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Characterization of Ph‐negative abnormal clones emerging during imatinib therapy
Author(s) -
Abruzzese Elisabetta,
Gozzetti Alessandro,
Galimberti Sara,
Trawinska Malgorzata Monika,
Caravita Tommaso,
Siniscalchi Agostina,
Cervetti Giulia,
Mauriello Alessandro,
Coletta Angela Maria,
De Fabritiis Paolo
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22699
Subject(s) - imatinib , myeloid leukemia , medicine , stem cell , imatinib mesylate , clone (java method) , population , philadelphia chromosome , clinical significance , tyrosine kinase inhibitor , cd34 , cancer , cancer research , immunology , pathology , biology , chromosomal translocation , genetics , dna , environmental health , gene
BACKGROUND. Imatinib is a tyrosine kinase‐specific inhibitor widely used for the treatment of chronic myeloid leukemia (CML). Studies reported the occurrence of additional cytogenetic abnormalities in the Philadelphia chromosome (Ph)‐negative cell population emerging after treatment‐induced suppression of the Ph‐positive clone. These abnormalities were described in a relatively high proportion of patients treated with imatinib compared with the anecdotal reports of similar cases in patients treated with other drugs. However, the origin of these abnormalities as well as their biological and clinical significance are unknown. METHODS. The study involved 13 cases of patients diagnosed with CML carrying cytogenetic abnormalities in their Ph‐negative cell population after imatinib treatment. The presence of the markers within the CD34+ stem cell compartment and the cell culture growth were analyzed and patients were followed over time. RESULTS. CD34+ cells express the cytogenetic markers present in Ph− cells, suggesting a possible involvement of the stem cell population. Cultured cells showed normal growth in all but 1 patient. No growth advantage was demonstrated for the Ph‐negative or the Ph‐positive clone after cell culture. CONCLUSIONS. After follow‐up of up to 49 months, none of the patients had evolved to myelodysplasia or acute leukemia. Hypothesis regarding the biological and clinical significance of these abnormalities are formulated. Cancer 2007. © 2007 American Cancer Society.