Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytogenetic studies were made on 160 patients with acute nonlymphocytic leukemia (ANLL) between 1963 and 1979, of whom 115 had acute myelocytic leukemia with 67 patients showing aneuploidy (58.3%). Among these, 24 patients were found to have similar chromosome alterations that appeared to involve specifically chromosomes 8 and 21. Banding studies on at least 7 of these patients confirmed the presence of a translocation between these two chromosomes. Of 160 ANLL patients, 142 were scored for neutrophil alkaline phosphatase (neutrophil AP) at the time of diagnosis. Fifty-nine patients showed a low neutrophil AP score, 42 a normal value, and 41 a high value. All patients with 8;21 (or C/G) translocation had a low neutrophil AP score and leukemic cells with maturation (M2 of FAB classification) in the bone marrow. In vitro liquid culture for 2 wk of 8;21 translocated leukemic cells revealed no increase of neutrophil AP activity nor increase of mature granulocytes, whereas 9;22 translocated chronic myelocytic leukemia cells with a low neutrophil AP score did so. Neutrophil AP score at the time of diagnosis in acute myelocytic leukemia is very useful for detecting 8;21 translocation AML and for studying the pathophysiology and genetic alterations of the characteristic subgroup of AML with 8'21 translocation.
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PMID:In vivo and in vitro activity of neutrophil alkaline phosphatase in acute myelocytic leukemia with 8;21 translocation. 694 48

Expression of P-glycoprotein (PGP), the product of the multi-drug resistance mdr1 gene was studied by immunocytochemistry on bone marrow slides using JSB1 monoclonal antibody and the alkaline phosphatase-antialkaline phosphatase (APAAP) and avidin-biotin-peroxidase (ABC) techniques in 82 cases of untreated myelodysplastic syndromes (MDS), of whom ten had evolved to AML (MDS-AML). The relationship between PGP expression, myeloperoxidase activity and immunophenotype of blast cells, karyotype and outcome was also analyzed. PGP expression was found in the blasts of 34 of the 82 patients (41%), the majority of blasts being stained in positive cases. PGP positivity was rare in 'low risk' MDS (RA and RARS: 2/12 cases) as opposed to 'high risk' MDS (RAEB, RAEB-T, CMML: 25/60 cases) and MDS-AML (7/10 cases) (p = 0.04). PGP expression was positively correlated to the presence of myeloperoxidase activity in less than 3% of blasts (p = 0.025), and CD34 antigen expression (p = 0.04), whereas CD33 antigen expression had borderline significance (p = 0.07), demonstrating that PGP expression predominated in blasts with an immature phenotype. An abnormal karyotype, and especially the presence of monosomy 7, was not correlated to a higher incidence of PGP expression, however. There was a trend for more frequent progression to AML and for shorter survival in PGP-positive cases, but differences with PGP-negative cases were not significant. Twenty patients received intensive anthracycline-Ara-C chemotherapy and ten (50%) achieved complete response, including 9/13 (69%) PGP-negative cases and 1/7 (14%) PGP-positive cases (p = 0.03). Twenty other patients were treated with low-dose Ara-C and ten (50%) responded (complete or partial response). PGP-positivity did not negatively affect response to low-dose Ara-C: 4/11 responses in PGP-negative, and 6/9 responses in PGP-positive patients (p = 0.18). Because the treatment choice in advanced MDS (especially between anthracycline-Ara-C or low-dose Ara-C, chemotherapy) is difficult, our preliminary therapeutic results suggest that the analysis of PGP expression could have practical importance in MDS. These findings however, will have to be confirmed on larger numbers of patients. Clinical trials using drugs potentially reverting mdr, activity could also be warranted in MDS.
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PMID:Expression of the multidrug resistance P-glycoprotein and its relationship to hematological characteristics and response to treatment in myelodysplastic syndromes. 751 32

