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Dynamics of cytogenetic aberrations in Philadelphia chromosome positive and negative hematopoiesis during dasatinib therapy of chronic myeloid leukemia patients after imatinib failure

From the III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany (AF, MCM, PE, TL, MG, OF, WS, RH, AH); MLL Münchner Leukämielabor GmbH, München, Germany (CH)

Correspondence: Alice Fabarius, III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Ruprecht-Karls-Universität Heidelberg, Wiesbadener Straße 7–11, 68305 Mannheim, Germany. E-mail: alice.fabarius{at}med3.ma.uniheidelberg.de

Clonal cytogenetic aberrations of the Philadelphia chromosome (Ph) positive hematopoiesis have been associated with the natural evolution of chronic myeloid leukemia (CML) to advanced disease. Clonal aberrations of Ph negative metaphases have been described after treatment with interferon or imatinib. This study evaluates the effect of dasatinib on Ph positive clones with additional cytogenetic aberrations and the frequency of novel aberrations in Ph positive and negative metaphases. Seventy-one patients treated with dasatinib after imatinib failure for a median of nine months were evaluated. Novel aberrations within Ph positive and negative clones appeared in six and three patients, respectively.

Key words: chronic myeloid leukemia, cytogenetics, clonal evolution, tyrosine kinase inhibitors, dasatinib.

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				A. Fabarius, M. Giehl, B. Rebacz, A. Kramer, O. Frank, C. Haferlach, P. Duesberg, R. Hehlmann, W. Seifarth, and A. Hochhaus Centrosome aberrations and G1 phase arrest after in vitro and in vivo treatment with the SRC/ABL inhibitor dasatinib Haematologica, August 1, 2008; 93(8): 1145 - 1154. [Abstract] [Full Text] [PDF]