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)

The present study evaluated the serum levels of known angiogenic factors and analysed their prognostic significance in patients with acute or chronic leukemia. Enzyme-linked immunosorbent assays (ELISAs) were performed to quantify the basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), tumor necrosis factor-alpha (TNF-alpha), angiogenin, and matrix metalloproteinase-9 (MMP-9) in stored samples obtained before treatment from patients with acute myeloid leukemia (AML; 30 patients), acute lymphoblastic leukemia (ALL; 10 patients), and chronic myelogenous leukemia (CML; 14 patients). The levels of VEGF, HGF, angiogenin, and MMP-9 were all significantly higher in patients with CML than in healthy individuals. The HGF levels were also higher in patients with AML than in healthy individuals, plus there was a significant correlation between the HGF level and the white blood cell count, monocyte count, and serum level of lactate dehydrogenase (LDH) in patients with AML. In a univariate analysis, age and HGF level were both found to be significant parameters predictive for an achievement of complete remission (CR) in patients with AML. Meanwhile, in a multivariate analysis using a logistic regression model, the HGF level was the only parameter strongly predictive for CR (P=0.047). The leukemia-free survival (LFS) rate for AML patients with a lower HGF concentration was better than that for AML patients with a higher HGF concentration (1 year LFS rates=75.0% vs. 37.5%, P=0.065). The HGF concentration was an independent prognostic factor for an achievement of CR, plus higher HGF concentrations were associated with a lower survival in patients with AML.
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PMID:Clinical implications of angiogenic factors in patients with acute or chronic leukemia: hepatocyte growth factor levels have prognostic impact, especially in patients with acute myeloid leukemia. 1601 34

To assess the prognostic relevance of mutations in the NPM1 gene encoding a nucleocytoplasmic shuttle protein in younger adults with acute myeloid leukemia (AML) and normal cytogenetics, sequencing of NPM1 exon 12 was performed in diagnostic samples from 300 patients entered into 2 consecutive multicenter trials of the AML Study Group (AMLSG). Treatment included intensive double-induction therapy and consolidation therapy with high cumulative doses of high-dose cytarabine. NPM1 mutations were identified in 48% of the patients including 12 novel sequence variants, all leading to a frameshift in the C-terminus of the nucleophosmin 1 (NPM1) protein. Mutant NPM1 was associated with specific clinical, phenotypical, and genetic features. Statistical analysis revealed a significant interaction of NPM1 and FLT3 internal tandem duplications (ITDs). NPM1 mutations predicted for better response to induction therapy and for favorable overall survival (OS) only in the absence of FLT3 ITD. Multivariable analysis for OS revealed combined NPM1-mutated/FLT3 ITD-negative status, CEBPA mutation status, availability of a human leukocyte antigen (HLA)-compatible donor, secondary AML, and lactate dehydrogenase (LDH) as prognostic factors. In conclusion, NPM1 mutations in the absence of FLT3 ITD define a distinct molecular and prognostic subclass of young-adult AML patients with normal cytogenetics.
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PMID:Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. 1605 34

We retrospectively analysed the significance of FLT3 mutations in patients with acute myeloid leukemia (AML) having a normal karyotype, who were treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation (auto-PBSCT). In all, 34 patients with normal karyotype AML in first complete remission receiving high-dose chemotherapy and auto-PBSCT were analysed based on the presence or absence of FLT3/ITDs and FLT3/D835. They were 16 males and 18 females and with a median age of 41.5 years. FLT3/ITDs were detected in eight of 34 patients (23.5 %), and FLT3 D835 mutations in two of 34 patients (5.9%). White blood cell count (P=0.0087), serum concentration of lactate dehydrogenase (P=0.005), and percentages of peripheral blood (P=0.0131) and bone marrow (BM) blasts (P=0.0312) were significantly higher in patients showing the FLT3 mutations. Overall survival (OS) and disease-free survival (DFS) were similar between patients with or without FLT3 mutations (5 year DFS, 67.5 vs 68.55%, P=0.819; 5 year OS, 64.81 vs 78.88%, P=0.4457, by the log-rank test). FLT3 mutations demonstrate no further prognostic impact in patients with normal karyotype AML in first CR treated with high-dose chemotherapy and auto-PBSCT. Myeloablative chemotherapy supported by auto-PBSCT may overcome any poor prognostic implications of FLT3 mutations.
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PMID:FLT3 mutations in normal karyotype acute myeloid leukemia in first complete remission treated with autologous peripheral blood stem cell transplantation. 1618 77

