PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Acute myeloid leukemia”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1996

Cell differentiation in acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by a differentiation block leading to accumulation of immature cells. Chromosomal translocations in AML affect transcription factors that are involved in regulation of myeloid differentiation. Aberrant expression of these factors interferes with differentiation events and has a role in the pathogenesis of AML through superactivation or (dominant negative) repression of genes regulating proliferation and differentiation or by interference with assembly of the transcription complex for these genes. The maturation arrest can be reversed by certain agents as judged by results from investigations of myeloid leukemic cell lines and from treatment of acute promyelocytic leukemia (APL) patients with all-trans retinoic acid. Inactivation of the p53 and retinoblastoma (Rb) tumor suppressor genes is also associated with the pathogenesis of leukemia through effects on the cell cycle, and manipulation of these genes can affect differentiation of AML cells. With differentiation therapy, when successful as in APL, the leukemic cell mass is reduced to allow restoration of normal hematopoiesis and clinical remission, but the disease is not cured. However, initial reduction of the cell mass by maturation can increase the probability for cure with chemotherapy. Overexpression of suppressor genes may increase the probability for differentiation. Most probably, particular molecular defects of subgroups of AML have to be explored to find optimal strategies for treatment including both blocking the cell cycle, promoting terminal differentiation, and inducing apoptosis as well as strengthening the immune response.

Cell Cycle↗
PubMed1981

Spontaneous "remission' of agnogenic myeloid metaplasia and termination in acute myeloid leukemia.

Acute myeloid leukemia developed in two men with well-documented agnogenic myeloid metaplasia 49 and 27 months, respectively, after initial diagnosis. Both men had spontaneous hematologic remissions of myeloid metaplasia 22 and 16 months prior to leukemic transformation. Neither patient received any precedent radiation or cytotoxic chemotherapy. The remissions and subsequent transformation to acute leukemia were documented by bone marrow aspiration, biopsy, and reticuloendothelial marrow scans, as well as in vitro cell cultures and cytogenetic study. A review of the literature revealed nine other patients who had conversion to acute leukemia in the absence of preceding radiation or cytotoxic chemotherapy. However, the hematologic remission prior to transformation to leukemia.

Bone Marrow↗
PubMed2004

Expression of the neural cell adhesion molecule CD56 is not associated with P-glycoprotein overexpression in core-binding factor acute myeloid leukemia.

Acute myeloid leukemia (AML) with rearrangement of the core-binding factor (CBF) alpha or beta subunit gene has a favorable prognosis, but CD56 expression in CBFalpha-AML is associated with short disease-free survival. A proposed mechanism is overexpression of the multidrug resistance (MDR) protein P-glycoprotein (Pgp). CD56 expression, Pgp expression and function, and expression of the additional MDR proteins multidrug resistance protein-1 (MRP-1), lung resistance protein (LRP) and breast cancer resistance protein (BCRP) were studied in pretreatment blasts from 25 CBF-AML patients. CD56 expression was frequent in CBFalpha but rare in CBFbeta, and Pgp expression and function were frequent in both subtypes. CD56 expression did not correlate with Pgp expression or function, nor with expression of the other MDR proteins. Treatment failure associated with CD56 expression in CBFalpha-AML is not likely attributable to Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Managing therapy in older adult patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is predominantly a disease of older adults, with more than 50% of cases occurring in adults over 60 years of age. Treatment of AML in older adults is complicated not only by comorbidities that are common in this patient population, but also by the prevalence, in this age group, of forms of AML with a poor prognosis. The problems encountered and the strategies that have been used to improve the outlook in older adults with AML are presented. The two main strategies for improving outcomes in older adults with AML are to develop effective chemotherapeutic regimens with improved tolerability, and to reduce drug resistance. In studies to identify optimal chemotherapeutic regimens in older adults, a satisfactory balance between efficacy and toxicity has not yet been achieved. Also, the use of growth factors to promote hematopoietic recovery has yet to yield consistent reductions in treatment-related morbidity or mortality. Drug resistance can be modified by inhibiting drug efflux mechanisms or by increasing sensitivity to cytotoxic agents, but these strategies have not yet been shown to significantly affect outcomes. Novel approaches including antibody-targeted and molecular-targeted chemotherapy may have the potential to improve the prognosis for older adults with AML.

Adolescent↗
PubMed2003

DNA microarray analysis of hematopoietic stem cell-like fractions from individuals with the M2 subtype of acute myeloid leukemia.

