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)

Seven patients with acute myeloid leukaemia (AML) type M2 and t(8;21), treated with intensive chemotherapy followed in two cases by allogeneic or autologous bone marrow transplant (BMT), were tested for the presence of transcripts of the characteristic chimaeric gene AML1/ETO by reverse transcriptase polymerase chain reaction (RT-PCR) at serial intervals during remission. Six patients, including both BMT patients, demonstrated persistence of t(8;21), one being consistently negative in peripheral blood but bone marrow positive. Bone marrow may, therefore, be more reliable than peripheral blood for detecting residual t(8;21) cells. Our results show persistence of t(8;21) cells in AML-M2 patients following chemotherapy or BMT, some of whom were in long-term remission.
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PMID:Detection of t(8;21) by reverse transcriptase polymerase chain reaction in patients in remission of acute myeloid leukaemia type M2 after chemotherapy or bone marrow transplantation. 799 71

A large number of AML cases is reviewed in order to clarify biological characteristics of t(8;21) AML cells. The incidence of positivities for stem cell antigens, CD34 and HLA-DR, on blasts in t(8;21) AML is higher in comparison with those in other M2 or M3 categories. Frequent expression of CD34 and HLA-DR is indicative of the stem cell derivation of t(8;21) AML cells. The non-blastic leukemic cells in t(8;21) AML tend to lose the immature phenotype with discordant maturation such as low CD33 expression. Further, the blasts show frequent expression of the B-cell antigen, CD19, without other B-cell antigens and immunoglobulin gene rearrangements. AML cells with t(8;21) showed poorer response to granulocyte-macrophage colony-stimulating factor (GM-CSF) due to a decreased number of GM-CSF binding sites. The absence of monocytic differentiation in t(8;21) AML cells might represent the abnormal response to growth factors at the bifurcation stage of granulocyte and monocyte differentiation. Recently, breakpoint region genes for the 8;21 translocation in chromosome 8 and 21 have been isolated, 48-50 and have been named AML1 and ETO, respectively. The AML1 gene showed a strong homology with the Drosophila segmentation gene, runt, which is thought to be necessary for the Sex lethal gene expression. Since the GM-CSF receptor alpha chain gene locates in the pseudoautosomal region of the sex chromosome, the decrease of GM-CSF binding sites might be related to the AML1/ETO fusion gene expression. Further molecular genetic investigations of the breakpoint genes in the future are expected to clarify the unique biological events seen in this type of leukemia.
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PMID:Cellular characteristics of acute myeloblastic leukemia associated with t(8;21)(q22;q22). The Japanese Cooperative Group of Leukemia/Lymphoma. 804 46

The 8;21 translocation, t(8;21)(q22;q22.3), is seen only in acute myelogenous leukemia and is characteristically associated with the M2 subtype. Subsequent to our identification of the t(8;21) breakpoint region on chromosome 21, we reported that the translocation results in the fusion of the AML1 gene on chromosome 21 with a novel gene on chromosome 8 which we called ETO (for eight twenty-one). Recently, the AML1 portion of the fusion protein has been shown to correspond to the DNA-binding and dimerization domains of the mouse gene, polyoma enhancer binding protein 2 alpha B (pebp 2 alpha B). We report here the complete sequence of the ETO portion of the fusion transcript as compiled from complementary DNAs from a t(8;21) AML patient and compare this with the ETO sequence from a mouse brain transcript. The deduced amino acid sequences are 99% identical. ETO has several features consistent with it being a transcription factor. The ETO sequence is different from the portion of PEBP 2 alpha B it replaces in the AML1/ETO fusion protein, except for their common high content of proline, serine, and threonine residues. Because neither the putative zinc fingers nor the TAF110 homology domain of ETO is present in PEBP2 alpha B, one might expect functional differences in the ability of AML1/ETO protein to affect the levels of transcription of genes normally regulated to some degree by AML1 (PEBP2 alpha B) during myeloid differentiation. The relatively high levels of ETO in developing brain suggest that it could be involved in the regulation of some aspect of neural proliferation or differentiation.
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PMID:The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a highly evolutionarily conserved, putative transcription factor. 813 93

