Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, two genes, AML1 and ETO have been isolated from the chromosomal breakpoint of t(8;21). In this study, we isolated and identified fusion transcripts from a leukemic cell line carrying t(8;21). We demonstrated by PCR analysis that these transcripts are consistently expressed in fresh leukemic cells with t(8;21). On the other hand, the wild type of ETO is expressed in several hematopoietic cells from different lineage, while the expression of AML1 was present in all hematopoietic cells investigated. These widespread expression suggests these molecules play an essential role in hematopoiesis.
Leukemia 1995 Oct
PMID:Expression of AML1 and ETO Transcripts in hematopoietic cells. 747 8

The AML-1/ETO fusion protein is created by the (8;21) translocation, the second most frequent chromosomal abnormality associated with acute myeloid leukemia. In the fusion protein the AML-1 runt homology domain, which is responsible for DNA binding and CBF beta interaction, is linked to ETO, a gene of unknown function. The primary sequences of the runt homology domain indicates no known DNA binding motifs, but is predicted to contain six beta-strands, two alpha-helices and a nucleotide binding motif. Mutagenesis of AML-1/ETO was performed to delimit the functional domains of the chimeric protein. Most mutations in the runt homology domain that resulted in reduced CBF beta binding also inhibited DNA binding, indicating that the DNA and CBF beta binding sequences are tightly linked. However, these activities were separated by a point mutation of residue 144, within the putative ATP binding motif, which nearly eliminated DNA binding, but did not affect CBF beta binding. Random mutagenesis identified the hydrophobic face of the amphipathic fifth beta-strand, adjacent to the putative ATP binding motif, as critical for both DNA and CBF beta binding. C-terminal deletion mutants of AML-1/ETO indicated that ETO sequences are essential for interference with AML-1B-mediated transcriptional activation, and that residue 540 defines the C-terminal boundary of a potential repression domain. Thus, these mutational analyses define the regions of AML-1/ETO which regulate its function and that may be important in promoting leukemia.
 ...
PMID:Functional domains of the t(8;21) fusion protein, AML-1/ETO. 747 4

The nonrandom chromosomal translocation t(8;21)(q22;q22) can be found frequently in acute myelogenous leukemia with maturation (AML-M2). The breakpoint of this translocation has been cloned and characterized, and fusion transcript AML1/ETO has been identified. Reverse transcription polymerase chain reaction (RT-PCR) can be used to amplify the breakpoint site of AML1/ETO in t(8;21)-positive AML-M2 patients. The chimeric transcript can be detected in all 16 (100%) t(8;21)-positive AML-M2 patients. In all samples, the size of the amplified DNA fragments and pattern of restriction digest were identical, indicating that the t(8;21) translocation breakpoint occurs within a single intron of the AML1 and ETO genes. Interestingly, this fusion transcript was also detected in one of 13 AML-M2 patients without the t(8;21) translocation, indicating that a masked translocation involving chromosomes 8 and 21, exists in AML. Minimal residual disease was detected by semi-nested RT-PCR in all four patients tested, who had been in complete remission for 12, 15, 34, and 52 months, respectively. These results indicate that RT-PCR amplification of the AML1/ETO fusion transcript is a powerful tool for diagnosing and monitoring minimal residual disease in AML-M2 patients.
Leukemia 1994 Jan
PMID:Detection of AML1/ETO fusion transcript as a tool for diagnosing t(8;21) positive acute myelogenous leukemia. 750 93

Rearrangements of the AML-1 gene on chromosome 21 as well as transcriptional expression of AML-1-ETO fusion gene were studied in 35 leukemic patients with t(8;21)(q22;q22). A panel of probes generated from the AML-1 gene regions flanking the breakpoint on chromosome 21 allowed us to detect the rearrangement in 24 out of 29 patients. A specific nested reverse transcriptase/polymerase chain reaction (RT/PCR) was developed to detect the t(8;21), either at diagnosis or as minimal residual disease. PCR amplification products were obtained in ten out of 11 patients investigated, and the sensitivity of the reaction was estimated to be between 1 x 10(4) and 1 x 10(-5) cell. An AML-1 rearrangement was also detected in one patient with 8q- and only one chromosome 21, but without 21q+. This indicated that the molecular rearrangement of the der(8) chromosome is more important than the reciprocal one in the malignant process.
Leukemia 1994 May
PMID:AML-1 gene rearrangement and AML-1-ETO gene expression as molecular markers of acute myeloblastic leukemia with t(8;21). 751 41

The chromosomal translocation t(8;21)(q22;q22) in acute myeloid leukemia (AML) can be detected by a reverse transcription-polymerase chain reaction (RT-PCR) for the chimeric AML1/ETO transcript. We have evaluated the clinical relevance of this method for monitoring and detection of minimal residual disease (MRD) in seven patients who reached a complete hematological remission (CHR) after chemotherapy or autologous bone marrow transplantation (ABMT). Peripheral blood (PB) samples of five patients in first continuous complete remission (CCR) were still PCR-positive at a frequency of 1 in 10(5) cells after 7, 8, 8, 10 or 66 months. Chemotherapy led to a reduction from first- to second-step PCR-positivity in three serially monitored patients. AML1/ETO mRNA was also detected in the PB of two patients in CCR, 10 or 12 months after ABMT. PB and bone marrow (BM) showed identical results in all samples tested simultaneously. AML1/ETO fusion transcripts were neither found in the PB and BM of a healthy individual, nor in the PB of a patient after allogeneic BMT for cytogenetically proven t(8;21)-leukemia. Our results indicate the presence of cells carrying the AML1/ETO rearrangement in the PB and BM of all patients in CHR after chemotherapy or ABMT for t(8;21)-positive AML. While this finding raises interesting questions about the biology of acute leukemia, it limits the value of the AML/ETO RT-PCR for the prediction of impending relapse.
Leukemia 1994 May
PMID:AML1/ETO fusion mRNA can be detected in remission blood samples of all patients with t(8;21) acute myeloid leukemia after chemotherapy or autologous bone marrow transplantation. 751 42

