No significance of derivative chromosome 9 deletion on the clearance kinetics of BCR/ABL fusion transcripts, cytogenetic or molecular response, loss of response, or treatment failure to imatinib mesylate therapy for chronic myeloid leukemia

Abstract

Although deletion of the derivative chromosome 9 (der 9; del-der 9) carries a poor prognosis in patients with chronic myeloid leukemia (CML) who are treated with hydroxyurea or interferon, its significance in patients on imatinib mesylate (IM) therapy is debated. In the current study, the authors used a locus-specific indicator breakpoint cluster region/receptor tyrosine kinase (BCR/ABL) probe to evaluate the significance of del-der 9 in 163 patients with CML who had fluorescence in situ hybridization (FISH) results available. Serial changes in BCR/ABL fusion transcript levels also were monitored by using messenger RNA (mRNA) quantitative polymerase chain reaction (PCR). Of 163 patients, 22 (13.5%) had del-der 9 before commencing IM therapy. No differences were noted in the time to hematologic response (P = .598), major cytogenetic response (CyR) (P = .281), complete CyR (P = .883), major molecular response (MoR) (P = .125), or complete MoR (P = .834). In addition, the times to loss of response (LOR) (P = .974), treatment failure (P = .455; including primary hematologic or cytogenetic resistance and LOR), transformation-free survival (P = .276), and dose escalation of IM (P = .816) did not differ significantly between patients with and without del-der 9. The results of serial BCR/ABL mRNA quantitative PCR revealed similar patterns of BCR/ABL fusion gene reduction between the 2 groups. The presence of del-der 9 in patients with CML did not influence 1) the response to IM therapy in terms of hematologic response, CyR, or MoR; 2) LOR; 3) treatment failure; 4) progression to accelerated phase/blast crisis; or 5) time to dose escalation of IM. Therefore, the authors concluded that the detection of del-der 9 does not have an impact on the current management of patients with CML who are receiving IM therapy.