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)

We studied the iron status of 32 evaluable adult acute myeloid leukaemia (AML) survivors who were entered into the UK Medical Research Council acute myeloid leukaemia (AML) 10 and 12 trials at our institution between 1988 and 1998. Patients were required to have been independent of all blood products for at least 3 years. As a group, the median first serum ferritin level was 1323 mug/l (NR 19-300 mug/l) at a median of 1321 days from the last transfusion confirming the presence of significant iron overload persisting for some years after completion of all therapy and blood products. There was a general trend for the serum ferritin level to fall with time, but the fall was less pronounced in men and carriers of the C282Y mutation. Recipients of autologous stem cell transplantation (SCT) had a higher median first serum ferritin level (3245 mug/l) than patients who received chemotherapy alone (1148 mug/l) or allogeneic SCT (1334 mug/l) because of increased use of transfused blood. Nine of the 10 recipients of autologous SCT underwent venesection. No evidence of end organ damage was seen in any patient. Serial monitoring of serum ferritin and assessment of the C282Y status may be useful in all long-term AML survivors, especially autograft recipients.
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PMID:Autografting as a risk factor for persisting iron overload in long-term survivors of acute myeloid leukaemia. 1456 92

Transferrin receptor 1 (TfR1) is a type II membrane protein that mediates cellular iron uptake. Transferrin receptor 2(TfR2), another receptor for transferrin (Tf), has recently been cloned. We examined expression levels of TfR1, TfR2-alpha (membrane form) and TfR2-beta (non-membrane form) transcripts in cells from 67 patients with de novo acute myeloid leukaemia (AML) using reverse transcription-polymerase chain reaction (RT-PCR), and correlated the results with a variety of clinical features and disease outcomes of these patients. Significant correlations were noted between the levels of both TfR1 and TfR2-alpha (r = 0.771, P < 0.001) and TfR1 and TfR2-beta (r = 0.534, P < 0.001). Unexpectedly, initial white blood cell (WBC) counts were inversely correlated with levels of expression of either TfR1(r = -0.357, P = 0.003), TfR2-alpha (r = -0.486, P < 0.0001), or TfR2-beta (r = -0.435, P = 0.0003). Only TfR2 expression was significantly associated with either serum iron (r = -0.270, P = 0.045) or serum ferritin (r = -0.364, P = 0.008). Multivariate analyses using Cox's proportional hazard model showed that elevated TfR2-alpha, but not TfR1 or TfR2-beta mRNA levels significantly contributed to a better prognosis for AML patients. Furthermore, a group with high expression levels of both TfR2-alpha and TfR2-beta survived significantly longer than a group without high expression of both of them (P < 0.01 by log-rank). The present study suggests that (i) TfRs-independent iron uptake might have an important role in in vivo proliferation of AML cells; (ii) expression of TfR2 (especially the alpha form) is a novel prognostic factor for patients with AML.
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PMID:Elevated levels of transferrin receptor 2 mRNA, not transferrin receptor 1 mRNA, are associated with increased survival in acute myeloid leukaemia. 1501 67

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematological diseases deriving from a clonally expanded precursor bone marrow cell. MDS are characterized by ineffective hematopoiesis, peripheral cytopenias of various degrees and increased risk for transformation into acute myeloid leukemia. The incidence is highest in elderly people. Diagnosis is based on morphology, exclusion of reactive causes of dyshematopoiesis and cytogenetics/FISH. Allogeneic stem cell transplantation, the only curative therapy so far, is not feasible for most of the patients. Other therapeutic options include supportive therapy such as blood transfusions and antibiotics, hematopoietic growth factors (rHuEPO, G-CSF), immunomodulating agents and chemotherapy. It is important to install iron chelation therapy in cases with long term transfusion dependency.
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PMID:[Myelodysplastic syndromes--an overview for the practitioner]. 1501 94

Acute panmyelosis with myelofibrosis (APMF) is an ill-defined disorder that may either evolve as a clonal hematopoietic condition or as a sequel of toxic exposure to the bone marrow (BM). Therefore, controversy and discussion continues as to whether APMF may be considered as a hyperfibrotic (de novo) myelodysplastic syndrome (MDS), as acute myeloid leukemia (AML) or as a severe toxic myelopathy with accompanying myelofibrosis. In this context scant knowledge exists about BM findings, but especially evolution of this disorder according to sequential examinations. Clinically patients present with pancytopenia, a very few blasts in the peripheral blood and no or little splenomegaly. Initially BM histopathology is characterized by different degrees of reticulin-collagen fibrosis and wide ranges of cellularity with a prominent left-shifted and often macrocytic erythropoiesis associated with a reduction and maturation defects of the neutrophil series. Most conspicuous are abnormalities of the megakaryocytes including loose clustering, dislocation towards the endosteal border and appearance of atypical microforms with compact nuclei. Moreover, besides myelofibrosis in a number of patients the interstitial compartment displays a remarkable inflammatory reaction with lymphoid nodules, abundant iron-laden macrophages, perivascular plasmacytosis and increase in microvessels. Repeatedly performed BM biopsies reveal an accumulation of dispersed or clustered CD34+ and lysozyme-expressing blasts in keeping with the insidious transformation into acute leukemia. Prognosis is unfavorable with a median survival of less than 1 year. In conclusion, APMF has to be regarded as a condition that shows considerable overlappings with primary hyperfibrotic MDS, AML and toxic myelopathy (secondary MDS) with accompanying myelofibrosis and therefore can not be considered as a definite clinical entity.
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PMID:Acute panmyelosis with myelofibrosis. 1516 Sep 39