Acute myeloid leukemia (AML) may develop de novo or secondarily to myelodysplastic syndrome (MDS). Although the clinical outcome of MDS-related AML is worse than that of de novo AML, it is not easy to differentiate between these two clinical courses without a record of prior MDS. Large-scale profiling of gene expression by DNA microarray analysis is a promising approach with which to identify molecular markers specific to de novo or MDS-related AML. This approach has now been adopted with AC133-positive hematopoietic stem cell-like fractions purified from 10 individuals, each with either de novo or MDS-related AML of the M2 subtype. Sets of genes whose activity was associated with either disease course were identified. Furthermore, on the basis of the expression profiles of these genes, it was possible to predict correctly the clinical diagnosis for 17 (85%) of the 20 cases in a cross-validation trial. Similarly, different sets of genes were identified whose expression level was associated with clinical outcome after induction chemotherapy. These data suggest that, at least in terms of gene expression profiles, de novo AML and MDS-related AML are distinct clinical entities.

Antigens, CD↗
PubMed2006

Leukocyte count as a predictor of death during remission induction in acute myeloid leukemia.

Acute myeloid leukemia (AML) presenting with a high leukocyte count has been associated with an increase in induction mortality and poor results in a number of other survival measures. However, the level at which an elevated leukocyte count has prognostic significance in AML remains unclear. In this report on a series of 375 adult (non-M3) AML patients undergoing induction chemotherapy at a single institution, leukocyte count analyzed as a continuous variable is shown to be a better predictor of induction death (ID) and overall survival (OS) than a leukocyte count of > or = 100 x 10(9)/L, a value characteristically associated with "hyperleukocytosis" (HL). In this patient cohort, a presenting leukocyte count of > or = 30 x 10(9)/L had high sensitivity and specificity for predicting ID, and both performance status (PS) and leukocyte count more accurately predicted for ID than age. Considering these parameters in newly-diagnosed AML patients may facilitate the development of strategies for reducing induction mortality.

Adolescent↗
PubMed2006

FLT3 internal tandem duplication in CD34+/CD33- precursors predicts poor outcome in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a clonal disease characterized by heterogeneous involvement of hematopoietic stem cell/progenitor cell populations. Using FLT3 internal tandem duplication (FLT3/ITD) as a molecular marker, we tested the hypothesis that clinical outcome in AML correlates with disease involvement of CD34(+)/CD33(-) precursors. Diagnostic specimens from 24 children with FLT3/ITD-positive AML were sorted by fluorescence-activated cell sorting (FACS), and resultant CD34(+)/CD33(-) and CD34(+)/CD33(+) progenitors were analyzed directly and after colony-forming cell (CFC) assay for the presence of FLT3/ITD. FLT3/ITD was present in all CD34(+)/CD33(+) patient samples. In contrast, FLT3/ITD was detected in CD34(+)/CD33(-) progenitors in only 19 of 24 samples. A bipotent progenitor was affected in a subset of patients, as evidenced by the presence of FLT3/ITD in both granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) colonies. Those patients in whom CD34(+)/CD33(-) precursors harbored the FLT3/ITD had worse clinical outcome; actuarial event-free survival (EFS) at 4 years from study entry for those patients with and without FLT3/ITD detection in CD34(+)/CD33(-) progenitors was 11% +/- 14% versus 100% +/- 0%, respectively (P = .002). This study suggests that FLT3/ITD involvement in CD34(+)/CD33(-) precursors is heterogeneous and that detection of the mutation in the less-mature progenitor population may be associated with disease resistance.

Alleles↗
PubMed2005

Bone marrow hyaluronan distribution in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a clonal disorder characterized by abnormal proliferation of myeloid cell precursors. Research has mainly focused on the cellular events, but the bone marrow matrix has attracted minor interest. In this study bone marrow biopsies were obtained from 35 newly diagnosed AML patients. The bone marrows were analyzed regarding the occurrence and distribution of hyaluronan (HYA) and reticulin fibers (type III collagen). The bone marrow sections were analyzed histochemically and compared with bone marrows from 30 healthy controls. The HYA staining was significantly stronger in the AML patients compared with the controls. Only one patient demonstrated abnormal reticulin staining score, but in the group of patients with antecedent myelodysplastic syndrome (MDS), the reticulin staining score was significantly higher compared with the patients with de novo AML. There was a significant correlation between the HYA staining and reticulin staining scores in the AML patients as was seen in the control group.

