Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.
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PMID:WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. 794 79

We describe here a 39-year-old male with acute promyelocytic leukemia (APL) carrying a new complex translocation (15;20;17). A chromosomal analysis of the bone marrow cells showed 46, XY, t(15;20;17)(q22;p13;q21). Fluorescence in situ hybridization (FISH) analysis using plasmid DNA libraries of chromosomes 15, 17, and 20 revealed three derivative chromosomes, der(15)t(15;17), der(17)t(17;20), and der(20)t(15;20). Fluorescence in situ hybridization with cosmid DNA probes flanking the breakpoints of t(15;17) did not show the retinoic acid receptor alpha (RAR alpha)/PML fusion signal usually generated on the der(17)t(15;17). However, rearrangement of the RAR alpha gene and expression of the PML/RAR alpha chimeric transcript were identified by Southern blot and reverse-transcriptase polymerase chain reaction (RT-PCR) analyses, respectively. Our results confirmed that the PML/RAR alpha gene on the der(15)t(15;17), not the RAR alpha/PML gene, must be essential to leukemogenesis in APL. Furthermore, considering another reported case with a 20p13 aberration, it is possible that 20p13 is a nonrandom breakpoint in APL with a complex translocation.
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PMID:A new complex translocation (15;20;17)(q22;p13;q21) in acute promyelocytic leukemia. 949 8