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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-07-2053.
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Blood, 1 March 2003, Vol. 101, No. 5, pp. 1941-1949
NEOPLASIA
Emergence of clonal cytogenetic abnormalities in Ph
cells in some CML patients in cytogenetic remission to imatinib but
restoration of polyclonal hematopoiesis in the majority
Thomas Bumm,
Christel Müller,
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. N. Deininger
From the Department of Hematology, University of
Leipzig, Germany; Interdisciplinary Center for Clinical
Research, University of Leipzig, Germany; Department of
Haematology, Western General Hospital, Edinburgh, United
Kingdom; Department of Pathology, University of Leipzig,
Germany; and BMT/Leukemia Center, Oregon Health and
Science University (OHSU), Portland, OR.
Chronic myelogenous leukemia (CML) is characterized by the presence
of a Bcr-Abl fusion protein with deregulated
tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib, a selective inhibitor of
Bcr-Abl, induces major cytogenetic remission (MCR) or
complete cytogenetic remission (CCR) in the majority of patients with
CML in first 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 Philadelphia chromosome-negative (Ph ) cells. 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 polymerase chain
reaction 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 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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Blood 2003 102: 2700-2701.
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