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)

Expression of CD34 by leukemic blasts was analyzed in 230 pediatric and 251 adult patients with de novo AML enrolled in two large multicenter trials (AML-BFM-87 and AMLCG respectively). The association between CD34 positivity and morphological classification according to FAB criteria, cytogenetic aberrations, immunophenotypic features and clinical characteristics was investigated. CD34 was expressed (> or = 20%) by leukemic cells from 45% of childhood and 43% of adult AML patients. CD34+ AML was often associated with M1/M2 morphology as well as the coexpression of CD7 and TdT. Translocation t(8;21), inv(16) and chromosome 5 and 7 aberrations were more frequently observed in CD34+ AML. There was a low frequency of CD34 expression in infant AML but no age dependency was evident in adult patients. CD34 expression exerted no influence on the rate of complete remissions (CR) after intensive multidrug induction therapy. In adults, 56% of the CD34-positive and 64% of CD34-negative cases achieved CR (P = 0.29), and the childhood trial even revealed a slight advantage for CD34+ AML with a CR rate of 80% vs. 71% for CD34-negative cases (P = 0.068). Long-term follow-up disclosed no significant differences in remission duration or event-free survival between the CD34-positive and CD34-negative groups. In conclusion, CD34+ AML patients comprise a heterogeneous group with good as well as poor risk factors. Though characterized by some distinct features, CD34 lacks prognostic significance in de novo AML patients submitted to intensive polychemotherapy.
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PMID:Clinical, morphologic, cytogenetic and prognostic implications of CD34 expression in childhood and adult de novo AML. 754 32

From the public health standpoint, acute myeloid leukemia (AML) is an important problem for both young and older adults. AML is the leading cause of cancer death in men aged 15-34 years and the second leading cause of cancer death in women in this age group. This clearly has an impact on loss of life in the productive years. But in terms of the population most affected and of the biology of the disease, the impact is even greater for the elderly patient. Age has been established in many AML treatment trials as a poor prognosis factor. Although ther is no consensus as to what age defines an elderly AML patient, those older than 45 years have a lower complete remission (CR) rate than those who are younger. In patients younger than 50 years, the average CR rate is 60%-75%; in contrast, in patients older than 70 years, the CR rate is 35%-40%. Long-term disease-free survival ranges from 25% to 50% in adult AML, depending on the post-remission therapy used and the age of the patient. In November 1991, the Southwest Oncology Group began a study to address the problems of treating AML in the elderly. Many previous treatment trials of AML have included elderly patients as a subgroup of the study analysis, with a larger proportion of young patients. This trial was designed to test the hypothesis that a myeloid growth factor used as supportive care could improve the outcomes in elderly patients with AML.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Design and conduct of a double-blind, placebo-controlled trial of daunorubicin and cytarabine with or without granulocyte colony-stimulating factor in elderly patients with acute myeloid leukemia: a Southwest Oncology Group study. 757 2

Ara-C is currently used in the treatment of adult acute myeloid leukemia (AML). The cytotoxicity of Ara-C derives from an inhibition of DNA synthesis which can be determined using flow cytometry from the amount of bromodeoxyuridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrd/DNA. A resistance index (RI) was expressed as the ratio of the amount of BrdUrd incorporated into S phase cells incubated with Ara-C to that incorporated in the absence of Ara-C. In Ara-C sensitive and resistant HL60 cell lines, a linear relationship between RI and log Ara-C concentration was observed. This technique was applied to 96 bone marrow samples from patients with de novo AML treated by a regimen containing Ara-C. A first group of nine patients with high RI values included only drug resistant (DR) patients; a second group of 63 patients with low RI values included 62 patients who achieved a complete remission (CR); a third group of 24 patients with intermediate RI values included 19 CR and five DR patients. In view of these results, we think that it is possible to detect a majority of DR patients treated by Ara-C.
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PMID:[Detection of the resistance to Ara-C blast cells in acute myeloid leukemia using flow cytometry]. 762 42

We have investigated the self-renewal capacity (PE2) and in vitro sensitivity to cytosine-arabinoside (ara-C) and daunorubicine (DNR) of leukemic progenitors (CFU-AML) to determine the significance of these tests for predicting induction treatment outcome in 75 adult acute myeloid leukemia (AML) patients. In addition, in a part of this group of patients (n = 46) we determined the expression of P-glycoprotein (P-gp) immunocytochemically and correlated those results with the therapeutic response. We have evaluated 66 patients who showed the following responses: 28/66 complete remissions (CR), 16/66 resistant leukemias (RL) and 22/66 early deaths (ED). The PE2 value was significantly higher in patients with RL than in patients with CR (p < 0.00375). CFU-AML sensitivity to ara-C and DNR alone was not different between response groups, but the difference in CFU-AML sensitivity to the combination of drugs between patients with CR and RL was not significant, although a trend was noted (p < 0.06). P-gp expression was found in only 1/18 patients who achieved CR but in 9/11 patients with RL and 7/11 patients with ED, which is a highly significant difference (p < 0.0006). We concluded that both PE2 and P-gp expression in AML cells are valuable predictors of therapeutic response in adult AML and should be included in creating the best therapeutic approach to AML patients.
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PMID:In vitro drug sensitivity of leukemic progenitors and P-glycoprotein expression in adult acute myeloid leukemia: correlation with induction treatment outcome. 762 94

