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)

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.
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PMID:AML-1 gene rearrangement and AML-1-ETO gene expression as molecular markers of acute myeloblastic leukemia with t(8;21). 751 41

Disruption of normal p53 expression is the most frequent genetic change occurring in various human solid tumors; it is mostly due to sequence alterations of the p53 coding region by missense mutations or to loss of an entire, functional allele of this gene. In the present study, possible mechanisms resulting in a disruption of regulated expression of wild-type p53 were examined in acute leukemias of either lymphoid (ALL) or myeloid (AML) phenotype. p53 transcript accumulation, nucleotide sequence and gene structure were analyzed in primary leukemic cells from 50 patients. p53-specific transcripts were detected in 26/26 cases of ALL and 16/23 cases of AML using reverse transcriptase (RT)-PCR. Sequencing of transcripts did not reveal any point mutations or deletions. Heterozygosity at a polymorphic Bg/II site within intron 1 was found in 4/28 leukemic samples, and loss of one allele was noted in one of these. In addition, a novel, leukemia-associated structural abnormality located within the 5' flanking region of the p53 gene and associated with the loss of heterozygosity was observed in cells from this patient with ALL. The MDM2 gene which inactivates p53 by binding to it was neither amplified nor rearranged in 28 leukemias studied. Thus, disruption of regulated p53 expression resulting in lack of detectable p53 mRNA even by RT-PCR occurs in about 30% of cases of AML; however, p53 alterations typical for human solid tumors are an infrequent event in most types of human acute leukemias.
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PMID:Mechanisms of p53 alteration in acute leukemias. 752 98

Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine relative levels of transcripts for MDR1 and the recently described multidrug resistance-associated protein (MRP) in normal lymphohematopoietic cells and in 62 bone marrow aspirates of newly diagnosed and recurrent acute leukemia. Levels of MRP expression in newly diagnosed AML samples were similar to those observed in normal bone marrow cells (CD34-negative and CD34-positive) and in unselected HL60 human promyelocytic leukemia cells, which were used as an internal control throughout this study. In contrast, samples of AML obtained at the time of relapse contained approximately twofold higher levels of MRP RNA (P < .01). Analysis of paired samples, the first obtained at diagnosis and the second at relapse, from 13 acute myelogenous leukemia (AML) and four acute lymphocytic leukemia (ALL) patients showed that MRP expression was increased at the time of relapse in greater than 80% of patients. In contrast, no consistent changes of MDR1 expression at relapse were observed. These results raise the possibility that increased MRP expression might contribute to leukemic relapse.
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PMID:Increased expression of the multidrug resistance-associated protein gene in relapsed acute leukemia. 752 66

Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML) that is characterized by the presence of a PML/RAR alpha fusion gene resulting from t(15;17). Peripheral stem cell transplantation (PSCT) has been used to treat patients with AML. To assess the presence of minimal residual disease (MRD) and the contamination of leukemic cells in peripheral stem cells (PSCs), we examined six patients with APL who were undergoing PSCT, using reverse transcriptase polymerase chain reaction analysis to detect the mRNA of the PML/RAR alpha fusion gene. The fusion gene was expressed in the bone marrow cells during the early phase of a complete remission and in some of the PSCs. Detection of the fusion gene can be useful in monitoring for leukemic cell contamination of PSCs and for predicting a relapse of APL.
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PMID:Detection of minimal residual disease by reverse transcriptase polymerase chain reaction for the PML/RAR alpha fusion mRNA: a study in patients with acute promyelocytic leukemia following peripheral stem cell transplantation. 753 17

To understand the clinical implications of transcription factors and their biologic roles during cellular differentiation in the hematopoietic system, we examined the expression of GATA-1, GATA-2, and stem cell leukemia (SCL) gene in human leukemia cell lines and various leukemia patients using the reverse transcriptase-polymerase chain reaction. Cell lines exhibiting megakaryocytic or erythrocytic phenotypes had GATA-1, GATA-2, and SCL gene transcripts, while monocytic cell lines had no detectable GATA-1, GATA-2, or SCL gene mRNA. In some myeloid cell lines, GATA-1 expression, but not SCL gene expression, was detected; GATA-1 expression in HL-60 cells was downregulated during the process of monocytic differentiation. We next examined GATA-1, GATA-2, and SCL gene expression in 110 leukemia samples obtained from 76 patients with acute myeloid leukemia (AML), 19 with acute lymphoblastic leukemia (ALL), and 15 with chronic myeloid leukemia in blast crisis (CML-BC). SCL gene expression was usually accompanied by GATA-1 expression and was preferentially detected in patients with leukemia exhibiting megakaryocytic or erythrocytic phenotypes, while patients with monocytic leukemia were clustered in the group with no detectable GATA-1 expression. None of the patients with ALL or CML-lymphoid-BC expressed SCL. De novo AML patients with SCL gene expression had a lower complete remission (CR) rate and had a significantly poorer prognosis. Among the patients with AML not expressing SCL, a high percentage of patients with CD7+ AML and CD19+ AML had detectable GATA-1, while patients with GATA-1-negative AML had the best CR rate (87.5%). Our results suggest that the expression pattern of transcription factors reflects the lineage potential of leukemia cells, and GATA-1 and SCL gene expression may have prognostic value for the outcome of patients with AML.
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PMID:The expression pattern of erythrocyte/megakaryocyte-related transcription factors GATA-1 and the stem cell leukemia gene correlates with hematopoietic differentiation and is associated with outcome of acute myeloid leukemia. 757 12