A 3-year-old girl developed fever and bilateral exophthalmos. Her initial peripheral blood counts on admission were; Hb8.7 g/dl, Plt. 10.6 x 10(4)/microliters, and WBC 30,890/microliters with 31% peroxidase-positive blasts, some of which contained Auer rods. The bone marrow smears showed 22% blasts with a certain degree of maturation. She was diagnosed as having M2 type AML. Computed tomography revealed bilateral retoro-orbital tumor. The bone marrow karyotype showed no 8;21 translocation but a loss of one sex chromosome. Molecular analysis of the bone marrow cells disclosed rearrangements of the AML1 gene. Chimeric mRNA coded by the AML1-MTG8 gene was also detected by the RT-PCR method. We concluded that this patient had a masked 8;21 translocation in her leukemic cells.
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PMID:[AML1 gene rearrangements, but no 8;21 translocation in a child with acute myeloblastic leukemia (M2)]. 813 4

The t(8;21) translocation is one of the most frequent chromosomal abnormalities in acute myeloid leukaemia and results in gene fusion between AML1 on chromosome 21 and MTG8 (= ETO or CDR) on chromosome 8. AML1 contains a region of sequence homology to the Drosophila runt gene and the mouse polyomavirus enhancer binding protein PEBP2 alpha gene. The rearrangement occurs within a specific intron of the AML1 gene and results in the formation of a chimaeric protein with the consistent feature that the region of sequence homology of AML1 is fused with almost the entire MTG8 protein. MTG8 (ETO, CDR) is predicted to be a transcription activation factor from its sequence with zinc-finger motifs and proline-rich domains. Thus the rearrangement is a fusion between two probable transcription activation factors.
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PMID:Molecular basis of the t(8;21) translocation in acute myeloid leukaemia. 814 22

We describe a 68-year-old patient who developed granulocytic sarcoma of the prostate 9 years after complete remission following successful treatment of acute myelogenous leukemia (FAB, M2). PCR analysis of bone marrow samples in first remission and at the time of relapse detected an AML1/ETO rearrangement typical for AMLs with t (8;21). The CD56 antigen was not expressed on the leukemic cells. Systemic chemotherapy led to a short-lasting regression of the tumor, but the patient subsequently developed overt bone marrow relapse and died during chemotherapy. While granulocytic sarcoma as a primary manifestation of AML is well known, as the first manifestation of relapse it appears to be very uncommon.
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PMID:Granulocytic sarcoma of the prostate as the first manifestation of a late relapse of acute myelogenous leukemia. 814 23

A murine transcription factor, PEBP2, is composed of two subunits, alpha and beta. There are two genes in the mouse genome, PEBP2 alpha A and PEBP2 alpha B, which encode the alpha subunit. Two types of the alpha B cDNA clones, alpha B1 and alpha B2, were isolated from mouse fibroblasts and characterized. They were found to represent 3.8- and 7.9-kb transcripts, respectively. The 3.8-kb RNA encodes the previously described alpha B protein referred to as alpha B1, while the 7.9-kb RNA encodes a 387-amino-acid protein, termed alpha B2, which is identical to alpha B1 except that it has an internal deletion of 64 amino acid residues. Both alpha B1 and alpha B2 associate with PEBP2 beta and form a heterodimer. The alpha B2/beta complex binds to the PEBP2 binding site two- to threefold more strongly than the alpha B1/beta complex does. alpha B1 stimulates transcription through the PEBP2 site about 40-fold, while alpha B2 is only about 25 to 45% as active as alpha B1. Transactivation domain is located downstream of the 128-amino-acid runt homology region, referred to as the Runt domain. Mouse chromosome mapping studies revealed that alpha A, alpha B, and beta genes are mapped to chromosomes 17, 16, and 8, respectively. The last two genes are syntenic with the human AML1 on chromosome 21q22 and PEBP2 beta/CBF beta on 16q22 detected at the breakpoints of characteristic chromosome translocations of the two different subtypes of acute myeloid leukemia. These results suggest that previously described chimeric gene products, AML1/MTG8(ETO) and AML1-EAP generated by t(8;21) and t(3;21), respectively, lack the transactivation domain of AML1.
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PMID:PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials. 816 79