The clinicopathological features and the prognostic significance of acute myeloid leukaemia (AML) with trisomy 11 are currently unknown. In this study we describe 15 adult AML cases with trisomy 11. Trisomy 11 was the sole chromosomal anomaly in eight cases; the remaining seven cases were characterized by +11 in association with other karyotypic aberrations. Patients ages ranged from 34 to 79 years. 12 patients were male; three were female. Although there was no correlation of trisomy 11 with any specific FAB subgroup [M2 (n = 7), M1 (n = 5), M4/5 (n = 2), M3 (n = 1)] less mature forms predominated. Immunologically, the leukaemic blasts showed a strikingly consistent stem cell phenotype with expression of HLA-DR, CD34 and the myeloid antigens (CD15, CD33 and/or CD13). In addition, two cases expressed the B-cell associated antigen CD19. The presence of trilineage dysplasia, suggesting the presence of an underlying myelodysplasia (MDS), was observed at presentation in five cases; in another case MDS was evident at relapse only. Unexpectedly, MLL gene rearrangements were observed in two of four cases characterized by trisomy 11 as the sole karyotypic abnormality; however, MLL aberrations were not identified in three cases with trisomy 11 accompanied by other karyotypic anomalies. The majority of patients in each subgroup (i.e. those with and without additional cytogenetic abnormalities) achieved a short first complete remission (CR) (mean 8 months) and failed to obtain a second CR. Only one patient in each trisomy 11 subgroup is in a continuous CR for > 34 months. These findings suggest that trisomy 11 leukaemia is characterized by a stem/progenitor cell immunophenotype with poor response to standard chemotherapeutic regimens and an unfavourable prognosis.
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PMID:Trisomy 11: an association with stem/progenitor cell immunophenotype. 779 46

The topoisomerase (topo) II-directed agents etoposide, daunorubicin (DNR), and amsacrine (m-AMSA) are widely used in the treatment of acute myelogenous leukemia (AML). In the present study, multiple aspects of topo II-mediated drug action were examined in marrows from adult AML patients. Colony-forming assays revealed that the dose of etoposide, DNR, or m-AMSA required to diminish leukemic colony formation by 90% (LD90) varied over a greater than 20-fold range between different pretreatment marrows. Measurement of nuclear DNR accumulation in the absence and presence of quinidine revealed evidence of P-glycoprotein (Pgp) function in 8 of 82 samples at diagnosis and 5 of 36 samples at first relapse, but the largest quinidine-induced increment in DNR accumulation (< 2-fold) was too small to explain the variations in drug sensitivity. Restriction enzyme-based assays and sequencing of partial topo II alpha and topo II beta cDNAs from the most highly resistant specimens failed to demonstrate topo II gene mutations that could account for resistance. Western blotting of marrow samples containing greater than 80% blasts revealed that the content of the two topo II isoenzymes varied over a greater than 20-fold range, but did not correlate with drug sensitivity in vitro or in vivo. In addition, levels of topo II alpha and topo II beta in 46 of 47 clinical samples were lower than in human AML cell lines. Immunoperoxidase staining showed that these low topo II levels were accompanied by marked cell-to-cell heterogeneity, with topo II alpha being abundant in some blasts and diminished or absent from others. There was a trend toward increasing percentages of topo II alpha-positive cells in pretreatment marrows that contained more S-phase cells. Consistent with this observation, treatment of patients with granulocyte-macrophage colony-stimulating factor for 3 days before chemotherapy resulted in increases in topo II alpha-positive cells concomitant with increases in the number of cells traversing the cell cycle. These observations have implications for the regulation of topo II in AML, for the use of topo II-directed chemotherapy, and for future attempts to relate drug sensitivity to topo II levels in clinical material.
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PMID:Topoisomerase II levels and drug sensitivity in adult acute myelogenous leukemia. 790 87

