Subgroup of patients with Philadelphia-positive chronic myelogenous leukemia characterized by a deletion of 9q proximal to ABL gene

Identification of genes involved in imatinib resistance in CML: a gene-expression profiling approach

“…It is located in the 9q33 region, 15 Mb from the abl1 locus. Large deletions in the derivative chromosome 9, consisting of many megabases, have been associated with poor prognosis, resistance to IFN 28 and to imatinib, 29 although the treatment with imatinib has been described as overcoming the adverse prognostic significance of der(9) deletions. 30 In our series of cases, CgRs were uniformly lower in patients with der(9) deletions.…”

Secondary imatinib resistance associated with an aberrant bcr-abl fusion gene

“…5 Although the patient attained complete cytogenetic remission rapidly and his molecular response was not different from many other patients receiving imatinib, 6 he suddenly developed blast crisis. Deletion of the derivative chromosome 9q has been reported to confer a bad prognosis in patients treated with interferon-alpha 7 and this probably also holds true for imatinib treated patients as was recently shown. 8 However, we can speculate on mechanisms, by which the kringle domain influenced Bcr-Abl function or the activity of imatinib.…”

Derivative chromosome 9 deletions are a significant feature of childhood Philadelphia chromosome positive acute lymphoblastic leukaemia

“…29 The frequency of deletions from the der(9) in CML has been estimated to be 10-15% from a number of studies. 6,[9][10][11][12]30 The incidence reported for ALL is more variable. In our study, the figure of 11% for confirmed deletions is similar to that reported for adult ALL by Specchia et al 13 and Kolomietz et al 11 A lower incidence of 1.5% was reported by Reid et al 14 in their predominantly adult series, while no cases were detected in the series investigated by Lee et al 31 This variation may be a consequence of the small numbers of patients studied, or of a bias in selection.…”

“…[9][10][11][12]23 The poor outcome has been linked to patients with a visible deletion by FISH. Cases of Ph-positive CML have been reported, which lack expression of the ABL/BCR transcript but have no visible deletions.…”

“…6 The most significant clinical finding was that, in CML, the deletions were associated with a worse prognosis. [9][10][11][12] More recent investigations have shown that these deletions also occur in adult ALL, although no association with outcome has yet been established. 13,14 In the study presented here, a series of 27 BCR/ABL positive, childhood ALL patients were investigated using dual colour dual fusion FISH, with a commercially available probe, to determine the incidence of ABL/BCR deletions.…”