Controversy continues whether acute panmyelosis with myelofibrosis (APMF) exists as a well-defined clinicopathological entity. Following exclusion of overt acute myeloid leukemia (AML), especially the megakaryoblastic subtype, a retrospective study was performed on 46 patients with clinical and morphological features suggesting the diagnosis of APMF. All patients had a bone marrow (BM) biopsy performed at onset, and 13 had follow-up examinations. Enzyme histochemical and immunohistochemical techniques were applied and BM features evaluated by a semiquantitative scoring system. Clinical findings consisted of pancytopenia associated with a left-shifted differential count of the peripheral blood (less than 5% blasts) and no or minor splenomegaly. During follow-up (median survival 9 months) 35 patients developed severe BM insufficiency and 10 transformed into overt AML. Although myelofibrosis was a characteristic finding, other BM features proved to be heterogeneous. Cellularity was reduced in 13 and increased in 25 specimens. Most prominent was a left-shifted, often macrocytic erythropoiesis and a maturation defect of the neutrophil series. In 15 patients an increase (less than 20%) in CD34+ progenitors, immature myelomonocytic cells, and megakaryoblasts was noted. Abnormalities of megakaryocytes (atypical microforms, clustering, dysplasia) were regularly present. The stroma showed an inflammatory reaction (perivascular plasmacytosis, lymphoid nodules, many macrophages, iron deposits) in about 50% of the samples. Sequential BM biopsies revealed an accumulation of lysozyme-expressing myelomonocytic and CD34+ progenitor cells suggesting an increase in blasts. In conclusion, APMF may not be a distinct entity, but includes hyperfibrotic myelodysplastic syndromes (MDS) either primary or secondary, a rare form of initial AML with fibrosis, and even cases of toxic myelopathy.
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PMID:Acute panmyelosis with myelofibrosis: a clinicopathological study on 46 patients including histochemistry of bone marrow biopsies and follow-up. 1517 58

The hereditary hemochromatosis (HHC) gene, HFE on chromosome 6p21.3, encodes a protein involved in iron homeostasis. HFE mutations have low penetrance with a mild effect on serum iron levels. Animal, twin, and population studies have shown that carrier state for C282Y can increase iron levels. A proportion of heterozygotes show slightly elevated serum iron levels. Increased serum iron has been suggested to increase the risk for oxidative damage to DNA. Epidemiologic studies established a correlation between iron levels and cancer risk. Case-control studies have reported associations between HFE mutations C282Y/H63D and several cancers, some of which in interaction with the transferrin receptor gene TFRC or dietary iron intake. Increased cancer risk in C282Y carriers is likely due to higher iron levels in a multifactorial setting. In childhood acute lymphoblastic leukemia (ALL), there is an association of C282Y with a gender effect in two British populations. No association has been found in acute myeloblastic leukemia and Hodgkin disease in adults. The childhood leukemia association possibly results from elevated intracellular iron in lymphoid cells increasing the vulnerability to DNA damage at a critical time window during lymphoid cell development. Interactions of HFE with environmental and genetic factors, most of which are recognized, may play a role in modification of susceptibility to leukemia conferred by C282Y. Given the population frequency of C282Y and the connection between iron and cancer, clarification of the mechanism of HFE associations in leukemia and cancer will have strong implications in public health.
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PMID:HFE gene mutations in susceptibility to childhood leukemia: HuGE review. 1577 51

