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)

Drug resistant cells often have an increased capacity to repair their DNA after damage by cytotoxic agents. Aphidicolin can inhibit this DNA repair. We describe a study of the effect of aphidicolin to modulate the sensitivity to cytotoxic drugs of blast cells from 13 patients with AML, 11 with de novo disease on presentation and 2 secondary to MDS. Three patients had relapsed following previous therapy and samples were received from 1 patient both on presentation and relapse. Blast cells were exposed to anthracyclines, antimetabolites or etoposide +/- aphidicolin (15 microM) for 48 hours. The MTT assay was used to measure cell survival and the LC50 (concentration of drug required for 50% cell kill) was calculated. Overall, there was a significant increase in sensitivity to ara-C on co-incubation with aphidicolin in 12/14 samples (p = 0.007). The median increase in sensitivity was 3.88-fold (range 1.26- to 80-fold). Interestingly, when patients were grouped according to in vitro sensitivity to ara-C, cells from resistant patients demonstrated the greatest increase in sensitivity (median 14-fold compared to 2-fold for the sensitive group, p = 0.02). Despite the documented evidence for altered DNA repair as a mechanism of resistance to the topoisomerase II inhibitors, we found no significant increase in sensitivity to daunorubicin, doxorubicin or etoposide on co-incubation with aphidicolin. Nevertheless, we believe the unparalleled modulation of ara-C warrants further investigation.
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PMID:Aphidicolin markedly increases the in vitro sensitivity to ara-C of blast cells from patients with AML. 1050 Aug 35

Little is known of the functional status of blast cells from patients with acute myeloid leukaemia (AML). We have studied phagocytosis and membrane receptors by flow cytometry (FCM), and secretory activities in blast cells from 24 AML patients prior to treatment. Blast cells from 11/16 patients attached N. meningitidis, and internalization occurred in 7/14. The phagocytosis of zymosan particles and N. meningitidis correlated linearly (r = 0.9, p<0.01, n = 11). Surface membrane expression of CD32 and CD11b was sufficient to account for opsonin-dependent attachment in all except one patient. A significant fraction of the blast cells attached, but did not internalize meningococci. CD32 and CD11b were non-functional in all the blasts from five patients, and in a subpopulation from seven additional patients. Significantly more large than small blasts expressed CD32, CD35 and CD11b (p<0.001). Phagocytosis was unrelated to the secretion of IL-1alpha, IL-1beta, and TNFalpha. In conclusion, AML blast cell function is related to receptor expression, cell size and granularity, and to FAB-type.
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PMID:Functional differentiation of acute myeloid leukaemia blast cells. 1059 75

The results of study of morpho-cytochemical peculiarities, antigenic profile and peripheric blood and/or bone marrow blast cell karyotype of 21 patients with acute myeloid leukemia are presented. Hemopoietic cell immunophenotyping was carried out with the use of cytofluorometer FACScan and chromosome cytogenetic analysis with the use of analyzer "Metascan". It has been shown that in the AML M1 blast cell plasmatic membrane carries pan-myeloid CD33 and CD13 antigens, the last having high density of expression, and the CD38 antigen, which is a myeloid cell-precursor marker. In these patients tetraploidy, being the testimony of karyotype change, has been ascertained. It has been found out that the AML M2 blasts, except pan-myeloid antigens, express the cell proliferation CD71 marker. Blast cell karyotype peculiarities typical for this leukemia sub-variant have been revealed. In patients with the AML M4 in 3 of 6 cases an anomalous karyotype has been found. It has been also shown that the CD14 antigen, and rather its percentage in blast total population, is the differential-diagnostic criterion for the AML M4 and M5.
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PMID:[The immunophenotypic and cytogenetic characteristics of the blast cells in subvariants of acute myeloid leukemia]. 1080 42

