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)

Evidence supporting the view that eosinophilic leukemia exists as a separate entity among myeloproliferative disorders was found in the pathological and histochemical findings in a case of hypereosinophilic disease. Blast cells and eosinophils in all stages of maturity, including unusual atypical eosinophil precursors, were seen in a prominent infiltration of the spleen and the liver. Blasts were far more numerous in the viscera, especially in the liver, than in the marrow and peripheral blood. Enzyme histochemical studies of plastic sections showed that blasts were reactive for cyanide-resistant peroxidase, which is specific for eosinophils, and could therefore be regarded as part of an eosinophilic leukemic proliferation. Some eosinophils showed aberrant reactivity for chloroacetate esterase. The existence of a neoplastic proliferation of eosinophils is consistent with the view that eosinophils represent a distinct marrow line. The possibility that hypereosinophilic patients may harbor a far more prominent blastosis in the viscera than is apparent from marrow and blood picture is also stressed. Finally, a chromosomic abnormality previously described in acute nonlymphocytic leukemia with atypical eosinophils in the marrow is for the first time reported in a patient with hypereosinophilic disease.
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PMID:Eosinophilic leukemia with prominent visceral involvement: histopathological and histochemical observations. 640 Jan 94

Flow-cytometric analysis of bone marrow aspirates and blood samples was performed in 106 adult patients with acute leukemia in order to assess the size and the prognostic significance of the percentage of S-phase cells in the bone marrow (%Sbm). A correction procedure was applied for the fraction of contaminating peripheral nucleated cells in bone marrow aspirates (%Fpb). In 82 out of 106 patients studied, the %Sbm could be reliably determined, and was compared to the %Sbm in 25 healthy controls. The %Sbm in these healthy controls ranged from 8.4 to 14.6%. The median %Sbm in 31 patients with acute nonlymphocytic leukemia (ANLL) at diagnosis (11.3%) and in 14 patients with ANLL at relapse (11.8%) did not differ significantly from the median %Sbm in normal bone marrow (11.7%). On the other hand, in 12 out of 23 patients with acute lymphocytic leukemia (ALL) at diagnosis and in 6 out of 11 patients with ALL at relapse the %Sbm was much higher and ranged from 17.8 to 44.0%. The prognosis of patients with ALL with a high %Sbm (greater than 15%) was significantly worse. Blast cells with an abnormal DNA content (aneuploid cells) were noticed in 7.7% of the patients with acute leukemia at diagnosis. This incidence, however, was significantly higher in ALL patients at relapse (i.e. 42.1%).
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PMID:Flow cytometric determination of the S-phase compartment in adult acute leukemia. 641 61

Both cytogenetic abnormalities and in vitro growth patterns of leukemic cells have prognostic significance in acute nonlymphocytic leukemia (ANLL). The present study was undertaken to analyze the interrelationship between these two factors and response to therapy. Blast cells from 43 patients with de novo ANLL, four patients with secondary ANLL, and two patients with ANLL following a preleukemic phase were studied using both in vitro culture in methylcellulose and quinacrine chromosome banding techniques. In 19 patients with de novo ANLL, minimal growth in culture (less than or equal to 5 colonies without prominence of small clusters) was noted (Pattern I). Blast cells from the remaining 24 patients formed numerous abnormal clusters and colonies in a continuum distribution (Pattern II). Sixty-three percent of Pattern I patients had completely normal karyotypes (NN). Only 29% of Pattern II patients were NN. No Pattern I patient had only abnormal karyotypes (AA), while 25% of Pattern II patients were AA (p less than 0.05). All six patients with secondary leukemia or leukemia following a preleukemic phase demonstrated both Pattern II growth and cytogenetic abnormalities. Fifty-six percent of Pattern I patients with de novo ANLL responded to chemotherapy, 35% of Pattern II patients responded, and 0% of patients with secondary or post-preleukemic ANLL responded. The correlation between the presence of cytogenetic abnormalities in leukemic cells and a pattern of excessive, abnormal growth in vitro coupled with the trend toward poor prognosis in these patients suggests that cytogenetically abnormal cells may have a proliferative advantage both in vitro and in vivo.
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PMID:Correlation of in vitro culture pattern and Q-banded karyotype in acute nonlymphocytic leukemia. 683 67

Blast cells from patients with Acute Myeloblastic Leukemia (AML) were separated according to cell size using velocity sedimentation under unit gravity. Fractions obtained in this way were plated in methyl cellulose with a growth stimulator present in media conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM). Colonies of blast cells form under these conditions. Pooled cell suspensions from such colonies were plated in microwells; the plating efficiency of such suspensions is a measure of blast progenitor self-renewal occurring in the original blast colonies. Self-renewal assays on each fraction indicated that self renewal among blast progenitors is heterogeneously distributed with subpopulations differing in renewal capacities. The results are consistent with the view that blast cell subpopulations in AML undergo a series of transitions associated with decreasing self renewal capacity, analogous to that observed in normal hemopoiesis, where proliferative capacity decreases with increasing differentiation.
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PMID:The cellular basis of self renewal in culture by human acute myeloblastic leukemia blast cell progenitors. 692 77

