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 developed a sensitive method of measurement of granulocyte colony-stimulating factor (G-CSF) by an enzyme-linked immunosorbent assay, which we applied in the plasma of the bone marrow aspirate in 70 patients with various hematological disorders. The lowest limit of detection by this method is 2 pg/ml. G-CSF was detected in all but two of the patients. Compared to the G-CSF level in normal healthy controls, those in non-Hodgkin's malignant lymphoma, aplastic anemia, agranulocytosis and multiple myeloma were significantly higher, while the level in refractory anemia was not different. The G-CSF level in acute myelogenous leukemia patients was either elevated or decreased regardless of the French-American-British subgroup. The level in acute lymphoblastic leukemia was not different from the normal value, as was that in refractory anemia with an excess of blasts, and that in chronic lymphocytic leukemia. A patient with chronic myelomonocytic leukemia showed initial elevation of G-CSF with normalization after entering complete remission. The G-CSF level in chronic myelogenous leukemia was significantly decreased, although one patient in hematological remission who was under alpha-interferon therapy showed normal levels. The level in polycythemia vera was not significantly different from the normal value. The G-CSF level for the entire group showed an inverse, although not statistically significant, correlation with the percentages of myeloid cells of the bone marrow (r = -0.174, p = 0.1703, n = 80). These results are thought to reflect the regulatory mechanism of granulopoiesis in the bone marrow in various hematological disorders, and it is concluded that this method may be of clinical use in the treatment of patients with these disorders and in the selection of candidates likely to benefit from G-CSF administration.
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PMID:The levels of granulocyte colony-stimulating factor in the plasma of the bone marrow aspirate in various hematological disorders. 872 2

A retrospective analysis was done on 113 patients (median age 73 years) with myelodysplastic syndromes (MDS), consecutively diagnosed at our center during a 10-year period. Patients with refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) had significantly longer survival than patients with refractory anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (CMML) or refractory anemia with excess blasts in transformation (RAEB-T). Thirty-seven patients (33%) subsequently developed acute myelogenous leukemia (AML). The percentages of AML transformation for the subgroups were: RA: 26%, RARS: 14%, RAEB: 38%, CMML: 25% and RAEB-T: 69%. A total of 9 patients received high-dose chemotherapy, 7 of them already at the time of MDS diagnosis. Six of the RAEB-T patients entered complete and two partial remission. The median age in the group of RAEB-T patients was significantly lower (62 years) than in the other MDS subgroups. It seems that high-dose chemotherapy, at least in RAEB-T, may induce complete remission and improve survival time.
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PMID:Myelodysplastic syndromes--a population-based study on transformation and survival. 760 54

The t(8;21) is a frequent chromosome abnormality in acute myeloid leukemia (AML), particularly associated with M2 of the French-American-British (FAB) classification, but also found in a few patients with myelodysplastic syndrome (MDS). The two genes involved in the t(8;21) have been recently isolated and the cDNA of the AML1/ETO fusion gene identified. We have investigated a series of AML and MDS patients by a reverse transcriptase-polymerase chain reaction (RT-PCR) and analyzed the clinical and laboratory features of leukemia with t(8;21). The t(8;21) was only found in a subset of M2, which had the clinical and hematological features distinct from those M2 without t(8;21). M2 with t(8;21) was associated with a significantly higher myeloid differentiation and with a good response to chemotherapy. Moreover, among the patients with refractory anemia with excess of blasts in transformation (RAEB-T) the t(8;21) was also significantly associated with a higher myeloid differentiation and a good response to chemotherapy. M2 patients with t(8;21) could be distinguished on a number of hematological parameters, eg white blood cell count and percentage of bone marrow myeloblasts and promyelocytes, from RAEB-T carrying the t(8;21). Based on these findings we suggest that leukemia patients carrying t(8;21) can be grouped into two types; overt acute myeloid leukemia (M2) and smoldering or slowly evolving myeloid leukemia.
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PMID:High degree of myeloid differentiation and granulocytosis is associated with t(8;21) smoldering leukemia. 763 Jan 88