Blast cells from patients with acute myeloid leukemia (AML) commonly express CD64, the high-affinity receptor for immunoglobulin G (FcgammaRI). An immunotoxin (MDX-44) was constructed by coupling humanized anti-CD64 monoclonal antibody (mAb) H22 via a bivalent linker to deglycosylated ricin A-chain (RA). Human leukemia cell lines were incubated with MDX-44 or H22/free RA. The effect of MDX-44 on the proliferation of leukemia cells was assessed by [(3)H]thymidine incorporation. In the presence of interferon-gamma (IFN-gamma), MDX-44 significantly inhibited the proliferation of CD64(+) HL-60, NB4, and U937 cells in 72-h cultures in a dose-dependent manner. The mechanism of action appeared to be the induction of apoptosis, as measured by propidium iodide staining and flow cytometry analysis. However, CD64(-) KG-1a and Daudi cells were not affected by MDX-44/IFN-gamma. Incubating HL-60 cells with MDX-44/IFN-gamma resulted in a 99% decrease in colony-forming units, whereas colony-forming cells in normal bone marrow were not significantly suppressed by such treatment. Cells from 60% of AML patients (6/10) were inhibited by MDX-44/IFN-gamma, and the inhibition was correlated with CD64 expression on these cells (r = 0.65). In a human AML model in NOD/SCID mice, MDX-44/IFN-gamma inhibited 95-98% of peritoneal exudate AML cell proliferation and 85-90% of solid leukemia masses. The effect of MDX-44 on AML cells was dependent on activation of cells by IFN-gamma. MDX-44/IFN-gamma may have value in the therapy of AML cells expressing cell-surface CD64.
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PMID:Cytotoxicity of anti-CD64-ricin a chain immunotoxin against human acute myeloid leukemia cells in vitro and in SCID mice. 1127 63

This study retrospectively analyses the experience with an intensive enteral feeding protocol in children undergoing BMT at the National Paediatric BMT Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin. Fifty-three patients were transplanted between January 1996 and December 1998; 42 patients received allogeneic transplants, (19 unrelated) and 11 were autologous. Indications included ALL (21), ANLL (3), CML (3), JCML (1), MPS (5), WAS (2), AA/FA (6), NHL/HD (3) and solid tumours (9). Nasogastric (NG) tubes were inserted electively either during conditioning or within the first week when voluntary oral intake had decreased. Nineteen patients were commenced on a whole protein-based formula, 28 on a semi-elemental preparation and two were commenced on an elemental feed. All were maintained on an elemental formula during the period of maximal gut toxicity. Tubes which were vomited were promptly replaced and morphine infusions were routinely employed until mucositis had resolved. Of 49 evaluable patients, 42 (86%) were maintained exclusively on enteral nutrition and seven required parenteral nutrition. Seven patients weighed <85% ideal body weight (IBW) at discharge (range 75-84), only one of whom was <85% IBW at 3 months. Twenty-two patients continued on NG feeds following discharge (median 41 days). No patient had veno-occlusive disease. The programme was overwhelmingly endorsed by patients and/or parents but required intensive multidisciplinary counselling to ensure success.
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PMID:Intensive enteral nutrition support in paediatric bone marrow transplantation. 1136 Jan 15

Earlier studies have revealed undernotification of hematological malignancies in Swedish and other Cancer Registries. We present epidemiological data on AML, ALL and unspecified AL in adults diagnosed 1987-1992 in a well-defined population. Blast crises of CML were excluded. The Swedish Cancer Registry and Cause of Death Registry were compared and patient records reviewed for validation. When available, listings of pathology bone marrow reports and inpatient discharge diagnoses were utilized for casefinding. 260 cases of acute leukemias could be verified in a population of 663,135 adults, corresponding to a yearly incidence of 6.5/100,000. The median age of the patients was 69.2 years. 214 cases were AML, 38 ALL and eight unspecified AL. Undernotification in the Cancer Registry was found to be 15.4%, greater for AML and unspecified AL than for ALL. In addition the coding was not uniform, resulting in an incidence rate in adults of 5.3/100,000 for the Cancer Registry which is 18.5% lower than that of our study. A significant survival advantage was seen for notified patients. Combination of the Cancer Registry and Cause of Death Registry gave acceptable coverage, omitting only four patients. As the incidence of acute leukemias in our study is comparatively high, we hypothesize that underestimation of incidence and overestimation of survival are general problems for cancer registries.
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PMID:Adjustment of incidence rates after an estimate of completeness and accuracy in registration of acute leukemias in a Swedish population. 1137 73