Two genes have been implicated in leukemias of patients with abnormalities of chromosome 3, band q26: EVI1, which can be activated over long distances by chromosomal rearrangements involving 3q26, and EAP, a ribosomal gene that fuses with AML1 in a therapy-related myelodysplasia patient with a t(3;21)(q26.2;q22). AML1 was identified by its involvement in the t(8;21)(q22;q22) of acute myeloid leukemia. Here we report the consistent identification of fusion transcripts between AML1 and EAP or between AML1 and previously unidentified sequences that we named MDS1 (MDS-associated sequences) in the leukemic cells of four patients with therapy-related myelodysplasia/acute myeloid leukemia and in one patient with chronic myelogenous leukemia in blast crisis, all of whom had a t(3;21). In addition, we have identified a third chimeric transcript, AML1/EVI1, in one of the therapy-related acute myeloid leukemia patients. Pulsed-field gel electrophoresis established the order of the genes as EAP, the most telomeric, and EVI1, the most centromeric, gene. The results indicate that translocations could involve multiple genes and affect gene expression over long distances.
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PMID:Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unrelated genes at 3q26 in (3;21)(q26;q22) translocations. 817 Oct 26

The t(3;21)(q26;q22) translocation, which is one of the consistent chromosomal abnormalities found in blastic crisis of chronic myelocytic leukemia (CML), is thought to play an important role in the leukemic progression of CML to an acute blastic crisis phase. The AML1 gene, which is located at the translocation breakpoint of the t(8;21)(q22;q22) translocation found in acute myelocytic leukemia, was also rearranged by the t(3;21)(q26;q22) translocation. Screening of a cDNA library of the t(3;21)-carrying leukemic cell line cells (SKH1) resulted in the isolation of two potentially complete AML1-EVI-1 chimeric cDNAs of 6 kb. Two species of AML1-EVI-1 fusion transcripts of 8.2 and 7.0 kb were detected in SKH1 cells. These cells expressed the 180 kDa AML1-EVI-1 fusion protein containing an N-terminal half of AML1 including a runt homology domain which is fused to the entire zinc finger EVI-1 protein. The AML1-EVI-1 fusion transcript was consistent in all three cases of the t(3;21)-carrying leukemia examined by RNA-based PCR. These findings strongly suggest that the t(3;21) translocation results in the formation of a new class of chimeric transcription factor which could contribute to the leukemic progression of CML through interference with cell growth and differentiation.
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PMID:Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. 831 95

Because limited studies examined effects of transforming growth factor (TGF) beta 1 on growth of human acute myelogenous leukemia (AML) cells, we used factor-dependent and primary AML cells to assess TGF-beta 1 effects on human AML cell growth. OCI-AML1 cells were growth inhibited by TGF-beta 1 regardless of which growth factor was used as a stimulus. In contrast, AML-193 cells were resistant to TGF-beta 1 when grown with or without growth factors. UCSD/AML1 cells were sensitive to TGF-beta 1 inhibition when grown with most cytokines but were relatively resistant to TGF-beta 1 in the presence of macrophage colony-stimulating factor (M-CSF). Although cells grown from 5 of 6 AML patients were inhibited by TGF-beta 1, cells from 1 AML patient were growth stimulated by TGF-beta 1 in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, or mast cell growth factor (kit ligand). Thus, 3 growth patterns with TGF-beta 1 were observed: (a) sensitivity to growth inhibition; (b) resistance; and (c) factor-dependent resistance. Further studies showed that AML-193 and UCSD/AML1 cells expressed type II TGF-beta 1 receptors and that ability of TGF-beta 1 to decrease GM-CSF receptors did not correlate with growth inhibition. AML-193 cells and UCSD/AML1 cells grown with M-CSF could be propagated in 1 ng/ml TGF-beta 1, but UCSD/AML1 cells grown with GM-CSF and TGF-beta 1 died. Morphology and agarose gel analysis of DNA showed UCSD/AML1 cells underwent apoptosis when grown with GM-CSF and TGF-beta 1 but not with M-CSF and TGF-beta 1. Similar studies of OCI-AML1 cells showed that TGF-beta 1 induced apoptosis of cells grown in 5637 bladder cell-conditioned medium or GM-CSF. These studies indicate that human AML cells exhibit heterogeneous growth responses to TGF-beta 1 and that some effects of TGF-beta 1 on myeloid cells occur through programmed cell death.
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PMID:Effects of transforming growth factor beta 1 on growth and apoptosis of human acute myelogenous leukemia cells. 832 49


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