The acute promyelocytic leukemia (APL)-specific t(15;17) chromosome abnormality is characterized at the molecular level by rearrangement of the PML and RAR alpha genes, resulting in fusion PML/RAR alpha mRNA and a chimeric protein. Besides its relevance in the pathogenesis of the disease, this hybrid gene represents a specific tumor marker that is rapidly detectable by reverse transcriptase-polymerase chain reaction (RT-PCR) in the RNA extracted from leukemic blasts. Several studies have highlighted the clinical relevance of PML/RAR alpha detection, which provides a specific diagnosis, prognostic information, and prediction of relapse when monitoring residual disease during the follow-up. In fact, this hybrid gene is detected in 100% of APLs. Rare cases of patients with a morphological diagnosis of FAB M3 AML who lack the specific PML/RAR alpha abnormality have been reported as being unresponsive to differentiation treatment. Finally, all the studies reported so far on PCR monitoring in APL have documented that the identification of small amounts of residual disease at remission strongly predicts impending relapse. Thus, RT-PCR of the hybrid PML/RAR alpha gene is currently performed prospectively as part of cooperative clinical trials aimed at better addressing post-remission treatment in APL.
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PMID:The PML/RAR alpha fusion gene in the diagnosis and monitoring of acute promyelocytic leukemia. 762 53

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

The cyclin-dependent kinase 4 (cdk4) inhibitor (p16INK4/MTS1/CDKN2) gene has been recently identified as a putative tumor suppressor gene because of the high frequency of homozygous deletion observed in numerous human tumor cell lines, including leukemias. However, results obtained from uncultured tumor samples have led to discussion of the relevance of these findings. Using reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis, we have investigated p16INK4A gene at both RNA and genomic levels in various types of leukemias: acute myeloid leukemia (AML) (n = 23); acute lymphocytic leukemia (ALL) (n = 22) and B cell chronic lymphoproliferative disorders (CLPD) (n = 33). p16INK4A mRNA expression was not found in only 1/20 AML and 2/23 CLPD samples. Conversely, p16INK4A mRNA was not detected in 5/17 ALL cases, and intensity of PCR products were barely detectable in seven additional cases, possibly related to the contamination by normal cells in some cases. By Southern blotting, a homozygous deletion of p16INK4A gene was found in 6/17 ALL cases (35%) among which 4/6 were negative or weakly positive by RT-PCR assay. None of the five AML and 20 CLL samples studied had p16INK4A deletion. Sequence analysis of p16INK4A exon 2 did not show point mutation in two of these cases lacking mRNA expression. Our data provide further evidence that among hematological malignancies, ALL are the most likely to be associated with p16INK4A inactivation, mainly by homozygous gene deletion. Since most hematological malignancies-except ALL-are infrequently associated with p16INK4A and retinoblastoma (Rb) gene alteration it seems worthwhile to explore cdk4 and cdk6 expression to determine whether or not the disruption of the p16INK4A/Rb/cdk4/cdk6 regulatory loop might play a role in their pathogenesis.
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PMID:Alterations of cyclin-dependent kinase 4 inhibitor (p16INK4A/MTS1) gene structure and expression in acute lymphoblastic leukemias. 763 Jan 99

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)
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PMID:[WT 1 and leukemia]. 764 50

Acute promyelocytic leukaemia (APL) is characterized by t(15;17), which results in the formation of two chimaeric genes, PML-RAR alpha and RAR alpha-PML. PML-RAR alpha transcripts have been detected in all cases of APL whilst those of RAR alpha-PML have been detected in only about 67% of cases. We have used reverse transcriptase polymerase chain reaction (RT-PCR) to detect both fusion transcripts serially in 18 patients in remission of APL after chemotherapy and bone marrow transplantation. All patients were negative for PML-RAR alpha, whereas in six patients (remission 3-9 years) RAR alpha-PML was consistently detected. Only one patient at remission showed the 5' breakpoint RAR alpha-PML, with the rest showing the 3' breakpoint 144 bp RAR alpha-PML. The level of sensitivity for detecting RAR alpha-PML was some 10-fold higher than that for PML-RAR alpha. Serial negative tests for PML-RAR alpha have been correlated with durable remissions, suggesting possible eradication of residual leukaemia in APL. Our results, however, show persistence of t(15;17) cells expressing RAR alpha-PML fusion mRNA in patients in long-term remission of APL. They indicate that patients considered clinically 'cured' of APL still have molecular evidence of minimal residual disease and also provide further insight into the biology of acute myeloid leukaemia.
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PMID:Persistence of RAR alpha-PML fusion mRNA detected by reverse transcriptase polymerase chain reaction in patients in long-term remission of acute promyelocytic leukaemia. 764 2


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