The Negative Prognostic Impact of Derivative 9 Deletions in Patients Who Received Hydroxyurea Treatment for Chronic Myelogenous Leukemia in the Chronic Phase

Abstract

Background: Chronic myeloid leukemia (CML) is characterized by the formation of the BCR/ABL fusion gene, as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. This study was to investigate the incidence and prognostic significance of derivative chromosome 9 (der(9)) deletions in CML patients who received hydroxyurea treatment in the chronic phase. Patients and Methods: Fluorescence in situ hybridization (FISH) analysis was used to assess the der(9) deletion status of 48 CML patients in blast crisis (CMLBC). Results: Among the 48 CML patients, 8 (16.7%) showed der(9) deletions, and the deletions were also existent at diagnosis. The median duration of the chronic phase for patients with der(9) deletions was 18 (range 4–38) months compared to 48 (range 0–204) months for patients without deletions (p < 0.001). Der(9) deletions were not associated with increased karyotypic instability. There was no difference in the probability of the der(9) deletions between the cases having progressed to myeloid or lymphoid blast crisis. Conclusion: The results indicated that the FISH technique could effectively detect der(9) deletions. CML patients with der(9) deletions show more rapid progression and poorer prognosis, and the deletion status is a powerful prognostic factor.

Detection of derivative 9 deletion by BCR-ABL fluorescence in-situ hybridization signal pattern to evaluate treatment response in CML patients

“…Therefore ours and others findings suggest that interpretation of results should be made in light with conventional cytogenetic and FISH (10). Similarly, deletion of ABL-BCR (OGY) on derivative 9 was seen in 11.1% of PT which was comparable with reported 15%-20% cases in CML (13)(14)(15). While deletion in ABL, BCR or complex three way translocation (OGGY, OOGY, OOGGY) was seen in 22.2% of PT which is comparable with 24.4% of patients reported by Lee et al (16).…”

“…While deletion in ABL, BCR or complex three way translocation (OGGY, OOGY, OOGGY) was seen in 22.2% of PT which is comparable with 24.4% of patients reported by Lee et al (16). Deletion of any of the BCR or ABL genes on derivative chromosome 9 was reported to be associated with shorter overall and event free survival resulting into poor prognosis (15,16) . Patients with ABL-BCR deletion represented by OGY variant signal pattern by D-FISH were not different in terms of clinical or laboratory features.…”

Prognostic Factors in Chronic Myeloid Leukemia (CML)

“…However, only large deletions that span the der(9) breakpoint are an adverse risk factor. In the study by Li et al [16] published in this issue of ONKOLO-GIE, FISH analysis was used to assess der(9) deletion status of 48 CML patients in blast crisis. Among the 48 CML patients, 8 (16.7%) showed der(9) deletions, and the deletions had also existed at diagnosis.…”