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)

Clinical trials of colony-stimulating factors (CSFs) have been conducted for over 10 years. Initially, these agents, generally either granulocyte-macrophage (GM)- or granulocyte (G)-CSF, were hypothesized to reduce rates of major infection and/or death in the initial weeks after administration of chemotherapy. Although trials have consistently shown that both cytokines accelerate neutrophil recovery, only 1 out of 5-10 large randomized trials has reported that a decrease in major infection occurs as a result. While some of these trials have found that the use of cytokines lowers days in hospital, on antibiotics, or with fever, it is unclear whether the magnitude of these effects outweighs the expense currently entailed in CSF administration; indeed it appears that estimates of cost are themselves quite variable. The second major use of cytokines has been in priming acute myeloid leukaemia (AML) blasts to the cytotoxic actions of chemotherapy. Here again, the results of several randomized trials do not justify application of this strategy. It remains possible that there are subsets of AML patients who would benefit from priming. However, the identification of such patients might require years of accrual into clinical trials from which the majority of patients would not benefit. Future years may see trials of cytokines (e.g. pegylated recombinant human megakaryocytic growth and development factor +G- or GM-CSF) in patients in remission and as a means to increase the number of normal granulocytes that can be given to patients with infections. Further therapies may target cytokine receptors on AML blasts, to improve anti-leukaemia therapy.
Best Pract Res Clin Haematol 2001 Mar
PMID:Growth factors in acute myeloid leukaemia. 1135 30

The development of refractory disease in acute myeloid leukaemia (AML) is frequently associated with the expression of one or several multidrug resistance (MDR) genes. MDR1, MRP1 and LRP have been identified as important adverse prognostic factors in AML. Recently it has become possible to reverse clinical multidrug resistance by blocking P-glycoprotein-mediated drug efflux. The potential relevance of MDR and new approaches to treat refractory disease, are discussed.
Best Pract Res Clin Haematol 2001 Mar
PMID:Chemotherapy resistance in acute myeloid leukaemia. 1135 32

We measured the bone mineral density in 22 patients with the cylindrical stemmed cobalt-chrome AML prosthesis (collared) and in 22 patients with the tapered stem titanium CLS prosthesis (collarless). DEXA scanning was undertaken at a mean of 40 months in the AML and 52 months in the CLS group from the time of implant insertion. In both groups the greatest mean loss of BMD was found in Gruen zone 7 and the least change in Gruen zone 5. In all zones the BMD loss was greater in the AML group but only statistically significant in zones 6 (P<0.05) and 7 (P<0.01). Although numerous factors affect BMD changes around cementless implants, this study suggests that less bone loss can be associated with the titanium CLS stem.
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PMID:Periprosthetic bone mineral density changes with femoral components of differing design philosophy. 1140 59

The myelodysplastic syndromes are a collection of five clinico-pathological entities with a wide spectrum of clinical behaviours and survival outcomes. Cytogenetic analysis has been instrumental in refining the prognosis, predicting the likelihood of progression to acute myeloid leukaemia and median survival, and in establishing clonality of these diseases. This review highlights the most frequent abnormalities and summarizes their clinical and genetic features.
Best Pract Res Clin Haematol 2001 Sep
PMID:The cytogenetics of myelodysplastic syndromes. 1164 Aug 66

During the last three decades it has become apparent that the majority of cases of acute myeloid leukaemia (AML) are characterized by at least one of a variety of recurrent chromosomal abnormalities. These changes have been found in many instances to correlate closely with distinct morphological features and clinical characteristics, the molecular basis of which is becoming increasingly understood. Furthermore, diagnostic karyotype has been shown to be a key determinant of outcome in AML, with mounting evidence to support the notion that cytogenetic analysis can serve to identify biologically distinct subsets of disease that demand tailored therapeutic approaches. This has led to a rising trend towards routine cytogenetic and molecular characterization of newly diagnosed acute leukaemia, providing a framework for treatment stratification.
Best Pract Res Clin Haematol 2001 Sep
PMID:The clinical significance of cytogenetic abnormalities in acute myeloid leukaemia. 1164 Aug 67

Childhood myeloid leukaemias are a diverse collection of conditions. Although many are also seen in adults, some are peculiar to childhood. In childhood AML, as in adults, cytogenetic abnormalities are associated with specific clinical features and define prognostic groups. In infants under 1 year with AML, the incidence of 11q23 abnormalities is particularly high. The finding of identical 11q23 breakpoints in infant leukaemia as in therapy-related leukaemias suggests a role for in utero exposure to topoisomerase II inhibitors. There are a number of constitutional disorders that predispose children to develop AML, usually with a preceding myelodysplastic phase. Monosomy (or deletion of the long arm) of chromosome 7 is the most frequent chromosome abnormality in the bone marrow of such patients. Abnormalities of chromosome 7 are also common cytogenetic findings in all morphological subgroups of childhood myelodysplasia, either as a primary abnormality or associated with disease progression.
Best Pract Res Clin Haematol 2001 Sep
PMID:Childhood myeloid leukaemias. 1164 Aug 70