Antigenic compounds from the surface of leukemic myeloblasts are shed in vitro on short-term culture. Blast cells radiolabeled by lactoperoxidase iodination release soluble compounds that react immunologically with alloantisera to leukemia-associated antigens. Partially characterized soluble antigens were used to raise heteroantisera in monkeys that are selectively reactive with leukemic myeloblasts and unreactive with nonleukemic cells. Monkey heteroantisera were used to further characterize soluble leukemia antigens. Sera from patients with acute myeloblastic leukemia inhibit the reactivity of the heteroantisera, suggesting that soluble leukemic antigen is released in vivo as well.
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PMID:Acute myeloblastic leukemia-associated antigens: detection and clinical importance. 694 35

The current study was undertaken to determine the relevance of leukemic blast cell proliferative activity, cellular parameters of Ara-C metabolism and the in vitro sensitivity to GM-CSF in association with the clinical response to TAD-9 induction therapy in 66 patients with de novo acute myeloid leukemia (AML). Proliferative activity was assessed by 3H-thymidine (3H-TdR) incorporation and thymidine kinase (TK) activity, parameters of Ara-C metabolism comprised the activities of deoxycytidine kinase (DCK) and DNA polymerase alpha (poly alpha) as well as Ara-CTP concentrations and 3H-Ara-C uptake into DNA. GM-CSF sensitivity was determined by in vitro incubation of blasts for 48 h with or without GM-CSF (100 U/ml) followed by an additional 4 h concurrent exposure to GM-CSF and 3H-TdR (0.5 microCi/ml). The following results were obtained as expressed by median values and ranges: 3H-TdR incorporation: 1.07 pmol/10(5) cells (0.0-10.1), TK: 7.3 pmol/min/mg protein (1.3-56.0), DCK: 9.3 pmol/min/mg protein (0.77-47.1), poly alpha: 1.7 pmol/min/mg protein (0.00-28.9), Ara-CTP: 53.3 ng/10(7) cells (13.3-211.0), 3H-Ara-C uptake: 0.06 pmol/10(5) cells (0.0-0.57). 3H-Ara-C uptake was correlated with 3H-TdR incorporation (r = 0.74) and with the (S-phase dependent) activities of TK (r = 0.73) and poly alpha (r = 0.71, but not with DCK activity or intracellular Ara-CTP content. Blast cells of 37 from 55 analyzed patients were found to be sensitive to GM-CSF stimulation as defined by an increase in 3H-TdR incorporation > or = 1.5-fold over control values after the 48 h GM-CSF exposure. In vitro data were related with clinical response to TAD-9 induction therapy in 43 patients with newly diagnosed AML, taking the blast cell reduction at day 10 or 16 to < 5% or > or = 5% residual blasts as early parameter for adequate or inadequate response, respectively. While neither 3H-Ara-C uptake, nor intracellular Ara-CTP concentration, TK nor DCK activity were predictive for response, a high 3H-TdR incorporation and a high poly alpha activity were associated with adequate blast cell reduction. Median values of 3H-TdR incorporation were 2.26 pmol/10(5) cells for patients with adequate blast cell clearance and 0.80 pmol/10(5) cells for patients with inadequate blast cell clearance (P = 0.11), the respective values for poly alpha were 3.22 pmol/min/mg protein for responders and 1.1 pmol/min/mg protein for non-responders (P = 0.0085).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Blast cell proliferative activity and sensitivity to GM-CSF in vitro are associated with early response to TAD-9 induction therapy in acute myeloid leukemia. 747 75

The blast progenitors in acute myelogenous leukemia grow in response to hematopoietic growth factors (HGFs), and their sensitivity to antileukemic drugs is influenced by HGFs. We report the effects of stem cell factor (SCF) on the growth and sensitivity to 1-beta-D-arabinofuranosylcytosine (Ara-C) of blast progenitors in acute myelogenous leukemia. SCF stimulated both colony formation and self-renewal of blast progenitors and, when used in combination with other HGFs, synergistic enhancement of colony formation was noted in 8 of the 15 patients examined. Cell fractionation studies demonstrated no unique growth dependency on SCF in either CD34+ or CD34- populations. Blast cells of patients that displayed synergistic growth enhancement with SCF displayed the highest Ara-C sensitivity when HGFs were used in combination with SCF. The tritiated thymidine suicide test (20-min exposure) revealed that the proportion of blast progenitors in the S phase of the cell cycle was highest when SCF and another HGF were simultaneously present, although 24-h exposure killed most or all of the blast progenitors. These data indicate that SCF enhances growth and sensitivity to Ara-C of acute myelogenous leukemia blast progenitors in a closely correlated fashion and that the cell cycle changes as well as other mechanisms are involved in the Ara-C sensitivity modulation by SCF.
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PMID:Combinations of stem cell factor with other hematopoietic growth factors enhance growth and sensitivity to cytosine arabinoside of blast progenitors in acute myelogenous leukemia. 750 23