Adult↗
PubMed2006

Perspectives of proteomics in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a frequent hematological malignancy. Despite enormous therapeutic efforts that range from various cytotoxic agents to allogeneic stem cell transplantation, overall survival of patients with AML remains unsatisfying. The poor survival rates are mainly due to therapy-related mortality, failure of induction chemotherapy and early relapses. Therefore, novel therapeutic agents that are more efficient and better tolerated are eagerly sought after. For existing therapeutic strategies, there is a lack of markers that are capable of reliably predicting prognosis or the therapeutic response prior to treatment. There is hope that elucidation of the AML-specific proteome will prompt the discovery of novel therapeutic targets and biomarkers in AML. Modern mass-spectrometry instrumentation has achieved excellent performance in terms of sensitivity, resolution and mass accuracy; however, so far, the contribution of proteomics to the care of patients with AML is virtually zero. This might be partly because mass spectrometry instrumentation and protein fractionation still lack true high-throughput capabilities with highest levels of reproducibility, thus hampering large-scale translational studies with clinical samples. Since mass-spectrometry instruments are very intricate devices, their successful operation will hinge on the willingness and ability of mass-spectrometry experts and clinical researchers to adopt new views, learn from each other and cooperate in order to ultimately benefit the patient suffering from AML. This review highlights some clinical problems circumventing the treatment of patients with AML. Furthermore, it provides a brief overview of the technical background of standard proteomics approaches and describes opportunities, challenges and pitfalls of proteomic studies with regards to AML.

Biomarkers, Tumor↗
PubMedDate not supplied

Mylotarg approved for patients with CD33+ acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common adult leukemia and has historically been treated with intensive multiagent chemotherapy. In May 2000, the U.S. Food and Drug Administration approved a new agent, gemtuzumab ozogamicin (Mylotarg) to treat patients who are 60 years and older in first relapse with CD33+ AML and not considered candidates for chemotherapy. Gemtuzumab is an antibody-targeted agent that binds specifically to the CD33 antigen that is found on the surface of more than 80% of patients with AML. The agent is administered via i.v. over two hours, and premedication with acetaminophen and diphenhydramine is recommended. Side effects include fever, chills, neutropenia and thrombocytopenia, and asymptomatic hypotension. Clinical remissions have been observed with gemtuzumab, and additional trials with this new agent currently are being conducted.

Aminoglycosides↗
PubMed1991

Dysmegakaryopoiesis resembling acute megakaryoblastic leukemia in treated acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by trilineage dysplasia, including atypical megakaryocytes. Acute megakaryoblastic leukemia (FAB M7) is particularly associated with atypical megakaryocytic hyperplasia (AMH). Fifteen patients with nonmegakaryoblastic AML developed AMH after therapy, comprising 12.6% of cases of AML diagnosed from 1986 to 1989. Platelet counts were normal in nine patients and decreased in six. Blasts comprised less than 5% of cells in 40% of the biopsies, ranged from 5-15% in 53%, and comprised more than 30% of cells in 7%. Numerous small hypo- and hyperlobated megakaryocytes were seen in all specimens, often occurring in clusters, and were more easily seen in sections than in smears. Subsequent biopsies in 13 patients showed a remission marrow in seven, increased blasts in three, and AML in three; none showed AMH. AMH resembling acute megakaryoblastic leukemia may be seen transiently after treatment of AML.

Acute Disease↗
PubMed1983

Use of monoclonal antibodies as a diagnostic tool in human leukemia. I. Acute myeloid leukemia and acute phase of chronic myeloid leukemia.

Various monoclonal antibodies (mAbs) detecting certain different epitopes on myeloid cells (VIMD5, D5 D6, OKM1, Leu-M3, VIEG4, OKIa 1) have been used in combination with conventional markers (antihuman myeloid hetero-antiserum, FcIgG-receptors, C3d-receptors) to further define the phenotypic heterogeneity of myeloid leukemia. Subsequent leukemic samples from previously untreated patients with acute myeloid leukemia (AML) (51 adults, 24 children) and from nine adult patients in the acute phase of chronic myeloid leukemia (CML-BC) were studied. It was possible to demonstrate quantitative differences in the expression of antigens on the various leukemia subtypes which could be exploited for diagnosis. Furthermore our results revealed that there is a very close correlation between the different surface phenotypes and the types morphologically assessed according to FAB-criteria.

Adult↗
PubMed1990

Significance of lineage specific differentiation markers for complex classification of acute leukemias. I. Acute myeloid leukemias.