This study assesses whether the kinetic response of AML cells to HGFs might help to predict initial clinical outcome of treatment in de novo AML in association with age, FAB type and karyotype. Best subset regression analysis indicated optimal variables to develop models to predict prognosis. High S-phase in surviving cells following 7 days incubation in SFM, resistance to stimulation by G+GM-CSF and poor karyotype taken in combination correctly predicted outcome in 83% of patients. The importance of high SFM S-phase may be to indicate autonomous proliferation therefore a leukemic clone more likely to regenerate following therapy at the expense of normal haemopoiesis. Kinetic studies of AML cells may be a useful predictor of outcome in addition to other more established prognostic factors.
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PMID:A novel predictive model of outcome in de novo AML based on S-phase activity and proliferative response of blast cells to haemopoietic growth factors. 1183 76

Immunophenotypic analysis of leukaemic cells using multiparametric flow cytometry has proved to be an attractive approach for MRD investigation in acute lymphoblastic leukaemia (ALL); by contrast, information on acute myeloid leukaemia (AML) is still scanty. Here, we first review the methodological strategies for these studies. Triple or quadruple antigenic combinations, analysed by multiparametric flow cytometry, have shown that in 80% of AML patients it is possible to identify aberrant or uncommon phenotypic profiles on blast cells, thereby allowing their distinction from normal cells and their use as leukaemia-associated phenotypes (LAP). We also focus on technical aspects that are important in the definition of LAP. We then review pitfalls that could potentially affect results using this approach. Finally, we review available information concerning the clinical value of these studies. Although reported data in the literature are still scanty, several authors have shown that this technique could be used for the prognostic evaluation of AML patients, when immunophenotypic evaluation is applied after induction therapy.
Best Pract Res Clin Haematol 2002 Mar
PMID:Immunological evaluation of minimal residual disease (MRD) in acute myeloid leukaemia (AML). 1198 19

Relapse remains the main cause of treatment failure in acute myeloid leukaemia (AML). Studies to date suggest that monitoring of minimal residual disease (MRD) in AML is useful in identifying patients at high risk of relapse from those in durable remission. This chapter describes the methodological advances in the detection of MRD and, in particular, focuses on the development of highly sensitive RT-PCR techniques, including real-time, for quantifying MRD. Preliminary results on the clinical utility of MRD monitoring in AML with t(8;21) and inv(16) are promising and provide the basis for further evaluation by quantitative real-time analysis in prospective clinical trials. For AML without a specific fusion transcript, the WT1 gene is an alternative molecular target. The clinical value of quantitative MRD monitoring in AML, however, will need to be confirmed in future studies.
Best Pract Res Clin Haematol 2002 Mar
PMID:Minimal residual disease in acute myeloid leukaemia. 1198 20

Acute promyelocytic leukaemia (APL) is characterized by the t(15;17)(q22;q21) leading to the formation of PML-RARalpha and RARalpha-PML fusion genes which provide suitable targets for the assessment of minimal residual disease (MRD). Studies have focused upon detection of PML-RARalpha because, although assays for RARalpha-PML transcripts are more sensitive, they are not applicable to 25% of cases. Among patients receiving standard therapy (ATRA and anthracycline-based chemotherapy), qualitative assays using a nested reverse transcriptase-polymerase chain reaction (RT-PCR), which typically achieve sensitivities of 1 in 10(4), have been found to provide independent prognostic information suitable for directing an approach to treatment. Detection of PML-RARalpha at the end of consolidation, or subsequent recurrence of PCR positivity, heralds relapse, which may, however, be averted by additional therapy leading to improvements in survival for this "high-risk" subgroup of patients. MRD analysis has also proved of value in predicting response to autologous transplant procedures undertaken in second complete remission and in directing the need for additional therapy in the post-transplantation setting. Overall, these studies undertaken within the context of a relatively homogeneous disease entity confirm that MRD monitoring provides independent prognostic information, serving as a valuable model for improving treatment strategy in other molecularly defined subsets of acute myeloid leukaemia (AML). Nevertheless, conventional nested RT-PCR assays fail to detect residual disease in a significant proportion of patients who ultimately relapse, which may be a reflection of RNA quality and/or assay sensitivity. Therefore, it is hoped that "real-time" quantitative RT-PCR technology (RQ-PCR) which permits quantification of fusion gene transcripts in relation to endogenous control genes will be even more predictive of outcome and achieve greater standardization of MRD detection in the context of large-scale clinical trials.
Best Pract Res Clin Haematol 2002 Mar
PMID:The significance of minimal residual disease in patients with t(15;17). 1198 21


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