Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors Journal Article
| Authors: | Megonigal, M. D.; Cheung, N. K. V.; Rappaport, E. F.; Nowell, P. C.; Wilson, R. B.; Jones, D. H.; Addya, K.; Leonard, D. G. B.; Kushner, B. H.; Williams, T. M.; Lange, B. J.; Felix, C. A. |
| Article Title: | Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors |
| Abstract: | Leukemias with MLL gene translocations are a complication of primary cancer treatment with DNA topoisomerase II inhibitors. How early translocations appear during primary cancer treatment has not been investigated. We tracked the leukemic clone with an MLL gene translocation during neuroblastoma therapy in a child who developed acute myeloid leukemia. The karyotype of the leukemic clone showed del(11)(q23). We used panhandle PCR-based methods to isolate the breakpoint junction involving MLL and an unknown partner gene. Marrow DNA from neuroblastoma diagnosis and DNA and RNA from serial preleukemic marrows were examined for the translocation. The karyotypic del(11)(q23) was a cryptic t(11;17). GAS7, a growth arrest- specific gene at chromosome band 17p13, was the partner gene of MLL. Two different MLL-GAS7 fusion transcripts were expressed. The translocation was already detectable by 1.5 months after the start of neuroblastoma treatment. The translocation was not detectable in the marrow at neuroblastoma diagnosis or in peripheral blood lymphocyte DNAs of six normal subjects. GAS7 is a new partner gene of MLL in treatment-related acute myeloid leukemia. MLL gene translocations can be present early during anticancer treatment at low cumulative doses of DNA topoisomerase II inhibitors. Although MLL has many partner genes and most have not been characterized, panhandle PCR strategies afford new means for detecting MLL gene translocations early during therapy when the partner gene is unknown. |
| Keywords: | adolescent; cancer chemotherapy; acute granulocytic leukemia; human cell; dna-binding proteins; exons; case report; cisplatin; doxorubicin; polymerase chain reaction; bone marrow; etoposide; antineoplastic combined chemotherapy protocols; granulocyte macrophage colony stimulating factor; nerve tissue proteins; cyclophosphamide; vincristine; time factors; transcription factors; monoclonal antibody; molecular sequence data; neuroblastoma; ganglioside gd2; nucleotide sequence; leukemia, myeloid; base sequence; translocation, genetic; dna topoisomerase inhibitor; fatal outcome; karyotype; chromosomes, human, pair 11; dna determination; dna topoisomerases, type ii; nephroblastoma; rna analysis; proto-oncogenes; myeloid-lymphoid leukemia protein; chromosome translocation 11; cucurbita; blotting, southern; humans; human; male; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 97 |
| Issue: | 6 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2000-03-14 |
| Start Page: | 2814 |
| End Page: | 2819 |
| Language: | English |
| DOI: | 10.1073/pnas.050397097 |
| PUBMED: | 10706619 |
| PROVIDER: | scopus |
| PMCID: | PMC16012 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work