Downregulated expression of genes mapping on chromosome 9 in chronic myeloid leukemia cases bearing genomic deletions on der(9)

Abstract

regimen, with survival of 16 versus 27% respectively, hazard ratio 1.33 (95% CI 1.01-1.77; P ¼ 0.05). 8 When interpreted in the context of our meta-analysis results, the trial results questions the role of fludarabine, cytarabine and priming G-CSF in patients with high-risk AML.There are several limitations to this meta-analysis. First, the 95% CI for all survival outcomes other than remission rates does not exclude the possibility of clinically meaningful effects. However, given the point estimate of a 1% absolute risk difference in overall survival, it is unclear whether CSF priming would warrant prioritization for future study in AML trials, as a definitive trial would likely require several thousand patients. Second, the number of studies did not permit meta-regression or further stratified analyses. In addition, there was substantial heterogeneity in the types of chemotherapy administered concurrent with CSF priming. However, on balance, we did not find clinically important differences in the effect of CSF priming for the variables we examined.In conclusion, the results of this meta-analysis demonstrate that CSF priming does not improve outcome in AML and thus should not be used in routine clinical care. Although this meta-analysis did not definitively address the question of CSF priming in standard risk patients, the overall results of the analysis do not lend strong support to study this question further.

Identification of copy number alterations by array comparative genomic hybridization in patients with late chronic or accelerated phase chronic myeloid leukemia treated with imatinib mesylate

“…Patients started on IM at early chronic phase, however, do not show an adverse association with this deletion [20,21]. The extent of copy number loss on der(9) is variable and may range from a few hundred kilobases to many megabases, and sometimes involving the entire short arm of chromosome 9 [22,23]. We localized the smallest overlapping region of imbalance among the five patients with 9q34 loss to a 1 Mb region proximal to ABL1.…”

“…ASB6 copy loss was, however, uniformly noted among all 5 patients with der(9) loss. The role of ASB6 gene loss and expression down-regulation in conferring poor response to interferon therapy may need further exploration as its gene product contains a C-terminal SOCS box motif that may act as a bridge between specific substrate-binding domains and ubiquitin protein ligases, thus facilitating ubiquitin-mediated degradation and regulation of signaling pathways [23,25].…”