Emergence of Ph negative clones in chronic myeloid leukemia (CML) patients in complete cytogenetic remission after therapy with imatinib mesylate (STI)

Persistence of chromosomal abnormalities additional to the Philadelphia chromosome after Philadelphia chromosome disappearance during imatinib therapy for chronic myeloid leukemia

“…[1][2][3] In these cases, imatinib treatment induces the disappearance of the Ph + population, allowing the clone marked by the additional abnormality alone to persist. This observation may have important prognostic and pathogenetic implications.…”

Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance

“…In all, 60-80% of CML patients who progress exhibit secondary chromosomal abnormalities in addition to the Ph chromosome. 82 Clonal evolution has been demonstrated to occur during imatinib therapy and to be associated with advanced disease. [82][83][84][85] Recent reports indicate that chromosomal abnormalities are also emerging in Ph-negative cells in CML patients on imatinib therapy.…”

“…82 Clonal evolution has been demonstrated to occur during imatinib therapy and to be associated with advanced disease. [82][83][84][85] Recent reports indicate that chromosomal abnormalities are also emerging in Ph-negative cells in CML patients on imatinib therapy. 24,[85][86][87][88][89][90][91][92][93][94] The underlying mechanism for the appearance of these clones during imatinib treatment is not completely understood.…”

Neoplastic stem cells: A novel therapeutic target in clinical oncology

“…[118][119][120][121][122][123][124][125][126][127][128][129] The introduction of STI571 (imatinib) in BCR/ABL-positive chronic myeloid leukemia (CML) and ALL and all-trans retinoid acid in acute promyelocytic leukemia are 2 important examples. [118][119][120][121][122][123][124][125][126][127][128][129] However, unexpectedly, treatment with imatinib in patients with CML is not associated with the elimination of the entire CML clone, which points to drug resistance in stem cells. It also has been reported that BCR/ABL may exist in different mutant forms in these patients and that, during treatment, imatinib-resistant BCR/ABL mutants are selected and may grow to overt disease.…”