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.
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PMID:Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS). 1619 87

Tumor lysis syndrome (TLS) is defined by metabolic derangements occurring in the setting of rapid tumor destruction. In acute myelogenous leukemia (AML), TLS frequency, risk stratification, monitoring, and management strategies are based largely on case series and data from other malignancies. A single-center, retrospective cohort study was conducted to estimate TLS incidence and identify TLS predictive factors in a patient population undergoing myeloid leukemia induction chemotherapy. This study included 194 patients, aged 18-86 years, with AML or advanced myelodysplastic syndrome undergoing primary myeloid leukemia induction chemotherapy. Nineteen patients (9.8%) developed TLS. In univariate analysis, elevated pre-chemotherapy values for uric acid (P < 0.0001), creatinine (P = 0.0025), lactate dehydrogenase (LDH) (P = 0.0001), white blood cell (P = 0.0058), gender (P = 0.0064) and chronic myelomonocytic leukemia history (P = 0.0292) were significant predictors. In multivariate analysis, LDH (P = 0.0042), uric acid (P < 0.0001) and gender (P = 0.0073) remained significant TLS predictors. A predictive model was then designed using a scoring system based on these factors. This analysis may lay the groundwork for the development of the first evidence-based guidelines for TLS monitoring and management in this patient population.
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PMID:A predictive model for the detection of tumor lysis syndrome during AML induction therapy. 1675 59

CXCR4 chemokine receptors retain hematopoietic progenitors and leukemia cells within the marrow microenvironment. We prospectively evaluated the prognostic implication of CXCR4 in 90 consecutive patients with acute myelogenous leukemia (AML) by flow cytometry. Patients were divided into groups with low (n=32), intermediate (n=26), or high (n=32) CXCR4 expression, as defined by CXCR4 mean fluorescence intensity ratio thresholds of less than 5, 5 to 10, or more than 10, respectively. We found that low CXCR4 expression on AML cells correlated with a better prognosis, resulting in a longer relapse-free and overall survival of 24.3+/-2.9 months for low CXCR4-expressing patients, compared with 17.4+/-3.4 months for intermediate and 12.8+/-2 months (mean+/-SEM) for patients with high expression. In univariate analyses, CXCR4 expression, cytogenetics, white blood cell count, and serum lactate dehydrogenase (LDH) predicted for shorter survival. Multivariate analysis revealed CXCR4 expression and unfavorable cytogenetics as independent prognostic factors. We conclude that CXCR4 expression in AML is an independent prognostic predictor for disease relapse and survival that can rapidly and easily be determined at disease presentation. These findings warrant further investigation into the role of CXCR4 in AML and suggest that CXCR4 should be incorporated into the risk assessment of AML patients.
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PMID:CXCR4 is a prognostic marker in acute myelogenous leukemia. 1688 90

In this study, we analysed the prognostic relevance of foetal liver tyrosine kinase 3 (FLT3) mutations in 73 patients with acute myeloid leukaemia (AML) with normal karyotype, who survived induction and consolidation and received autologous stem cell transplantation (ASCT) after successful mobilization of peripheral blood stem cell (PBSC). There were 44 males and 29 females with a median age of 54 years (range 20-77). Overall, 16 out of 73 autografted patients (22%) had FLT3 mutations. More in detail, FLT3/ITDs were detected in 10 out of 73 patients (14%), while FLT3 D835 mutations were detected in five cases (7%). One patient (1%) was found as having both abnormalities. White blood cell count (p=0.009), serum concentration of lactate dehydrogenase (p=0.01), and percentages of peripheral blood (p=0.002) and bone marrow blasts (p=0.03) were significantly higher in patients showing the FLT3 mutations. On the contrary, overall survival and disease-free survival were similar between patients with or without FLT3 mutations (p=0.73 and 0.78, respectively). In conclusion, our data suggest that myeloablative chemotherapy supported by auto-PBSCT may overcome the adverse prognostic implications of FLT3 mutations in AML. However, it is to consider that autografted patients are highly selected for best response to induction, consolidation and mobilization, as well as for minor non-haematologic toxicity.
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PMID:Myeloablative chemotherapy followed by autologous stem cell infusion may overcome the adverse prognostic impact of FLT3 (foetal liver tyrosine kinase 3) mutations in patients with acute myeloid leukaemia and normal karyotype. 1703 74

