Clinical implications of 13q14 and 17p13 deletion, t(4;14) and 1q21 amplification in patients with relapsed multiple myeloma treated by Thalidomide or Bortezomib (Velcade)

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Authors

KUGLÍK Petr ZAORALOVÁ Romana FILKOVÁ Hana GREŠLIKOVÁ Henrieta NĚMEC Pavel OLTOVÁ Alexandra POUR Luděk ADAM Zdeněk KREJČÍ M. HÁJEK Roman

Year of publication 2007
Type Article in Proceedings
Conference Chromosome Research
MU Faculty or unit

Faculty of Medicine

Citation
Field Genetics and molecular biology
Keywords Multiple myeloma; cIg-FISH; 13q deletion; p53 deletion; t(4;14); amp1q21; Velcade; Thalidomide
Description The aim of this study was to investigate if Thalidomide or Bortezomib (Velcade) is able to antagonize the impact of negative cytogenetic prognostic markers in patients with relapsed multiple myeloma (MM). We have focused on four chromosomal aberrations known as negative prognostic factors in MM treated by conventional or myeloablative treatment: deletion of 13q14, deletion of 17p13 (p53), translocation t(4;14) and amplification of CKS1B gene (amp1q21). We have identified monotypic plasma cells and studied chromosomal aberrations by cytoplasmic light-chain fluorescence in situ hybridization (cIg-FISH) technique. Two groups of patients with relapsed multiple myeloma of similar age, sex, stage of the disease and other parameters were treated by Thalidomide based regimens (24 patients) and by Bortezomib based regimens (18 patients). In our preliminary experiments, we did not find statistically significant difference in OS and TTP between patients with/without chromosomal aberrations (del p53, t(4;14), ampl 1q21). So it is possible that the new drugs overcome their negative prognostic impact. Patients with 13q14 deletion had significant shorter time to progression median (8.9 month) in comparison with patients lacking RB deletion. Similarly, patients with combination of 3 or 4 of unfavorable cytogenetic abnormalities had significant shorter time to progression median (6.0 month) in comparison with patients with 1 or 2 aberrations These data suggest that cytogenetic abnomalities can define subgroup of patients with relapsed MM not benefiting from Thalidomide and velcade treatment. Data are still preliminary and we need wait for results from large randomized trials.
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