Myelodysplastic syndromes (MDS) are clonal disorders of the multipotent hematopoietic stem cell characterized by ineffective hematopoiesis and associated with marrow hypercellularity, increased intramedullary cell death and peripheral cytopenias of varying severity. Patients with myelodysplasia have a propensity (20% to 30% of cases) to undergo transformation into acute myeloid leukemia (AML), and a large body of evidence indicates that MDS represent steps in the multiphasic evolution of AML. Progression of the disease is characterized by expansion of the abnormal clone and inhibition of normal hematopoiesis leading to deterioration of the blood cell count and/or development of AML. MDS are relatively unusual in childhood, representing only 3% of pediatric hematological malignancies, although it has been reported that up to 17% of pediatric AML cases may have a previous myelodysplastic phase. The first systematic attempt at morphological classification of MDS was provided by the French-American-British (FAB) group. However, the FAB classification of MDS is only partially applicable in children. Some variants are extremely rare or absent (refractory anemia with ring sideroblasts and chronic myelomonocytic leukemia), and other peculiar pediatric disorders, represented by juvenile chronic myelogenous leukemia (JCML) and the monosomy 7 syndrome, are not included. Moreover, since there is a partial overlap between pediatric MDS and myeloproliferative disorders and the variants occurring in young children have rather specific features, some confusion still surrounds the nosographical definition of childhood MDS, so that none of the proposed classifications are widely accepted and used. Characteristically, some genetic conditions such as Fanconi's anemia, Shwachman's and Down's syndromes predispose to the development of MDS in childhood. The most common variants of childhood MDS are represented by JCML and the monosomy 7 syndrome, both disorders typically occurring in young children. JCML is characterized by a spontaneous growth of granulocyte-macrophage progenitors that show a striking hypersensitivity to granulocyte-macrophage colony-stimulating factor. Clinical presentation resembles that of some myeloproliferative disorders, with massive organomegaly usually not observed in the classically reported variants of MDS. Clinical features of the monosomy 7 syndrome resemble those observed in JCML and a differential diagnosis between these two entities relies upon the higher percentage of fetal hemoglobin, the more pronounced decrease in platelet count and, in some cases, the lack of the peculiar cytogenetic abnormality in the latter. With the number of children being cured of cancer constantly rising, a significant increase in secondary or chemotherapy-related myelodysplasia is being observed, and these disorders represent a formidable challenge for pediatric hematologists due to their poor response to chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Myelodysplastic syndromes: the pediatric point of view. 767 22

Steel factor (SLF, c-kit ligand), a potent costimulating cytokine in vitro for myeloid progenitor cells from normal donors, is currently being evaluated in clinical trials for effects on hematopoiesis. Based on a preliminary observation that colony-stimulating factor (CSF)-responsive myeloid progenitor cells (CFU-GM) from a few patients with acute myeloid leukemia (AML) did not respond to the costimulating effects of SLF, we evaluated responsiveness of bone marrow or blood CFU-GM from 26 patients with either AML, chronic myeloid leukemia (CML) or myelodysplastic syndrome (MDS) to the effects in vitro of SLF and/or granulocyte-macrophage CSF (GM-CSF). Cells from all 26 patients responded to the stimulating effects of GM-CSF, but marked heterogeneity was detected in each disease category to the costimulating effects of SLF. Nine of 13 patients with AML, 2 of 6 patients with CML and 4 of 7 patients with MDS had clonogenic cells that did not respond significantly to the costimulating effects of SLF. In a more limited study of cells from patients with MDS, it was noted that if the CFU-GM of that patient did not respond to SLF enhancement of CSF-induced colony formation, neither did the erythropoietin (Epo)-dependent erythroid (BFU-E) or multipotential (CFU-GEMM) cells of that patient (3 cases of refractory anemia [RA] evaluating bone marrow and in 1 case blood progenitors as well). If CFU-GM responded, BFU-E and CFU-GEMM responded (bone marrow from 1 patient with chronic myelomonocytic leukemia [CMMol]). Clinical criteria did not readily distinguish between patients who had SLF-responsive vs. -nonresponsive clonogenic cells. While the mechanistic reason for this heterogeneity in responsiveness is not clear, these differences should be carefully considered for possible clinical trials with SLF in patients with acute and chronic myeloid leukemia and MDS.
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PMID:Differential responses of myeloid progenitor cells from patients with myeloid leukemia and myelodysplasia to the costimulating effects of steel factor in vitro. 768 84

The ability of induction of differentiation of leukemia cells was first proved by cultured leukemia cells, and such ability has been also confirmed clinically as a result of observation of the dramatic effect of all-trans retinoic acid on acute promyelocytic leukemia and the usefulness of low-dose of ara-C therapy for acute myeloid leukemia. We studied differentiation induction of primary cultured bone marrow cells from myelodysplastic syndrome (MDS) patients by ara-C and VP16 with or without addition of G-CSF. We also studied clinical efficacy of differentiation therapy in 56 patients with MDS. Differentiation induction effects were observed in 3 of 14 patients treated with G-CSF in combination with low-dose of ara-C or low-dose of VP16. In addition, high-dose methylprednisolone therapy, GM-CSF and anabolic steroid therapy also showed similar effect on refractory anemia, even in a few patients. Since these results suggested the usefulness of differentiation therapy of MDS, it is earnestly hoped that more effective therapy, including a concomitant use of cytokine, might be established as soon as possible.
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PMID:[Differentiation therapy for myelodysplastic syndrome]. 768 64