There are increasing evidences regarding the association between iron overload and extra-hepatic malignancies. We studied the prevalence of 12 hereditary hemochromatosis (HH) gene mutations (C282Y, V53M, V59M, H63D, H63H, S56C, Q127H, E168Q, E168X, W169X and Q283P in the HFE gene and Y250X in the TFR2 gene) and its correlation with the iron status in 82 adult patients with acute leukemia (AL); 48 patients (58.5%) were affected by acute myeloid leukemia (AML) and 34 patients (41.5%) by acute lymphoblastic leukemia (ALL); 27 patients (32.9%) had at least one HH gene mutation (6 heterozygous for C282Y, 6 homozygous for H63D, 13 heterozygous for H63D and 2 heterozygous for S56C). Mean serum ferritin levels at diagnosis were increased (822.5+/-811.4 microg/L). However, there was no difference between patients positive or negative for the HH gene mutations. Similarly, we did not observe any statistically significant difference as far as iron status between AML and ALL patients. Our study does not support the evidence of an association between hemochromatosis gene mutations and iron overload in AL patients.
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PMID:Analysis of HFE and TFR2 gene mutations in patients with acute leukemia. 1586 6

Need for iron increases rapidly during adolescence. In girls, this is primarily due to the beginning of menstruation and dieting to loose weight, while in boys increased erythropoetic activity during pubertal period is the major cause. Between November 1999 and June 2000, 2,900 patients, between 9-17 years of age were screened for the presence of anemia in our Adolescent Outpatient Clinic. Tanner's scale of sexual maturation was used to categorize genital development. Those patients diagnosed with anemia were further examined for bone age, history of pica, parasitosis and gastrointestinal symptoms. Complete blood count showed anemia in 44 patients. Twenty one patients (15 girls and 6 boys) were diagnosed with iron deficiency anemia, 19 (15 girls and 4 boys) were diagnosed with anemia associated with infections, 3 (two girls and one boy) were carriers for beta-thalasemia and one girl had acute myeloblastic leukemia. Laboratory parameters alone were not enough in the diagnosis of iron deficiency, but age, sex, growth rate and sexual maturation stage in the pubertal period must be taken into consideration. We suggest that the reason for the lower rate of iron deficiency anemia in our patients, than expected for this age group, could be due to our patient population being more aware and careful about a balanced diet compared to the feeding behaviour of the general population in Turkey. Further studies that include lower socio-economic groups are necessary to conclude the prevalance of iron deficiency anemia among adolescents.
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PMID:Iron deficiency anemia in a group of Turkish adolescents: frequency and contributing factors. 1597 30

Triapine, an iron chelator and a potent inhibitor of ribonucleotide reductase, has significant anti-leukemia activity. A phase I study of Triapine in combination with ara-C was conducted in 32 patients with refractory acute leukemia and high-risk MDS. Triapine (105 mg/m2/day 6-h infusion) was followed immediately by ara-C [100 (n=4), 200 (n=6), 400 (n=7), or 800 (n=8)mg/m2/day] as an 18-h infusion for 5 consecutive days. Dose-limiting toxicities (DLTs) were observed at the 800 mg/m2 ara-C dose level (one patient each with grade 4 mucositis; grade 4 neutropenic colitis, sepsis; grade 4 neuropathy; and grade 4 hyperbilirubinemia). Therefore, the study was amended to include an ara-C dose level of 600 mg/m2/day, no DLTs occurred in seven patients treated at this dose level. Mean Triapine C(max) and AUC were 1.13 microg/mL and 251.5 minmicrog/mL. Of 31 evaluable patients, 4 (13%) (3 AML, 1 Ph+ALL) achieved a CR (1 at a dose of 800 mg/m2; 2 at 600 mg/m2; 1 at 200mg/m2). The recommended phase II regimen is Triapine 105 mg/m2/day followed by ara-C 600 mg/m2/day for 5 consecutive days every 3-6 weeks.
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PMID:Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. 1647 31

We report 2 cases of ground-glass hepatocyte inclusions occurring in pediatric patients. Case 1 had alpha-thalassaemia major and was receiving iron chelation therapy, whereas case 2 had trisomy 21 with a history of bone marrow transplantation for acute myeloid leukemia. The liver sections in both cases showed eosinophilic, periodic acid-Schiff diastase-positive intracytoplasmic inclusions that were negative for hepatitis B surface antigen. Immunohistochemically the inclusions showed positive staining with KM279, a monoclonal antibody against polyglucosan derived from Lafora inclusions. On electron microscopy, in case 1, intracytoplasmic inclusions were composed of degenerate organelles, glycogen, and irregular fibrillar structures; in case 2, they were composed of vesicular structures containing granular material. Ultrastructural changes in both cases differed from classical Lafora inclusions and ruled out hepatitis B surface antigen, glycogenosis type IV, and fibrinogen storage disease. Genetic analysis of the Lafora's disease genes performed in case 2 revealed no mutations. The development of hepatocyte cytoplasmic inclusions in both our cases could be related to medication effects, because similar inclusions were reported in patients using cyanamide. Drug-induced inclusions, mimicking Lafora's disease, should be included in the differential diagnosis of hepatocyte ground-glass inclusions.
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PMID:Lafora-like ground-glass inclusions in hepatocytes of pediatric patients: a report of two cases. 1792 93


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