Are the Secondary Chromosome Abnormalities Seen in Chronic Myeloid Leukemia (CML) Cells Induced to Ph-Chromosome Negativity by Imatinib a Result of Chromosome Instability or a Side Effect of the Therapy - a Study in GIST (Gastrointestinal Stromal Cell Tumors) Patients Treated With Imatinib.
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the
presence of the Philadelphia (Ph) chromosome - a t(9:22) translocation that results in the
production of a BCR/ABL fusion protein with Abl kinase activity.
Imatinib mesylate (Gleevec) specifically targets a limited set of protein tyrosine kinases -
ABL, Arg (Abl-related gene), c-Kit, platelet-derived growth factor receptor (PDGF-R) - and
their oncogenic forms, most notably BCR/ABL Imatinib is also a potent inhibitor of a
receptor-type c-Kit tyrosine kinase. Therefore imatinib was examined for therapeutic
efficacy against malignant gastro-intestinal stromal tumors (GIST) Recent articles have
drawn attention to the development of new Ph-negative, cytogenetically unrelated clones
after therapy of Ph-positive CML with imatinib. Trisomy 8 and monosomy 7 are the most
frequent defects, but other aberrations have also been reported. Some of these cytogenetic
abnormalities are associated with acute myeloid leukemia and MDS.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
~ presence or absence of genetic abnormality as seen in CML patients on imatinib
Jeff Lipton, MD
University Health Network, DMOH
Canada: Health Canada