Abstract
We investigated genetically affected leukemic cells in FIP1L1-PDGFRA+ chronic eosinophilic leukemia (CEL) and in BCR-ABL1+ chronic myeloid leukemia (CML), two myeloproliferative disorders responsive to imatinib. Fluorescence in situ hybridization specific for BCR-ABL1 and for FIP1L1-PDGFRA was combined with cytomorphology or with lineage-restricted monoclonal antibodies and applied in CML and CEL, respectively. In CEL the amount of FIP1L1-PDGFRA+ cells among CD34+ and CD133+ cells, B and T lymphocytes, and megakaryocytes were within normal ranges. Positivity was found in eosinophils, granulo-monocytes and varying percentages of erythrocytes. In vitro assays with imatinib showed reduced survival of peripheral blood mononuclear cells but no reduction in colony-forming unit growth medium (CFU-GM) growth. In CML the BCR-ABL1 fusion gene was detected in CD34+/CD133+ cells, granulo-monocytes, eosinophils, erythrocytes, megakaryocytes and B-lymphocytes. Growth of both peripheral blood mononuclear cells and CFU-GM was inhibited by imatinib. This study provided evidence for marked differences in the leukemic masses which are targeted by imatinib in CEL or CML, as harboring FIP1L1-PDGFRA or BCR-ABL1.
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Acknowledgements
We thank Dr F Falzetti and Dr T Zei for selection of CD34+ cells; Dr G Guglielmini and Dr A Santucci for preparation of histograms, and Dr GA Boyd for assistance in the preparation of this paper. This study was supported by grants from AIRC (Associazione Italiana Ricerca sul Cancro), Associazione ‘Sergio Luciani’; Fabriano, Italy, Fondazione Cassa di Risparmio, Perugia, Italy, MIUR (Ministero per l’Istruzione, l’Università e la Ricerca Scientifica), the Belgian Programme of Interuniversity Poles of Attraction initiated by Belgian State, Prime Minister's Office, Science Policy Programming and the Leukemia Reasearch Fund, UK. PV is a Senior Clinical Investigator of FWO-Vlaanderen. BC is supported by FIRC (Federazione Italiana Ricerca sul Cancro).
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Crescenzi, B., Chase, A., Starza, R. et al. FIP1L1-PDGFRA in chronic eosinophilic leukemia and BCR-ABL1 in chronic myeloid leukemia affect different leukemic cells. Leukemia 21, 397–402 (2007). https://doi.org/10.1038/sj.leu.2404510
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DOI: https://doi.org/10.1038/sj.leu.2404510