Molecular cytogenetic study of derivative chromosome 9 deletion in chronic myeloid leukemia patients

Abstract

The aims of this study are to investigate the frequency of derivative chromosome 9 (der (9)) deletion in Tunisian patients with chronic myeloid leukemia (CML) and to assess the correlation between this deletion and the cytogenetic response for patients treated with hydroxyurea (HU) or imatinib (IM). Karyotype analysis of 336 patients with CML was performed with R-banding technique. Fluorescence in situ hybridization (FISH) was carried using home-brew probes 17L7 and 248J22 for detecting, respectively, adjacent 5'ABL and 3'BCR deletions on der(9). Cytogenetic study demonstrated typical t(9;22)(q34;q11) translocation in 89.6% and variant translocation in 10.4% of patients. Interphase FISH studies showed deletion of der(9) in 59 (17.6%) of the 336 patients, 23 (39%) of them had variant rearrangements. There are 19 patients with solely 5'ABL deletion and 40 with concomitant 5'ABL and 3'BCR deletions. Cytogenetic response was evaluated during 18 months with HU or IM therapy. Our results demonstrate that (a) 3'BCR deletion is associated with 5'ABL deletion in all patients with der(9) deletions, (b) the 5'ABL and 3'BCR deletions arise simultaneously with t(9;22), (c) deletions on der(9) chromosome were frequently encountered in older patients and in patients presenting variant rearrangements, (d) both 5'ABL and 3'BCR deletions were associated with cytogenetic response failure in patients treated with HU, however, patients treated with IM and carrying der(9) deletions presented better cytogenetic response.

Chronic myeloid leukemia: Relevance of cytogenetic and molecular assays

“…In patients presenting deletion, we have defined only a single population of 3 BCR and/or 5 ABL deletions, there was not a combination of cells with and without deletions. Thus, suggests that deletion on der(9) chromosome appears at the same time as the translocation t(9;22) and does not constitute a clonal evolution, signing a progression of the disease as reported in some studies (Bennour et al, 2012b;Xinh et al, 2006). Sinclair et al (Albano et al, 2007) reported that deletion breakpoints are various.…”

Calibration of interphase fluorescence in situ hybridization cutoff by mathematical models

“…The low false positive rate of D‐FISH is achieved by a more complex positive signal pattern, which is characterized by two fusion signals, while there is only one fusion signal in S‐FISH . Nevertheless, Dewald and Vaz reported 9–33% of patients with chronic myeloid leukemia have der(9q) deletion. Deletion of der(9q) leads to the loss of one of two fusion signals in D‐FISH, the same characteristic in S‐FISH with high false positive rate.…”