TY - JOUR
T1 - Clonal cytogenetic abnormalities in Philadelphia chromosome negative cells in chronic myeloid leukemia patients treated with imatinib
AU - Loriaux, Marc
AU - Deininger, Michael
PY - 2004/11
Y1 - 2004/11
N2 - Treatment of chronic myeloid leukemia (CML) with imatinib (Gleevec®) induces a much higher rate of partial and complete cytogenetic responses (CCR) than interferon-α (IFN)-based therapies. Conventional wisdom suggests that elimination of the Philadelphia (Ph)- positive cells will lead to re-establishment of normal Ph-negative hematopoiesis. Surprisingly, karyotypic abnormalities were detected in the chromosome negative cells of some patients with cytogenetic response to imatinib. In some cases, this was associated with a myelodysplastic syndrome (MDS). While clonal evolution in Ph-positive cells is considered part of the progression of CML, clonal evolution in Ph-negative cells had been observed only rarely in a small number of patients treated with IFN or bone marrow transplantation, raising the question whether the phenomenon may be causally linked to imatinib therapy. In this manuscript, we will review the currently available data, suggest possible causes and discuss potential implications for patient management. We are fully aware that a systematic study of a larger patient cohort will be required to conclusively address these issues.
AB - Treatment of chronic myeloid leukemia (CML) with imatinib (Gleevec®) induces a much higher rate of partial and complete cytogenetic responses (CCR) than interferon-α (IFN)-based therapies. Conventional wisdom suggests that elimination of the Philadelphia (Ph)- positive cells will lead to re-establishment of normal Ph-negative hematopoiesis. Surprisingly, karyotypic abnormalities were detected in the chromosome negative cells of some patients with cytogenetic response to imatinib. In some cases, this was associated with a myelodysplastic syndrome (MDS). While clonal evolution in Ph-positive cells is considered part of the progression of CML, clonal evolution in Ph-negative cells had been observed only rarely in a small number of patients treated with IFN or bone marrow transplantation, raising the question whether the phenomenon may be causally linked to imatinib therapy. In this manuscript, we will review the currently available data, suggest possible causes and discuss potential implications for patient management. We are fully aware that a systematic study of a larger patient cohort will be required to conclusively address these issues.
KW - Chronic myelogenous leukemia
KW - Clonal evolution
KW - Imatinib mesylate
KW - Philadelphia-negative hematopoiesis
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U2 - 10.1080/10428190410001723278
DO - 10.1080/10428190410001723278
M3 - Review article
C2 - 15512807
AN - SCOPUS:8644286697
SN - 1042-8194
VL - 45
SP - 2197
EP - 2203
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 11
ER -