Therapy-related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients
Autor: | A Gural, Dina Ben-Yehuda, N Goldschmidt, S Krichevsky, D Rund, S Ben-Neriah, S Shafran-Tikva, M Kedmi, S Bar-Cohen, E Malik |
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Rok vydání: | 2005 |
Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Pathology Time Factors MLH1 Polymerase Chain Reaction Ribosomal Protein S6 Kinases 90-kDa Cytochrome P-450 Enzyme System Risk Factors hemic and lymphatic diseases Internal medicine Antineoplastic Combined Chemotherapy Protocols Genotype medicine Genetic predisposition Cytochrome P-450 CYP3A Humans Genetic Predisposition to Disease neoplasms Adaptor Proteins Signal Transducing Retrospective Studies Leukemia Hematology business.industry Cytogenetics Nuclear Proteins Microsatellite instability Neoplasms Second Primary Middle Aged Prognosis medicine.disease Immunohistochemistry Survival Analysis Neoplasm Proteins MSH2 Karyotyping Myelodysplastic Syndromes Female Genes MDR Carrier Proteins MutL Protein Homolog 1 business Microsatellite Repeats |
Zdroj: | Leukemia. 19:1919-1928 |
ISSN: | 1476-5551 0887-6924 |
Popis: | Therapy-related leukemia or myelodysplasia (t-leuk/MDS) is a serious problem that is increasing in frequency. We studied the clinical characteristics of 96 patients (pts) with a mean age of 48 years, and analyzed the molecular parameters that could predispose to t-leuk/MDS. Hematological malignancies were the most common primary (53%), followed by breast and ovarian cancer (30% combined). The mean latency until the development of t-AML was 45.5 months. Median survival was 10 months. Cytogenetics was abnormal in 89% of pts. FLT3 internal tandem duplications were found in six of 41 (14.6%) pts, of whom four had an abnormal karyotype. Analysis of drug metabolism and disposition genes showed a protective effect of the CYP3A4 1*B genotype against the development of t-leuk/MDS, whereas the CC genotype of MDR1 C3435T and the NAD(P)H:quinone oxidoreductase1 codon 187 polymorphism were both noncontributory. Microsatellite instability (MSI) analysis using fluoresceinated PCR with ABI sequence analyzer demonstrated that 41% of pts had high levels of MSI in four or more of 10 microsatellite loci. Immunohistochemistry demonstrated reduced expression of MSH2 and MLH1 in 6/10 pts with MSI as compared to 0/5 of pts without MSI. In conclusion, genetic predisposition as well as epigenetic events contribute to the etiology of t-AML/MDS. |
Databáze: | OpenAIRE |
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