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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-07-2053.
Submitted July 17, 2002
Accepted October 15, 2002
Emergence of clonal cytogenetic abnormalities in PH-negative cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority
Thomas Bumm, Christel Mueller, Haifa-Kathrin Al-Ali, Knut Krohn, Patricia Shepherd, Erika Schmidt, Sabine Leiblein, Christina Franke, Evelin Hennig, Thomas Friedrich, Reiner Krahl, Dietger Niederwieser, and Michael W Deininger*
Department of Hematology/Oncology, University of Leipzig, Leipzig, Germany
Interdisciplinary Center for Clinical Research, University of Leipzig, Leipzig, Germany
Department of Haematology, Western General Hospital, Edinburgh, United Kingdom
Department of Pathology, University of Leipzig, Leipzig, Germany
BMT/Leukemia Center, Oregon Health and Science University, Portland, OR, USA
* Corresponding author; email: deininge{at}ohsu.edu.
Chronic myelogenous leukemia (CML) is characterized by the presence of a Bcr-Abl fusion protein with de-regulated tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib (STI571), a selective inhibitor of Bcr-Abl, induces major (MCR) or complete cytogenetic remissions (CCR) in the majority of patients with CML in 1st chronic phase. However, thorough re-evaluation of cytogenetics in a cohort of patients in MCR or CCR demonstrated clonal karyotypic abnormalities in more than 10% of cases, some of which were clinically associated with a myelodysplastic syndrome (MDS). Further analysis identified previous exposure to cytarabine and idarubicin as significant risk factors for the subsequent occurrence of abnormalities in Ph-negative cells. In order to investigate if cytogenetically normal but clonal hematopoiesis might be present in other patients in cytogenetic remission, we studied X-chromosome inactivation as a marker of clonality by PCR analysis of the human androgen receptor (HUMARA). We find that imatinib restores a polyclonal pattern in most patients in CCR and MCR. Nonetheless, our results are consistent with the notion that targeted therapy of CML with imatinib favors the manifestation of Ph-negative clonal disorders in some patients. They indicate that patients on imatinib should be followed with conventional cytogenetics, even after induction of CCR.
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Chromosomal abnormalities in Ph- cells of patients on imatinib
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Blood 2003 102: 2700-2701.
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