Acute leukemias are clonal malignant neoplastic diseases which do not originate from the transformation of totipotent hematopoietic stem cells but of progenitors committed to the myeloid, T-lymphatic or B-lymphatic differentiation lineage. The transforming event seems to be associated with a nonrandom aberrant DNA rearrangement. Although a leukemic population is clonal, originating from a single cell, it exhibits phenotypic, and sometimes even karyotypic, heterogeneity. Leukemic cells are allocated to a particular differentiation cell lineage on the basis of a positive finding of the lineage specific differentiation marker (LSDM) in the presented classification of acute leukemias. Criteria for common types of acute myeloid leukemias are described and the possible existence of several other types is discussed.

Cell Differentiation↗
PubMed2003

Epidemiology and clinical burden of acute myeloid leukemia.

Acute myeloid leukemia is the most common type of leukemia in adults, yet it continues to have the lowest survival rate of all leukemias. Prognosis for the elderly in particular continues to be dismal. This review examines the currently available literature on the epidemiology, etiology, diagnosis and management of acute myeloid leukemia. New therapies and therapeutic strategies must be found to improve survival, especially as the worldwide population ages. Gemtuzumab ozogamicin (Mylotarg) for the treatment of patients with CD33-positive acute myeloid leukemia, selective FLT3 inhibitors currently in advanced development (e.g., SU11248, PKC412, CT53518 and CEP-710) and other targeted compounds (e.g., farnesyl transferase inhibitors, BCL-2 inhibitors and interleukin-2) may present initial opportunities to achieve improved outcomes.

Age Factors↗
PubMed1989

Concomitant chronic lymphocytic leukemia, acute myeloid leukemia, and thrombosis with protein C deficiency. Case report and review of the literature.

A patient is reported who presented simultaneously with two distinct forms of leukemia: chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). The diagnosis of CLL was supported by the presence of lymphocytosis, lymphadenopathy, and splenomegaly with mature B-cell markers on the population of lymphoid cells in the bone marrow. AML was documented by the presence of circulating blast cells and 50% blasts with myeloid markers and Auer rods in the bone marrow. A complete remission from both forms of leukemia was obtained after treatment for the AML. The patient also experienced the temporal occurrence of venous thrombosis for the first time at the age of 69 years, shortly before the diagnosis of leukemia. Protein C deficiency was documented and may have been hereditary as suggested by the strong family history of thrombosis or alternatively may have been the consequence of one of the leukemias.

Aged↗
PubMed2004

Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia.

Acute myeloid leukemia subtype M4 with eosinophilia is associated with a chromosome 16 inversion that creates a fusion gene CBFB-MYH11. We have previously shown that CBFB-MYH11 is necessary but not sufficient for leukemogenesis. Here, we report the identification of genes that specifically cooperate with CBFB-MYH11 in leukemogenesis. Neonatal injection of Cbfb-MYH11 knock-in chimeric mice with retrovirus 4070A led to the development of acute myeloid leukemia in 2-5 months. Each leukemia sample contained one or a few viral insertions, suggesting that alteration of one gene could be sufficient to synergize with Cbfb-MYH11. The chromosomal position of 67 independent retroviral insertion sites (RISs) was determined, and 90% of the RISs mapped within 10 kb of a flanking gene. In total, 54 candidate genes were identified; six of them were common insertion sites (CISs). CIS genes included members of a zinc finger transcription factors family, Plag1 and Plagl2, with eight and two independent insertions, respectively. CIS genes also included Runx2, Myb, H2T24, and D6Mm5e. Comparison of the remaining 48 genes with single insertion sites with known leukemia-associated RISs indicated that 18 coincide with known RISs. To our knowledge, this retroviral genetic screen is the first to identify genes that cooperate with a fusion gene important for human myeloid leukemia.

Acute Disease↗
PubMed2002

Detection of minimal residual disease in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a curable malignancy, but its cure rate remains disappointingly low. Accurate quantitation of residual AML cells would allow individualization of therapy and thereby increase the likelihood of cure for each patient. Techniques that are being studied for residual disease detection include molecular assays for abnormalities that are present in subsets of AML patients, and multiparameter flow cytometry, which has broader applicability. Although significant advances have been made in the development of assays for monitoring residual disease, and particularly in techniques for molecular quantitation, additional refinement and validation are needed before these assays can be applied routinely in clinical management.

Acute Disease↗