We investigated the prognosis value of CD34 and P-170 expression in blast cells of adult patients affected by de novo acute myeloid leukemia (AML). CD34 antigen was analyzed by indirect immunofluorescence (IFI) and alkaline phosphatase-labeled streptavidin biotine (AP-LSAB) in 62 patients (median age: 51 years). P-170 expression was determined by AP-LSAB in 51 cases using JSB1 and C219 monoclonal antibodies. All patients were treated with conventional chemotherapy induction regimen. Follow-up was from 6 to 79 months. Complete remission (CR) rate was not statistically different between CD34+ and CD34- patients (67 vs. 84%, p = 0.2). The duration of CR and survival were not influenced by CD34 expression. Karyotype abnormalities were more frequent among MDR+ patients (65 vs. 21%, p < 0.01). CR rate was statistically lower in MDR+ patients as compared to MDR- patients (63 vs. 96%, p = 0.01). Median disease-free survival (DFS) was shorter for MDR+ patients but the difference was not significant (5 vs. 10 months, p = 0.09). Patients who were positive for both parameters CD34 and P-170, had a poor prognosis with a 50 vs. 100% CR rate for CD34/P-170 negative patients, (p = 0.002), a lower median DFS (3 vs. 12 months, p = 0.01) and overall survival (OS) (3 vs. 14.5 months, p = 0.01). Results of cytogenetic analysis did not influence CR rate but the relapse rate was higher, although not significant, for the patients with unfavorable karyotype (63 vs. 33%). The seven CD34+/MDR+ patients with poor prognosis karyotype had a statistically lower CR rate, median DFS and OS than the 7 CD34-/MDR- patients with normal or favorable karyotype (CR: 29% vs. 100%, p = 0.02), (DFS: 3 vs. > 12 months, p = 0.01), (OS: 4 vs. > 12 months, p = 0.02). Our data indicate that P-170 but not CD34 expression is predictive for a lower CR rate. The identification of a bad prognosis subgroup of CD34+/MDR+ AML patients (and especially those with poor prognosis karyotype) has to be confirmed on larger series using uniform methodology.
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PMID:P-glycoprotein (P-170) and CD34 expression in adult acute myeloid leukemia (AML). 752 90

We have adapted the alkaline phosphatase-anti alkaline phosphatase (APAAP) technique to demonstrate cell antigen distributions in intact agar culture. The method facilitates batch processing and is no less convenient to perform than standard APAAP procedures. Myeloid and lymphoid antigens generally demonstrated strong staining intensity. However, staining at day 0 consistently produced no antigen expression for two monoclonals (CD11c and CD34) in contrast to positivity in parallel cytospins. CD11c showed rapidly increasing antigen expression over subsequent days of culture whereas the expression of CD34 could not be shown in conventional agar culture at any time from day 0 to day 14. Positivity was only restored in CD34-positive leukaemic cells using a modified culture technique in which cells were cultured as pre-formed small aggregates. Assessment of these aggregates extended to cell cycle analysis using anti-bromodeoxyuridine. CD71 positivity in normal culture samples correlated with colony configuration (whether clones were 'spread' or 'tight' in appearance). CD38 staining of normal bone marrow culture at day 7 showed asymmetrical staining of cells in a small number of micro-groups. The clonal detection of aberrant antigens (CD7, CD2) for assessment of minimal residual disease in AML was a disappointment due to the relative frequency of positive clones in normal culture.
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PMID:Immunostaining of whole agar cultures by APAAP. 762 32

Terminal deoxynucleotidyl transferase (TdT) was initially considered as a marker of immature lymphoid cells, but many studies have since provided conclusive evidence for the existence of TdT+ cases of acute myeloid leukemia (AML). The reported incidence of TdT+ AML cases varies largely (from 0% to 55%, average of combined data of the literature 18%, children 19%, and adults 21%) suggesting interlaboratory differences in the types of AML examined, the sensitivity of the method used, and the percentage of positive blasts taken as cut-off value. Significantly higher frequencies of TdT+ AML were reported in studies employing immunocytochemical staining (alkaline phosphatase anti-alkaline phosphatase or immunoperoxidase) than in series using immunofluorescence microscopy or biochemical assays. Statistical analysis of various cut-off levels demonstrates an inverse correlation between cut-off point and incidence. The combined data show that TdT-positivity is more common in the immature cell types (M0, M1), with no correlation with age or sex. Except for contested suggestions of an association with t(6;9) and t(8;21), no clear relationship between karyotype and TdT status has been documented. Although an association between T-cell receptor or immunoglobulin gene rearrangements and expression of TdT in AML was postulated, subsequent studies could not demonstrate this correlation. There was no significant relationship with other immunophenotypic markers except for CD34 positivity suggesting that the TdT+ cells represent an immature population. The percentage of positive cells was usually lower in AML than in ALL; in most cases only a subpopulation of the AML cells was TdT+. Thus, TdT could be viewed as a marker of hematopoietic immaturity. In about one-half of the studies on adults, TdT expression was reported to indicate a poor prognosis; others did not find any prognostic difference between TdT+ and TdT- AML cases. No correlation between TdT-positivity and prognosis was found in childhood AML.
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PMID:Terminal deoxynucleotidyl transferase (TdT) expression in acute myeloid leukemia. 768 37

The authors describe a combination technique enabling detection of in situ hybridization (ISH) signals from chromosome-specific probes in interphase or mitotic cells that still retain the alkaline phosphatase antialkaline phosphatase (APAAP) or Sudan black B (SBB) staining reactions (simultaneous detection) or have been first classified morphologically and then by APAAP or SBB. The technique can be used on cell suspensions, in situ cultures and tissue sections. Examples from leukemias (chronic lymphocytic, myeloid, and acute myeloid leukemia) and solid tumors (chondromyxoid fibroma and glioblastoma) illustrate the potential of the technique in investigation of cancer tissue heterogeneity. In leukemias, it can be used to study cell lineage involvement, stem cells, and minimal residual disease, as well as to monitor therapy. In solid tumors, it can be used to identify neoplastic areas of tissue and to track the site of origin of neoplastic cells. Finally, it can be used to study the significance of chromosome abnormalities in carcinogenesis.
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PMID:Analysis of phenotype and genotype of individual cells in neoplasms. 768 32