Myelodysplastic syndrome (MDS) is a slowly progressing hematologic malignancy associated with a poor outcome. Despite the relatively high incidence of MDS in the elderly, differentiation of MDS from de novo acute myeloid leukemia (AML) still remains problematic. Identification of genes expressed in an MDS-specific manner would allow the molecular diagnosis of MDS. Toward this goal, AC133 surface marker-positive hematopoietic stem cell (HSC)-like fractions have been collected from a variety of leukemias in a large-scale and long-term genomics project, referred to as "Blast Bank," and transcriptome of these purified blasts from the patients with MDS were then compared with those from AML through the use of oligonucleotide microarrays. A number of genes were shown to be expressed in a disease-specific manner either to MDS or AML. Among the former found was the gene encoding the protein Delta-like (Dlk) that is distantly related to the Delta-Notch family of signaling proteins. Because overexpression of Dlk may play a role in the pathogenesis of MDS, the disease specificity of Dlk expression was tested by a quantitative "real-time" polymerase chain reaction analysis. Examination of the Blast Bank samples from 22 patients with MDS, 31 with AML, and 8 with chronic myeloid leukemia confirmed the highly selective expression of the Dlk gene in the individuals with MDS. Dlk could be the first candidate molecule to differentiate MDS from AML. The proposal is made that microarray analysis with the Blast Bank samples is an efficient approach to extract transcriptome data of clinical relevance for a wide range of hematologic disorders.
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PMID:Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction. 1143 12

Granulocytic sarcoma is an extramedullary solid tumour consisting of myelogenous leukaemic blast cells, usually seen in acute myeloid leukaemia and less commonly in patients with chronic myeloid leukaemia or myeloproliferative disorders. Blast cells have a predilection for periosteal and perineural regions and rarely precede evidence of systemic disease. We present two patients, aleukaemic on peripheral blood counts, both at presentation and during subsequent treatment. We present the MRI features of this rare but important condition.
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PMID:MRI of perineural extramedullary granulocytic sarcoma. 1146 64

alpha- and beta-tryptase genes encode serine proteases that are abundantly expressed by mast cells. Under physiologic conditions other myeloid cells are virtually tryptase negative. However, tryptases are also expressed in several myeloid leukemia cell lines. In this study, serum total tryptase levels were determined in 150 patients with acute leukemias (de novo acute myeloid leukemia [AML], n = 108; secondary AML, n = 25; acute lymphoid leukemia [ALL], n = 17) by fluoroenzyme immunoassay. In healthy subjects (n = 30), tryptase levels ranged between 2.0 and 12.6 ng/mL. Elevated tryptase levels (> 15) were detected in 42 (39%) of 108 patients with de novo AML and in 11 (44%) of 25 patients with secondary AML. No elevated tryptase levels were found in patients with ALL. In de novo AML, elevated tryptase levels were frequently detected in patients with French-American-British classification M0 (6 of 9), M2 (9 of 14), M3 (4 of 6), and M4eo (7 of 7), and less frequently in M1 (7 of 20), M4 (6 of 26), M5 (2 of 18), M6 (0 of 5), or M7 (1 of 3). The highest tryptase levels were found in M4eo. Immunohistochemical staining of bone marrow sections with anti-tryptase antibody as well as immunoelectron microscopy revealed tryptase expression in the cytoplasm of myeloblasts. As assessed by Northern blotting and reverse transcriptase-polymerase chain reaction, AML cells expressed alpha-tryptase messenger RNA (mRNA) but little or no beta-tryptase mRNA. In AML patients with elevated serum tryptase before chemotherapy, who entered complete remission, tryptase levels returned to normal or near normal values. Blast cell persistence or regrowth was associated with a persistently elevated level or recurrent increase of tryptase. Together, tryptase is expressed in myeloblasts in a group of AML and may serve as a useful disease-related marker.
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PMID:Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia. 1156 8

Between 1992 and 1999, 5 patients with chronic idiopathic myelofibrosis (MF) underwent splenectomy at our hospital. The median age at the time of splenectomy was 63 years (range, 58-69 years), while the median interval from diagnosis of MF to splenectomy was 38.2 months (range, 3.7-87.2 months). Reasons for splenectomy included symptomatic splenomegaly in 5 patients, transfusion-dependent anemia in 5, and refractory thrombocytopenia in 3. Although most of the patients with transfusion-dependent anemia and thrombocytopenia showed some improvement at 1 month after splenectomy, the response was durable in only 2 patients at 6 months. Post-surgical thrombocytosis of 1020 x 10(9)/l was observed in one patient. Blast cell counts in peripheral blood increased after splenectomy in 4 patients. Leukemic transformation occurred in one patient 5 months after splenectomy. Four patients eventually died (2 of infection, 1 of acute myelocytic leukemia, and one of heart failure). Overall median survival was 54.7 months (range, 10.9-110.0 months) and 10.2 months (range, 6.0-33.6 + months) from diagnosis and time of splenectomy, respectively. We confirmed the palliative role of splenectomy in advanced-stage MF, but sufficient consideration should be given to late complications including blastic transformation.
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PMID:[Splenectomy in 5 patients with idiopathic myelofibrosis]. 1157 2


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