Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Rund, D. et al.

Rund, Krichevsky, Bar-Cohen, Goldschmidt, Kedmi, Malik, Gural, Shafran-Tikva, Ben-Neriah, Ben-Yehuda,

Therapy-related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients.

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.[1]

References

Therapy-related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients. Rund, D., Krichevsky, S., Bar-Cohen, S., Goldschmidt, N., Kedmi, M., Malik, E., Gural, A., Shafran-Tikva, S., Ben-Neriah, S., Ben-Yehuda, D. Leukemia (2005) [Pubmed]

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