Blast cells from 70% of patients with acute myeloid leukemia (AML) show some evidence of in vitro autonomous growth, which appears to be related to the autocrine secretion of growth factors, particularly granulocyte-macrophage colony-stimulating factor (GM-CSF). In the majority of cases, the growth factors appear to be involved in classical extracellular autocrine or paracrine loops with neutralizing antibodies to the relevant cytokine inhibiting growth. In a minority, however, antibodies do not inhibit growth despite evidence of secretion of the cytokine. There is evidence for intracellular autocrine loops in murine leukemic cell lines. In this study, we wished to investigate for the presence of such intracellular loops involving GM-CSF in AML blast cells. Blast cells from 11 patients with AML were cultured in the presence of either neutralizing GM-CSF antibody or an antisense oligonucleotide directed against GM-CSF. We also studied the effect of the oligonucleotide on the autonomous growth of cells whose production of GM-CSF had been apparently abolished by either interleukin-1 receptor antagonist (IL-1Ra) or following blast cell purification using the CD34 antigen. The autonomous growth of the blast cells from nine of the 11 patients was inhibited by the antisense oligonucleotide (but not by the control sense oligonucleotide). However, only six of the nine were inhibited by the anti-GM-CSF antibody. Similarly, in one patient whose CD34 purified blast cells continued to show a high degree of autonomous growth but did not produce detectable GM-CSF, growth was inhibited by the antisense oligonucleotide but not by antibody, while in another patient whose cells were inhibited by IL-1Ra with, again, loss of detectable GM-CSF, growth could be further inhibited by the addition of the oligonucleotide but not the antibody. These studies provide evidence that intracellular autocrine loops involving GM-CSF are involved in the autonomous growth of some AML blast cells.
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PMID:Evidence for internal autocrine regulation of growth in acute myeloblastic leukemia cells. 751 89

A 64-year-old woman was diagnosed as having myelodysplastic syndrome (MDS) at 45 months after receiving radiotherapy for advanced carcinoma of the uterine cervix. We chose low dose therapy of SPAC and ACR because of the diagnosis as therapy-related MDS and the existence of radiation colitis. She obtained minor response, but two months later she transformed to AML (M2). The interval between low dose therapies was getting shorter and shorter, so we tried intensive chemotherapy consisting of BHAC, ACR and 6MP. Blast numbers were reduced, but she died of sepsis and intestinal bleeding. The patients of MDS with t(8;21) and the patients of therapy-related AML (tAML) with t(8;21) are very rare. According to the literature, only karyotype is a prognostic factor in AML/MDS with t(8;21). And diagnosis by the criteria of FAB classification is of little value regarding clinical progress. That is to say, if the patient has only t(8;21) or karyotypic abnormalities which are of little value in prognosis, such as the loss of a sex chromosome, it must be treated as de novo AML, but if patient has karyotypic abnormalities such as -5, 5q-, -7, 7q-, and/or multiple (complicated) abnormalities, we must accept that the prognosis is poor and must treat it as ordinary MDS/tAML.
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PMID:[Therapy-related leukemia with t(8;21) initially diagnosed as MDS (RAEB in T)]. 756 9

The wt1 gene is located on chromosome 11p13 and encodes a zinc finger motif-containing transcription factor involved in regulation of growth and differentiation. Its expression was shown during embryonic development in various tissues as well as in a few human malignancies including acute leukemias. Using RT-PCR, we found wt1 gene expression in blast cells of the majority of 150 acute leukemia patients. Particularly, the wt1 transcript was detected in 12 of 14 (86%) pre-pre-B-ALL patients, in 33 of 41 (80%) cALL patients, in 23 of 31 (74%) T-ALL patients, and in 53 of 57 (93%) AML patients. Additionally, mononuclear cells from CML patients expressed the wt1 gene only when diagnosed with blast crisis. In contrast to acute human leukemias, mononuclear cells from reactive bone marrow (n = 4), and peripheral blood of healthy volunteers (n = 20), as well as normal peripheral CD34+ hematopoietic progenitors (n = 6) did not express the wt1 gene at detectable levels. Using the anti-WT1 MoAb 6F-H2 in an immunofluorescence assay on single cell level, we found the translated WT1 protein only in nuclei of leukemia blast cells but not in nuclei of normal CD34+ hematopoietic progenitor cells. Blast cells of 12 of 20 leukemia patients (60%) all tested positive for the wt1 gene expression by RT-PCR displayed a strong nuclear immunofluorescence. Its expression in the majority of human acute leukemias but not in normal mononuclear blood cells and normal CD34+ hematopoietic progenitors qualifies the wt1 gene transcript as a 'pan-acute leukemic' marker probably useful in monitoring minimal residual disease after chemotherapy and in detecting leukemic blast cells in purged or unpurged hematopoietic stem cell preparations intended to be used for autologous bone marrow transplantation.
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PMID:Presence of Wilms' tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias. 759 70


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