The phosphoinositide 3-kinase (PI3K/Akt) pathway is activated in acute myelogenous leukemia (AML) and is promising for targeted inhibition. Ninety-two patients with primary AML were analyzed for PI3K/Akt constitutive activation. Fifty percent of the patients presented with constitutive PI3K activation (PI3K (+)). No difference was observed between PI3K (+) and PI3K (-) groups concerning age, sex, white blood cell count, lactate dehydrogenase (LDH) level, bone marrow blast cells, French-American-British (FAB) classification, cytogenetics, RAS or nucleophosmin (NPM) mutations. Slightly more FLT3-ITD was detected in the PI3K (-) group (P = .048). The complete remission rate was similar between the 2 groups. With a median follow-up of 26 months, we observed for PI3K (+) and PI3K (-) patients, respectively, 56% and 33% overall survival (P = .001) and 72% and 41% relapse-free survival (P = .001). Constitutive PI3K/Akt activity is a favorable prognosis factor in AML, even after adjustment for FLT3-ITD, and may confer a particular sensitivity to chemotherapy. A better understanding of the downstream effectors of the PI3K/Akt pathway is needed before targeting in AML.
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PMID:Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients. 1742 58

Disseminated intravascular coagulation (DIC) is one of the important complications to develop in patients with acute myeloid leukemia (AML). While acute promyelocytic leukemia (APL) is a strong risk factor for DIC, other clinical features have not been fully defined. We retrospectively analyzed 161 consecutive adult patients with de novo non-APL AML. DIC was diagnosed in 52 patients (32%); 28 patients at diagnosis and 24 soon after the initiation of induction chemotherapy. Leukocyte counts, C-reactive protein, and lactate dehydrogenase were significantly higher in the DIC+ group. Negative expressions of CD13, CD19, CD34, and HLA-DR were more prevalent in the DIC+ group. On multivariate logistic-regression analysis, variables that were independently associated with the development of DIC were high C-reactive protein, high leukocyte count, negative expressions of CD13 and HLA-DR, and cytogenetics with a normal karyotype or 11q23 abnormality. Although DIC is considered to be associated with serious morbidity and occasional mortality, we did not find any significant differences in the complete remission rate, overall or disease-free survival between DIC+ and DIC- groups. This study is the first to define the clinical characteristics associated with DIC in patients with non-APL AML, but exactly how and when DIC should be treated remains to be determined.
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PMID:Prevalence and clinical characteristics of acute myeloid leukemia associated with disseminated intravascular coagulation. 1787 27

From November 1, 1995 to July 31, 2004, 49 children with de novo acute myeloid leukemia (AML) were treated at our institution. One patient who was treated by a different protocol was excluded. In total, 48 patients with de novo AML were enrolled in this study. Forty-two patients with AML other than acute promyelocytic leukemia (non-APL) were treated consecutively with 2 novel protocols: Mackay Memorial Hospital (MMH)-AML-96, designed as a pilot phase, and Taiwan Pediatric Oncology Group (TPOG)-AML-97A, on the basis of MMH-AML-96 with minor modifications. Six patients with APL were treated consecutively with 2 protocols, TPOG-APL-97 and APL-2001. As of July 31, 2006, the remission rates were 79%, 92%, and 98% after 1, 2, and 3 courses of induction therapy, respectively. The 5-year overall survival was 64%+/-6.9% (SE), and the 5-year event-free survival was 60%+/-7.1%; for non-APL AML, the rates were 62%+/-7.5% and 59%+/-7.6%; for APL, 83+/-15.2 and 67+/-19.3%. Among the factors analyzed, a complete remission achieved after 1 course of induction therapy, lactate dehydrogenase <500 IU/L at diagnosis, patients without invasive fungal infection during chemotherapy, and male sex were associated with a favorable outcome.
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PMID:The development of a novel protocol for the treatment of de novo childhood acute myeloid leukemia in a single institution in Taiwan. 1809 Sep 30


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