Clinical significance of development of Philadelphia-chromosome negative clones in patients with chronic myeloid leukemia treated with imatinib mesylate.

To The Editor, Since the introduction of imatinib mesylate as treatment for chronic myeloid leukemia (CML) there have been increasing reports of patients developing Philadelphia (Ph) chromosome negative cytogentic clones, a rare phenomenon in the pre-imatinib era. We wish to report our experience of patients who developed Ph negative clones whilst on imatinib therapy, and briefly review the potential clinical implications of this phenomenon. Between 2000 and 2004, a total of 69 patients with CML treated with imatinib had had karyotyping performed at our institution. Of these, 3 (4%) were identified with Ph negative clones on routine cytogenetic analysis. The absence of a silent t(9;22) was confirmed in all 3 cases by interphase FISH analysis utilizing a BCRABL dual fusion probe (Vysis) as well as a probe specific for the identified non-Ph abnormality.