, tendencies for agreement are apparent. If used in combination, FAB typing and immunophenotyping could provide complementary information. Their potential use for mapping of myeloid differentiation and for cell type recognition in leukemia phenotyping demonstrates the utility of antimyeloid CD McAbs for biological or clinical investigations. The diagnostic value of antimyeloid McAbs is enhanced if the reagents are included in a panel of McAbs standardized for routine immunophenotyping.
Leukemia 1987 Oct
PMID:Classification of acute myeloid leukemias--a comparison of FAB and immunophenotyping. 331 33

Two patients with acute nonlymphocytic leukemia (ANLL) (FAB-M4) and t(6;9)(p23;q34) are described. Immunological marker analysis revealed a phenotype of HLA-DR+/partly terminal deoxynucleotidyl transferase (TdT)+/CD13+ in both cases and CD33 positivity in one. The expression of CD13 and CD33 by TdT-positive cells was demonstrated by double immunofluorescence staining. Although it has been postulated that TdT plays a role in gene rearrangement, Southern blot analysis performed in one leukemia revealed that both the T cell receptor beta chain genes and the immunoglobulin heavy chain genes were in germ line configuration. Since we could not detect CD13+/TdT+ cells and CD33+/TdT+ cells in control bone marrow samples, double marker analysis was used to detect low numbers of residual leukemic cells during follow-up of one patient. A gradually increasing percentage of CD33+/TdT+ cells was detected in the bone marrow in a period of 6 months before hematological relapse. Although the t(6;9) may not be correlated to a specific French-American-British subtype, it may be associated with TdT-positive ANLL. Since TdT-positive ANLL seems to have a poor outcome, detection of TdT expression in ANLL patients is particularly important for diagnostic purposes. In addition, our results indicate that double immunological marker analysis for a myeloid marker and TdT allows detection of residual disease during follow-up.
Leukemia 1988 Mar
PMID:Translocation (6;9) may be associated with a specific TdT-positive immunological phenotype in ANLL. 334 92

The nature of the cells in 21 cases of acute leukaemia with blasts which were undifferentiated by light microscopy criteria was investigated by immunophenotyping, ultrastructural cytochemistry and DNA analysis. Two groups of cases were recognized. Fourteen cases were negative with B and T lymphoid markers and expressed one or two myeloid antigens detected by the monoclonal antibodies (McAb) MCS2 (CD13) and MY9 (CD33). Peroxidase activity was demonstrated at ultrastructural level by the method of Roels on unfixed cells in eight out of 10 cases; rearrangement of the immunoglobulin (Ig) genes was demonstrated in one of the three cases investigated. These cases are proliferations of early, MO, myeloblasts which can only be recognized by immunological and ultrastructural cytochemical methods. The remaining seven cases revealed a complex phenotype with expression of myeloid and lymphoid antigens. Peroxidase activity was detected in blasts from two cases with rearrangement of the Ig-heavy chain gene; in one of them the T cell receptor beta and gamma chain genes were also found in rearranged configuration. This group comprises cases of biphenotypic and mixed acute leukaemia which probably involve multipotent stem cells. This study demonstrates that the expression of myeloid antigens on blast cells parallels closely the presence of peroxidase activity and that lymphoid markers correlate with gene rearrangements at DNA level. Our findings are reassuring with respect to the specificity of the antimyeloid McAb for the diagnosis of cases which are unclassifiable by conventional methods.
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PMID:The role of ultrastructural cytochemistry and monoclonal antibodies in clarifying the nature of undifferentiated cells in acute leukaemia. 339 Mar 93

Murine L1210 leukemia cells resistant to the antineoplastic agent L-phenylalanine mustard have a 1.5-2.0-fold elevation in their cellular GSH and GSSG content as compared to drug-sensitive cells. Cellular uptake of L-[U-14C]cystine and its incorporation into GSH of the resistant tumor are correspondingly elevated. Synthesis of gamma-glutamylcysteine, GSH, and GSSG is elevated 1.5-2.0-fold in cell-free preparations of the resistant tumor. This increased synthesis of GSH is attributed to increased cellular content (1.6-fold) of gamma-glutamylcysteine synthetase. GSH synthetase activity is equivalent in both drug-sensitive and -resistant cells. Investigation into the hydrolysis of selected peptides by cell-free preparations of both sensitive and resistant tumors suggest that aminopeptidase M participates in the formation of L-cysteine from L-Cys-Gly. This is supported by the observation that these preparations readily degrade L-Leu-p-nitroanilide and L-Ala-L-Ala-L-Ala, known substrates for aminopeptidase M, but not dipeptidase. The failure of the tumors to degrade Gly-D-Ala, a dipeptidase substrate, and the marked inhibition of L-Ala-Gly, L-Cys-Gly, and L-Ala-L-Ala-L-Ala hydrolysis by Bestatin further support a role for aminopeptidase M in the generation of L-cysteine from L-Cys-Gly. These results suggest that the drug-resistant tumor cell has developed an efficient mechanism for maintenance of elevated GSH which involves both gamma-glutamyl transpeptidase-initiated catabolism of GSH to cysteine and its reutilization by gamma-glutamylcysteine synthetase.
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PMID:Elevation of glutathione in phenylalanine mustard-resistant murine L1210 leukemia cells. 366 23

