Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amplification or duplication of the AML1 gene at chromosome band 21q22 was detected by FISH using a locus-specific probe in three out of 171 unselected patients with therapy-related myelodysplasia (t-MDS) or t-AML (1.7%). In two patients AML1 signals were located tandemly on derivative chromosomes, in one patient on a dic(9;21) and in the the other patient on a derivative chromosome 18 made up of interchanging layers of material from chromosomes 9, 14, 18, and 21. In the third patient three single supernumerary copies of AML1 were located on derivatives of chromosomes 19 and 21. All three patients were older, had previously received therapy with alkylating agents without topoisomerase II inhibitors, had complex karyotypes including abnormalities of chromosomes 5 or 7, and presented acquired point mutations of the TP53 gene. No point mutations of the AML1 gene were observed. The results support a pivotal role of impaired TP53 function in the development of gene amplification or duplication in t-MDS and t-AML.
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PMID:Amplification or duplication of chromosome band 21q22 with multiple copies of the AML1 gene and mutation of the TP53 gene in therapy-related MDS and AML. 1561 58

The incidence of therapy-related acute promyelocytic leukemia (t-APL) is apparently rising. We systematically reviewed the English literature until March 15, 2013, and collected a total of 326 t-APL cases, with the following results: (1) t-APL affects predominantly middle-aged adults with a median age at diagnosis of 47 years and a female-to-male ratio of 1.7:1; (2) after an incidence peak at 2 years following the completion of treatment for the primary antecedent disease, the risk of developing t-APL quickly diminishes with time; (3) the four most common primary antecedent conditions are breast cancer, hematological malignancies, multiple sclerosis, and genitourinary malignancies; (4) topoisomerase II inhibitors and radiation represent the most common potential risk factors; (5) despite different DNA damage "hot spot" sites, t-APL has no significant clinicopathologic differences from de novo APL (dn-APL); (6) t(15;17) is the sole cytogenetic abnormality in the vast majority of patients; (7) only a small minority of cases have a myelodysplastic or pancytopenic preleukemic phase; (8) more than one-third of patients come to medical attention incidentally (i.e., due to laboratory abnormalities), while the most common symptom is mucocutaneous bleeding, and 79 % have clinical DIC; and (9) the remission rate of t-APL is about 80 %, similar to dn-APL.
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PMID:Therapy-related acute promyelocytic leukemia: a systematic review. 2377 99