240 patients with MDS studied cytogenetically at diagnosis between 1981 and 1990 were followed until death or until April 1992 to evaluate the prognostic significance of FAB classification, age and karyotype. 61 patients (25.4%) subsequently transformed into AML and 176 (73.3%) died during the follow-up period. Patients with blastic MDS types had a shorter survival and a higher probability of leukemic transformation. The younger age increased the probability of leukemic transformation, but was associated with a longer survival. The absence of analyzable mitoses was associated with a shorter survival. The complex chromosomal abnormalities at the initial evaluation identified a subgroup of patients with a high risk of a short survival and/or subsequent leukemia transformation. In refractory anemia the presence of complex chromosomal abnormalities was linked with a relative risk of 3.58 of leukemic transformation and shorter survival as compared with other cytogenetically defined groups.
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PMID:Karyotype at diagnosis, subsequent leukemic transformation and survival in myelodysplastic syndrome. Czechoslovak MDS Cooperative Group. 776 30

The c-mpl gene encodes a member of the hematopoietic cytokine receptor superfamily. This gene was discovered through the study of a murine retrovirus which induces an acute myeloproliferative syndrome in mice. MPLV (for myeloproliferative leukemia virus) has transduced a truncated and constitutively activated form of the c-mpl receptor chain. The c-mpl ligand is unknown, but recent data indicate that it could specifically regulate thrombocytopoiesis. This review focuses on the expression of the c-mpl gene in a large series of human hematopoietic pathologies by Northern blot analysis. Barely detectable transcript levels were detected in normal bone marrow (BM) and in BM samples from chronic myeloproliferative disorders, plasmocytoma, Burkitt lymphoma or acute lymphoid leukemia. In contrast, high levels of c-mpl expression were detected in 45% of acute myeloid leukemia (AML). No correlation was found between c-mpl expression and the French-American-British classification subtype of AML. However c-mpl expression correlated with CD34 expression, and unfavorable cytogenetic abnormalities, defining a subgroup of AML with a low rate of complete remission. In myelodysplasia, c-mpl expression was elevated in 44% of chronic myelomonocytic leukemia (CMML), 42% of refractory anemia with excess myeloblasts (RAEB), and RAEB in transformation to acute leukemia (RAEBt), but not in refractory anemia (RA) and RA with ringed sideroblasts (RARS). In CMML, there was no correlation between c-mpl expression and any prognostic factor tested, nor with the course of the disease. The biologic significance of c-mpl expression in RAEB and RAEBt is probably different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:c-mpl expression in hematologic disorders. 777 60

In a study of 94 patients with myelodysplastic syndrome (MDS) associated vasculitis was observed in 5, which preceded hematologic diagnosis in 4. Leukocytoclastic vasculitis was observed in 5 cases being associated to lobular panniculitis in one. Three patients had refractory anemia, one sideroblastic anemia (SA) and another refractory anemia with excess blasts (RAEB). In the latter case lymphomatoid papulosis was also observed which, to date, has not been previously described in association with MDS. Another case presented seronegative polyarthritis and renal disease coinciding with vasculitis. Polyarteritis nodosa was diagnosed in a third patient in agreement with the criteria of the American College of Rheumatology, the association of which with MDS is exceptional. In the same case medullary cytogenetic study showed 46, XY,t (12;20), an abnormally which has not been described to date in cases of MDS. All the cases were treated with glucocorticoids in addition to cyclophosphamide in the patient with polyarteritis nodosa, with an improvement in the vasculitis being observed in all the patients. Two patients died, one (SA) due to pneumonia and the other (RAEB) due to subdural hematoma following transformation to acute myeloblastic leukemia. With 5% of the MDS studied presenting vasculitis, this syndrome should be included in the differential diagnosis of vasculitis observed in patients with cytopenia.
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PMID:[Vasculitis associated with a myelodysplastic syndrome: a report of 5 cases]. 779 67

We performed X-linked restriction fragment length polymorphism (RFLP)-methylation analysis to study the clonality of hematopoiesis in five patients with myelodysplastic syndromes (MDS), who had responded to chemotherapy. Two patients had MDS in blast crisis, two had refractory anemia with an excess of blasts in transformation (RAEB-T), and one had acute myelogenous leukemia with trilineage myelodysplasia (AML-TMDS). Following the administration of low-dose cytarabine therapy or of conventional intensive chemotherapy, we observed a reversion to polyclonal hematopoiesis in three patients who achieved a complete remission (CR). Polyclonal hematopoiesis persisted in one patient in CR, and monoclonal hematopoiesis persisted in another patient of minor response. These results indicate that polyclonal hematopoiesis can be restored in some MDS patients who achieved CR. We are encouraged, therefore, to administer intensive consolidation chemotherapy to prolong the duration of remission.
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PMID:Recovery of polyclonal hematopoiesis in patients with myelodysplastic syndromes following successful chemotherapy. 791 Feb 21


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