A metastatic variant cell subline of the Abelson virus-transformed murine large lymphoma/lymphosarcoma RAW117 has been selected in vivo ten times for liver colonization. Highly metastatic subline RAW117-H10 forms greater than 200 times as many gross surface liver tumor nodules as the parental line RAW117-P. Analysis of cellular proteins and glycoproteins indicates reduced expression of murine Moloney leukemia virus-associated p15, p30, and gp70, and increased expression of a sialoglycoprotein, gp150, in the highly metastatic H10 cells. Northern analyses of oncogene expression suggested that mRNA of various oncogenes was expressed equally or not expressed in the RAW117 cells of differing metastatic potential. Differential gene expression was examined using a cDNA library of 17,600 clones established from poly A+ mRNA isolated from H10 cells. The cDNA library was screened by the colony hybridization technique using probes made from both RAW117-P and -H10 cells. Approximately 99.5% of these cDNA clones were expressed identically in P and H10 cells. Of the few differentially expressed cDNA clones (approx. 150/17,600), one-half of these were identified as Moloney leukemia virus sequences in a separate probing with a radiolabeled Moloney leukemia virus probe. The remainder of the differentially expressed mRNA detected by colony hybridization of the cDNA library were expressed at higher levels (approx. 1/6) or lower levels (approx. 1/3) in the highly metastatic H10 cells.
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PMID:Differential expression of metastasis-associated cell surface glycoproteins and mRNA in a murine large cell lymphoma. 376 37

Rauscher leukaemia virus (RLV), extensively purified by rate and density gradient centrifugation procedures, exhibited aminopeptidase (AP) activity. The amount of virion activity was about 0.005 times the specific activity of purified hog kidney aminopeptidase M (EC 3.4.11.2). The activity was also found in purified Moloney and Gross leukaemia viruses, but not in comparable gradient fractions of uninfected JLSV-9 cells. Furthermore replacement of serum by bovine serum albumin in the growth medium of virus producing cells did not affect the AP activity. These results indicate that murine leukaemia viruses (MuLV) possess a tightly bound AP activity which is present as a minor component of the virion preparation and is probably not due to host cell membrane or serum contamination. Characterization of the pH optimum and substrate specificity show the MuLV aminopeptidase activity is similar to but different from both hog kidney, leucine aminopeptidase (EC 3.4.11.1) and aminopeptidase M (EC 3.4.11.2).
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PMID:Aminopeptidase activity associated with purified murine leukaemia viruses. 677 35

In the past, studies on CD34+ cells have been based on the use of monoclonal antibodies conjugated with different fluorochromes that show different fluorescence intensity and yield variable results. Moreover, most of these studies have neither specifically focused on adult human BM samples nor have they used combinations to explore specifically the phenotype of myeloid committed CD34+ cells. The aim of the present study has been to characterize the normal human CD34+ precursor cells from adult BM in order to identify missing or extremely rare phenotypes that can be used for detecting minimal residual disease (MRD) in patients with AML. For this purpose we have utilized the fluorochrome conjugates that provide the most sensitive signals for identifying low antigenic expression, and the technique has been adapted to the characterization of cells present at very low frequencies. Normal human BM samples from 13 adult healthy volunteers have been analyzed using triple stainings at flow cytometry. The mean percentage of CD34+ cells detected was 0.72 +/- 0.33%; these cells displayed an heterogeneous light-scatter distribution. Most CD34+ cells coexpressed CD38 (96.7 +/- 5.7%), HLADR (81.6 +/- 14.0%), CD33 (84.7 +/- 18.3%), CD13 (84.6 +/- 16.2%) and CD71 antigens (65.5 +/- 9.1%). In addition, almost half of CD34+ cells were CD117+ (60 +/- 26.8%). Only a small proportion of CD34+ cells coexpressed CD4 (15.5 +/- 11.7%, CD36 (31.7 +/- 6.2%), CD61 (16.3 +/- 12.9%), CD41 (6.5 +/- 5.5%) or the lymphoid associated markers CD10 (18.6 +/- 11.8%) and CD19 (12.3 +/- 13.2%). Reactivity for the CD15 antigen was observed in a small population of CD34+HLADR+ cells (11.6 +/- 11.2%) although its intensity of expression was lower than that of the more mature granulocytic cells. No CD34+ cells displayed CD14, CD65, CD20, strong CD22, CD3 and CD56 antigens. Accordingly, most adult bone marrow CD34+ cells appeared to be committed to the myeloid lineage (CD13+/CD33+) and displayed an intermediate-to-large FSC/SSC while the lymphoid-committed CD34+ cells (CD19+, CD10+) were in a minority with low FSC/SSC values. By triple marker stainings several phenotypes of CD34+ precursor cells were found to be either undetectable or present at very low frequencies (< 1 x 10(-3)) in the normal human adult bone marrow. These data may be of great value for defining leukemia 'associated' phenotypes used to detect minimal residual disease in adult acute leukemia patients.
Leukemia 1995 Nov
PMID:Phenotypic analysis of CD34 subpopulations in normal human bone marrow and its application for the detection of minimal residual disease. 747 81

