Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined clinical, morphologic, and cytogenetic features and ALL-1 (MLL, Htrxl, HRX) gene rearrangements in 17 cases of secondary leukemia that occurred 11 months to 9 years from diagnoses of primary cancers in children who received topoisomerase II inhibitors or developed secondary leukemias typical of those associated with this therapy. Primary diagnoses included nine solid tumors and eight leukemias. Ten secondary leukemias were acute myeloid leukemia (AML), one was of mixed lineage, two were acute lymphoblastic leukemia (ALL), and four presented as myelodysplasia. Of 15 cases with 11q23 involvement, 11 (73%) were cytogenetically identifiable; four cases had molecular rearrangement only. By Southern blot, rearrangements within the ALL-1 gene were similar to sporadic cases. The results of this analysis suggest the following: (1) In most pediatric cases of topoisomerase II inhibitor-associated leukemia, there is disruption of the breakpoint cluster region of the ALL-1 gene at chromosomal band 11q23. (2) Exposure histories vary in secondary 11q23 leukemia, as the only topoisomerase II inhibitor was dactinomycin in one case, and, in another case, no topoisomerase II inhibitor was administered. (3) There is clinical, morphologic, cytogenetic, and molecular heterogeneity in pediatric secondary 11q23 leukemia. (4) There are some survivors of pediatric secondary 11q23 leukemia, but the outcome is most often fatal.
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PMID:ALL-1 gene rearrangements in DNA topoisomerase II inhibitor-related leukemia in children. 775 57

A cytogenetic and/or cytochemical study was performed in 166 individuals with leukemia or related disorders, in two major Costa Rican hospitals. In those patients treated at an adult's hospital (14 years old and over), acute leukemias represented 66% of all cases. In that hospital the most frequent types of disorders were, in decreasing order: ANLL (> M1), ALL, CML (all of them showed the Ph chromosome) and MDS. In the cases from a childrens' hospital (< 14 years old) acute leukemias were 98%. Among them the order of frequency was: ALL (70%): ALL-1 (84%), ALL-2 (16%) and ANLL (27%): M5a > M3 > M4 > M5b. In ALL 85% were type B and occurred mostly in women while 15% of them were type T and more frequent in males. There was 5.6% infant leukemia, which presented a similar number of acute lymphoids and myeloids. The cytogenetic pattern was similar among Costa Rica and other tropical and temperate countries.
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PMID:[Cytogenetics and cytochemistry of leukemia patients in 2 neotropical hospitals]. 1135 79

Patients with relapsed or refractory lymphoma often require treatment with aggressive chemotherapy. At McGill University, a combination of high dose VP-16 and cyclophosphamide (VP-CY) is commonly used as a salvage regimen. In recent years, cytogenetic abnormalities of the long arm of chromosome 11 at band 23 (11q23) have been linked to the use of VP-16, and may be associated with secondary myelodysplastic syndrome or acute leukemia. Therapy related 11q23 anomalies have not been widely studied in lymphoma patients. We have identified and reviewed the course of 107 patients who have been treated with VP-CY. Thirty-five patients remain alive and 21 consented to participate in our study. Patient bone marrows were studied morphologically, cytogenetically and molecularly, to identify any new changes that may have developed over the course of their treatment, with a special emphasis on the search for 11q23 rearrangements. Mean time between VP-CY treatment and marrow evaluation was 3.6 years. Of the 21 patients, 5 had Hodgkin's disease (HD) and 16 had non Hodgkin's lymphoma (NHL). They received a total of 30 cycles of VP-CY. Response rate was 100%, with 16 complete and 5 partial responses. Eighteen patients later underwent autologous stem cell transplantation. At the time of study, 19 of the patients were disease free and 2 were in relapse. On morphological analysis, 12 marrows appeared normal and 6 showed mild dyserythropoiesis. Standard cytogenetics was done to examine for any new chromosomal translocations or deletions. All cytogenetic studies yielded normal results. Molecular analysis by Southern blot was done on 15 patients in a search for 11q23 rearrangements, including the partial tandem duplication of ALL-1. All molecular studies were normal. We conclude that the use of VP-CY, given in our treatment schedule, does not appear to be associated with an increased risk of developing 11q23 rearrangements.
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PMID:Evaluation for the development of 11q23 rearrangements in lymphoma patients treated with a high dose VP-16 and cyclophosphamide salvage regimen. 1285 2