Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide

Abstract

In patients with low and intermediate risk myelodysplastic syndrome and deletion 5q (del(5q)) treated with lenalidomide, monitoring of cytogenetic response is mandatory, since patients without cytogenetic response have a significantly increased risk of progression. Therefore, we have reviewed cytogenetic data of 302 patients. Patients were analyzed by karyotyping and fluorescence in situ hybridization. In 85 patients, del(5q) was only detected by karyotyping. In 8 patients undergoing karyotypic evolution, the del(5q) and additional chromosomal aberrations were only detected by karyotyping. In 3 patients, del(5q) was only detected by fluorescence in situ hybridization, but not by karyotyping due to a low number of metaphases. Karyotyping was significantly more sensitive than fluorescence in situ hybridization in detecting the del(5q) clone. In conclusion, to optimize therapy control of myelodysplastic syndrome patients with del(5q) treated with lenalidomide and to identify cytogenetic non-response or progression as early as possible, fluorescence in situ hybridization alone is inadequate for evaluation. Karyotyping must be performed to optimally evaluate response.

Trial registration: ClinicalTrials.gov NCT00179621 NCT01099267.

Figures

Figure 1.

(A) Karyogram of a patient with myelodysplastic syndrome and a deletion in the long arm of chromosome 5 (fluorescence R-banding). (B) More detailed analysis identified the deletion as an interstitial deletion. (C) Comparison with the ideogram of chromosome 5 shows that the breakpoints are located in 5q14 and 5q34. (D) Scheme of fluorescence in situ hybridization to detect a deletion in 5q. The probe localized to the short arm of chromosome 5 (5p21) generates a green control signal. The probe binding to the commonly deleted region 5q31 gives an orange signal. (E) Interphase nucleus with a normal signal constellation, i.e. two green and two orange signals. (F) Interphase nuclei with a signal constellation indicative of a deletion in 5q, i.e. two green signals and one orange signal.