Anti-P-glycoprotein monoclonal antibody JSB-1 and alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunocytochemical staining technique were used to study the relation between P-glycoprotein expression and clinical multidrug resistance (MDR) in 42 patients with acute leukaemia (23 ALL and 19 ANLL). 10 of 17 patients who were diagnosed as refractory or relapsed acute leukaemia were positive with P-glycoprotein expression, while only 3 of 14 newly diagnosed and 1 of 11 who were in complete remission were positive. The preliminary results indicated that there was a close association between the P-glycoprotein expression and the clinical resistance to chemotherapy in some patients.
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PMID:[Detection of P-glycoprotein expression in patients with acute leukaemia and clinical significance]. 771 12

Inositol 1,4,5-triphosphate (IP3) and inositol 1,3,4,5-tetrakisphosphate (IP4) are calcium-regulating second messenger molecules generated following the binding of a wide range of hormones and growth factors to their receptors. The actions of these messengers, which play important roles in the regulation of cell proliferation as well as in other signaling pathways, are terminated by the action of a 5-phosphomonoesterase (5-PME) enzyme. We have assayed this enzyme in normal and malignant hemopoietic cells. Extracts from normal bone marrow cells and peripheral blood mononuclear cells (PBMNC) degraded [3H]IP3 at rates of 74.5 (+/- 3.4) and 84.5 (+/- 7.9) pmol/min/micrograms protein, respectively. PME activity in 10/13 (77%) acute lymphoblastic leukemia samples were significantly below the normal range and the enzyme was completely undetectable in three (23%) of these. Enzyme activity in 8/9 (89%) chronic lymphocytic leukemia samples were below the normal range, being undetectable in three of these (33%). Nine of 24 (38%) acute myeloid leukemia samples contained low 5-PME levels, which was undetectable in one sample. Reduced 5-PME activity was detected in 2/7 (28%) of chronic granulocytic leukemia samples. The data here are consistent with the hypothesis that a reduced rate of degradation of IP3 and IP4 in some leukemia cells may result in the aberrant operation of signaling pathways, possibly including those involved in the control of cell proliferation.
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PMID:Inactivation of calcium ion-regulating inositol polyphosphate second messengers is impaired in subpopulations of human leukemia cells. 793 69

Eleven patients with acute myeloid leukemia (AML) were studied with a technique that simultaneously identifies cytogenetic abnormality and immunophenotype of the same mitotic cell. To determine the cell lineages with abnormal karyotypes, monoclonal antibodies in the alkaline phosphatase-antialkaline phosphatase (APAAP) detection procedure were used. The granulocytic/monocytic lineage was involved in the leukemic process in all 11 patients. In nine patients, we also detected abnormal karyotypes in the erythrocytic and/or megakaryocytic lineages. All four patients with secondary AML showed involvement of the granulocytic/monocytic, erythrocytic, and megakaryocytic lineages into the leukemic process, as compared with five of seven patients with de novo AML. One patient with trisomy 8 showed erythrocytic participation in the leukemic process, but in another the erythrocytic lineage had only normal karyotypes. Thus, in AML, the chromosome abnormalities apparently usually originate at the multipotent progenitor cell stage, since in addition to granulocytic/monocytic lineages, erythrocytic and/or megakaryocytic lineages were also involved. Some patients show involvement of granulocytic/monocytic lineages only, however, suggesting that the target cell belongs to a more mature committed progenitor cell stage.
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PMID:Immunophenotype of mitotic cells with clonal chromosome abnormalities demonstrating multilineage involvement in acute myeloid leukemia. 822 5

We report two additional patients with acute myeloid leukemia (AML) and a translocation between chromosomes 7 and 11: t(7;11)(p15;p15). One patient was diagnosed as having AML-M2 and the other as AML with myelofibrosis. Both patients had low-level neutrophil alkaline phosphatase (NAP) scores. In the literature, only 15 AML patients with t(7;11)(p15;p15) have been reported; nine of them had an AML-M2 morphology, and all had a decreased NAP score. Moreover, mean survival of the reported AML patients with t(7;11)(p15;p15) was 15 months, although 85% of them obtained complete remission, indicating that this type of leukemia frequently tends to relapse. These findings indicate a strong association between the chromosome abnormality and hematologic manifestations of this disease.
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PMID:Two additional cases of acute myeloid leukemia with t(7;11)(p15;p15) having low neutrophil alkaline phosphatase scores. 835 6


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