Imatinib has the ability to inhibit the dysregulated kinase activities of the BCR-ABL fusion protein in CML pts as well as the mutated KIT in GIST patients and has been successfully used to treat both diseases. Several cases of chromosomal abnormalities in Ph-negative metaphases have been reported in CML patients in chronic phase during treatment with imatinib. This is different from true clonal evolution in that the additional cytogenetic abnormalities occur in Ph-negative cells. Although this has also been rarely reported in patients receiving other therapies its frequency in patients on imatinib is relatively high (up to 17% patients) and it may occur when imatinib is given upfront or after other treatment modalities.The most common abnormalities are trisomy 8 and chromosome 7 defects, often associated with myelodysplasia. The time from the beginning of treatment until their appearance is variable, ranging from 3 months to more than a year, with the largest published series reporting a median of 6 months (
Cancer 2003; 98:1905
). The pathogenesis and clinical significance of these findings is still unclear and an important question is whether these clones are induced or favored by the treatment itself, since imatinib is known to have several effects on important growth regulatory proteins involved in hematopoiesis. GIST patients without hematological disease and treated with imatinib offer a unique opportunity to address this question. From Aug 2001 to Aug 2003, 11 patients with GIST were treated with imatinib at our institution and 7 agreed to participate in the sutdy. Their median age was 54-y and they were on imatinib for a median of 18 months (4 to 18) at doses between 400 to 800mg daily. Complete karyotyping on metaphase spreads from peripheral blood and bone marrow aspirates were performed. PB and BM smears were examined for myelodysplastic features. A median of 19 (15 to 24) PB and 16 (13 to 22) BM metaphases were examined for each patient. No abnormal hematological clones were detected and 1 patient had a constitutional variant 46XY, (inv9)(p11;q12) on PB and BM cells. No dysplastic features were observed. These data, although based on a small number of patients suggest that in patients without hematological disease imatinib by itself does not induce hematopoietic clonal cytogenetic abnormalities.
