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- Title
Therapy-related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients.
- Authors
Rund, D.; Krichevsky, S.; Bar-Cohen, S.; Goldschmidt, N.; Kedmi, M.; Malik, E.; Gural, A.; Shafran-Tikva, S.; Ben-Neriah, S.; Ben-Yehuda, D.
- Abstract
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.
- Subjects
LEUKEMIA; HEMATOLOGY; BREAST cancer; OVARIAN cancer; CYTOGENETICS; KARYOTYPES; DRUG metabolism; OXIDOREDUCTASES; ANTINEOPLASTIC agents; CARRIER proteins; COMPARATIVE studies; DISEASE susceptibility; DNA; GENES; HEMOPROTEINS; IMMUNOHISTOCHEMISTRY; RESEARCH methodology; MEDICAL cooperation; MYELODYSPLASTIC syndromes; POLYMERASE chain reaction; PROGNOSIS; PROTEINS; RESEARCH; SURVIVAL analysis (Biometry); TIME; TRANSFERASES; EVALUATION research; RETROSPECTIVE studies; NUCLEAR proteins; SECONDARY primary cancer
- Publication
Leukemia (08876924), 2005, Vol 19, Issue 11, p1919
- ISSN
0887-6924
- Publication type
journal article
- DOI
10.1038/sj.leu.2403947