During 1971-1988, 194 adults with de novo acute myeloid leukemia (AML) received initial therapy at the University of Minnesota with an anthracycline-based regimen. Seventy-two of the 194 required further chemotherapy and received a second cycle of the same or similar therapy; 63 of these 72 were evaluable. For each marrow, a tumor burden index (TBI) was calculated, as the product of the marrow cellularity and the proportion of malignant cells. For each patient, the decrement in TBI between the initial and day approximately 14 marrows was recorded. Patients who achieved second-cycle CR were comparable to those who did not in general descriptors; there was no difference between second-cycle CR achievers and nonachievers in the cytoreduction effected by the initial cycle of therapy (74.9% +/- 4.5% [sigma] versus 71.9% +/- 5.9%). We then stratified patients according to the first-cycle cytoreduction, asking if we could find a level that was reliably predictive of increased or decreased likelihood of achieving CR with cycle 2. We could not, despite testing at many centile cuts. Patients achieving a very "poor" degree of cytoreduction in cycle 1 were as likely to achieve CR with cycle 2 as were patients having a very "good" initial cytoreduction. We conclude that (1) first-cycle response is not a useful predictor of second-cycle outcome in anthracycline-based therapy of de novo adult AML; and (2) a "poor" response to cycle 1 does not therefore a priori indicate a change to a different regimen for cycle 2.
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PMID:Anthracycline-based therapy of de novo acute myeloid leukemia in adults: failure of first-cycle cytoreduction to predict second-cycle outcome. 794 80

Cytarabine (Ara-C) is currently used in the treatment of adult acute myeloid leukemia (AML). To predict the results of induction chemotherapy, it could be useful to detect leukemic cells that are resistant to Ara-C in patients with AML. Using a bromodeoxyuridine/DNA (BrdUrd/DNA) staining method in flow cytometry (FCM), we have developed a cell resistance index to Ara-C (RI). The technique has been applied to 121 bone marrow (BM) samples from patients with de novo AML treated by a regimen containing Ara-C and daunorubicin (DNR). Ninety-seven patients achieved a complete remission (CR), and 24 patients did not and were considered drug-resistant (DR). The BM cells collected at diagnosis were cultured for 48 hours and underwent BrdUrd/DNA analysis. Among 25 patients with no or very low proliferative activity (<3% of cells in S-phase), the proportion of DR patients (nine of 25) was significantly higher than in a second group of 96 patients with detectable proliferative activity (15 of 96) (P < .025). Within this second group, there was a first group of nine patients with high RI values, which included only DR patients; a second group of 63 patients with low RI values, which included 62 CR patients; and a third group of 24 patients with intermediate RI values, which included 19 CR and five DR patients. In view of this series, our results show that it is possible to detect a majority of DR patients treated by Ara-C.
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PMID:Detection of cytarabine resistance in patients with acute myelogenous leukemia using flow cytometry. 804 60

The hypothesis that use of personal electric appliances may be associated with increased risk of acute nonlymphocytic leukemia in adults was tested using interview data from a previously completed case-control study of 114 cases and 133 controls conducted between 1981 and 1984. Cases were obtained from a population-based cancer registry in western Washington state, and controls were obtained from the same area by random digit dialing. Of 32 electrical home appliances for which data on use were available for adult acute nonlymphocytic leukemia cases and controls, three motor-driven personal appliances (electric razors, hair dryers, and massage units) were selected a priori because their use represents exposure to higher peak magnetic fields than that from most other home appliances. When compared on an "ever used" versus "never used" basis, use of one or more of these appliances was not associated with increased risk of leukemia in the population studied (odds ratio (OR) = 0.71, 95% confidence interval (CI) 0.41-1.24). When the appliances were considered individually, massage units were more likely to have been used by cases than by controls (OR = 3.00, 95% CI 1.43-6.32), while hair dryers were more likely to have been used by controls than cases (OR = 0.38, 95% CI 0.22-0.66). There was a nonsignificant tendency for electric razor use to differentiate the cases from controls (OR = 1.33, 95% CI 0.80-2.23). When reported daily time of use was stratified, there was no overall increased risk with increased time of use except for electric razors (p < 0.05). In addition to the analysis of appliance use data from the case-control study, the authors obtained several models of these motor-driven personal appliances and characterized the magnetic fields they produce. Magnetic field flux density, or the B-field, and spectral measurements showed that partial body exposure from such appliances may exceed 0.5 mTesla (root mean squared) at rates-of-change exceeding 10 Tesla/sec. These epidemiologic data must be interpreted cautiously because the number of cases is limited and because of proxy reporting of appliance use for deceased cases. Nevertheless, the authors believe these data indicate that peak magnetic field exposure from personal appliances warrants further investigation as a possible risk factor for acute nonlymphocytic leukemia in adults.
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PMID:Adult leukemia risk and personal appliance use: a preliminary study. 865 Dec 38

The success of fludarabine as a single agent for therapy of chronic lymphocytic leukemia suggested its use in other leukemias such as adult acute myelogenous leukemia. Because doses that are tolerated in the clinic were not effective in the treatment of acute myelogenous leukemia, our approach was to combine low dose fludarabine with other active agents such as arabinosylcytosine (ara-C). This is also based on the rationale that fludarabine pretreatment modulates the metabolism of ara-C resulting in potentiation of the accumulation of its triphosphate. Improved response rates and clinical efficacy of this combination further suggested combining this couplet with DNA damaging agents, because the active triphosphates of both these analogs inhibit replication and repair processes of DNA synthesis.
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PMID:Fludarabine for treatment of adult acute myelogenous leukemia. 812 34


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