Of 235 consecutive patients with de novo acute myeloid leukemia (AML), clonal chromosomal abnormalities were detected in 151 (64%) of them. Twenty-four of the 71 patients with M2 AML had t(8;21), 35 of the 36 M3 patients had t(15;17), and 11 of the 45 M4 leukemia disclosed inv(16). Six of the eight patients with 11q23 abnormality had M4 or M5 subtype of leukemia. The incidence of t(15;17) and t(8;21) was higher in our patients than in patients from most Western countries. Immunophenotyping was performed on 197 patients. Patients with t(15;17) were associated with negativity to HLA-DR, CD11b, and CD34. Patients with t(8;21) expressed CD13 and CD33 less frequently than other patients, but all showed CD15 positivity. Coexpression of lymphoid-associated antigens on the leukemic blasts was detected in 52 patients (26%), including all 7 patients with t(9;22), 3 of the 8 patients with t/del(11)(q23), 2 of the 25 patients with t(15;17), and 2 of the 22 patients with t(8;21). Seven (35%) of the 20 patients coexpressing lymphoid markers showed immunoglobulin heavy chain or T-cell receptor beta-chain gene rearrangements, while only 2 (4%) of the 53 patients without lymphoid antigen expression did so. Patients with inv(16), t(8;21), and t(15;17) had a better prognosis than other patients. Of all surface antigens tested, only CD15, CD11b, and HLA-DR were of prognostic value: CD15 with a higher complete remission (CR) rate and CD11b or HLA-DR with a shorter CR duration. N-ras mutations were detected in 7 (18%) of the 40 patients in the study, including two of the three patients with inv(16). This study demonstrated differences in clinical features, immunophenotypes, and genotypes among different cytogenetic subgroups.
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PMID:Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia. A study of 235 Chinese patients in Taiwan. 749 45

The effects of six recombinant human cytokines: erythropoietin, GM-CSF, G-CSF, interleukin-3, -4 and -6 on the proliferation and differentiation of a human multilineage myeloid leukemia cell line MHH 225, established from the bone marrow of an AML(M7) patient in our laboratory determined by changes in antigen expressions using monoclonal antibodies in APAAP technique were examined in liquid suspension culture. The MHH 225 cells have been growing exponentially without cytokines or conditioned media. About 90 per cent of MHH 225 cells are CD33+ CD34+ CD3- CD7- CD19- CD20- TdT- with 57.6 per cent, 28.3 per cent and 7.8 per cent of them being CD41+, glycophorin A+ and CD15+, respectively. After five days of treatment with erythropoietin, GM-CSF, G-CSF or IL-6 no change was observed in MHH 225 cell antigens expression. IL-3 (100 U/ml) induced a moderate increase in only CD13 and alpha naphthyl esterase positive cells from 6.5 +/- 1.9 per cent and 5.7 +/- 2.4 per cent in control cultures to 21.6 +/- 3.0 per cent and 19.1 +/- 2.8 per cent, respectively. On the other hand, 100 U/ml IL-4 significantly increased the number of CD13, CD15 and alpha naphthyl esterase positive cells to 48.9 +/- 5.0 per cent, 47.2 +/- 3.6 per cent and 46.1 +/- 3.0 per cent, p < 0.001, respectively. Also, 100 U/ml IL-4 decreased the number of CD41 positive cells from 57.6 +/- 2.8 per cent to only 25.9 +/- 3.6 per cent and did not change the number of CD33 or glycophorin A positive cells. The present results showed that out of the six myelopoietic growth factors tested, IL-4 was the only one to inhibit selectively the proliferation of CD33+ CD41+ leukemic megakaryoblast cells suggesting that IL-4 may have a lineage regulatory effect in favour of a myeloblastic CD33+ CD13+ CD15+ at the expense of a megakaryoblastic CD33+ CD41+ amplification in human leukemia cells and with apparently no effect on leukemic erythroblast cells. The MHH 225 cell line provides a useful tool and freely available model to scientists for studying signal transduction via IL-4 and for studies of 'lineage switch'.
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PMID:Interleukin-4 inhibits proliferation of human leukemic megakaryoblast cell line MHH 225. 752 Aug 82


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