The 8;21 chromosomal translocation involves the AML1 gene on chromosome 21 and the ETO gene on chromosome 8 and results in the transcription of a chimeric message. This translocation is most often associated with acute myelogenous leukemia with maturation (AML-M2). The leukemic cells of patients carrying t(8;21) often exhibit several characteristic morphologic features. We identified four cases in which the morphology led us to suspect a t(8;21), but in which this translocation was not observed by cytogenetic analysis. In two of the four cases, an AML1/ETO chimeric fragment was detected by reverse transcription and polymerase chain reaction (RT-PCR), and its sequence was found to be identical to that from patients with a cytogenetically proved t(8;21). Marrow specimens of the four patients lacking the t(8;21) cytogenetically were reviewed retrospectively with regard to seven morphologic features commonly reported to be associated with this translocation, and the results were compared to 13 morphologic controls with the t(8;21). Although none of the 13 controls had all of the characteristic morphologic features, all had at least six, as did the two t(8;21)-negative but RT-PCR-positive patients. The two patients who lacked the t(8;21) and who were RT-PCR-negative showed only three and four of these morphologic features, respectively. Both of the RT-PCR-positive patients had deletions of the long arm of chromosome 9, a common change associated with a t(8;21), supporting our assessment of these patients as having a cytogenetically undetected t(8;21).
Leukemia 1994 Sep
PMID:Correlation between cell morphology and expression of the AML1/ETO chimeric transcript in patients with acute myeloid leukemia without the t(8;21). 752 91

Patients with acute myeloid leukaemia with maturation (AML-M2) that carried the t(8;21) were tested for the presence of chimeric AML1/ETO mRNA. After RT-PCR, an expected band of 208 bp was observed on gel, as well as some slower migrating bands. The base composition of one of the additional products was determined and was found to contain a new 68-bp ETO sequence present at the fusion of AML1 and ETO genes. The derived protein sequence results in a truncated AML1 gene still containing the putative DNA binding domain. Molecular diversity in the AML1-ETO transcripts will have consequences for the detection of minimal residual disease and antisense studies.
Leukemia 1994 Oct
PMID:Molecular diversity in AML1/ETO fusion transcripts in patients with t(8;21) positive acute myeloid leukaemia. 752 1

Peripheral blood stem cells (PBSC) have been used increasingly for haemopoietic reconstitution after marrow-ablative chemotherapy in patients with acute leukaemia because of the possibility that there is a lower risk of leukaemic contamination. We have developed a titration assay using a competitive reverse transcriptase polymerase chain reaction (RT-PCR) which is able to estimate the number of AML1/ETO transcripts so that minimal residual disease (MRD) can be monitored quantitatively in patients with t(8;21) acute myelogenous leukaemia (AML). Using a qualitative RT-PCR method, AML1/ETO transcripts could be detected in all samples from 15 first PBSC harvests and 11 second PBSC harvests obtained from 15 patients with t(8;21) AML. With our competitive RT-PCR assay, the number of AML1/ETO transcripts was found to be lower in the second PBSC harvest than that in the first in every individual. Furthermore, MRD in PBSC harvests was less than that in the corresponding bone marrow obtained on the day of PBSC collection in the individual patients studied. In 10 patients who received autologous blood stem cell transplantation (ABSCT), we could not find a relationship between the number of AML1/ETO transcripts in the infused PBSC harvests and the clinical outcome after ABSCT. The present study clearly indicates that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukaemic cells, the degree of leukaemic contamination may decrease as chemotherapy is repeated. The mobilization of PBSC by repeated chemotherapy may provide an advantageous source of haemopoietic stem cells for ABSCT.
 ...
PMID:Quantitative analysis of AML1/ETO transcripts in peripheral blood stem cell harvests from patients with t(8;21) acute myelogenous leukaemia. 757 20

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.
Leukemia 1995 Jul
PMID:High degree of myeloid differentiation and granulocytosis is associated with t(8;21) smoldering leukemia. 763 Jan 88

The WT 1 gene has been isolated as a tumor suppressor gene of Wilms' tumor. Using reverse transcriptase-polymerase chain reaction (RT-PCR), relative levels of the WT 1 gene expression was examined in 87 patients with acute leukemia, 25 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma (NHL). Significant levels of the WT 1 gene were expressed in all leukemia patients, and for CML the levels increased as the clinical phase progressed. No point mutations were found in the WT 1 gene when samples from 15 acute leukemia patients were subjected to PCR single-strand conformation polymorphism analysis. In striking contrast to acute leukemia, the levels of WT1 gene expression for NHL were significantly low or even undetectable. The levels of WT 1 gene expression inversely correlated with the prognosis of acute leukemia. The quantification of the WT 1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence of absence of tumor-specific DNA markers. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in four patients (two AML-M3 with PML/RAR-alpha, one AML-M2 with AML1/ETO, and one CML with bcr/abl) detected MRD comparable to that obtained from quantitation of WT 1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT 1 or PML/RAR-alpha gene primers were 10(-3)-10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[WT 1 and leukemia]. 764 50


1 2 3 4 5 6 7 8 9 10 Next >>