Clonal chromosomal abnormalities in CD34+/CD38− hematopoietic cells from cytogenetically normal chronic myeloid leukemia patients with a complete cytogenetic response to tyrosine kinase inhibitors

Abstract

Letter to the Editor Clonal chromosomal abnormalities in Ph-negative cells (CCA/Ph-) have been identified in 3-15% of chronic myeloid leukemia (CML) patients with a partial or complete cytogenetic response (CCyR) to imatinib(1). Trisomy 8 and deletions of chromosome 7 [either monosomy 7 or del 7(q)] account for the majority of cases, although a range of other karyotypic changes were seen at lower frequency. A recent study reported CCA/Ph- in patients on dasatinib, indicating that the phenomenon is not limited to imatinib therapy. In some patients, CCA/Ph is associated with a myelodysplastic syndrome (MDS), and progression to acute myeloid leukemia has been reported(1, 2). A single center report suggested inferior survival in newly diagnosed patients who develop CCA/Ph-(3). However, a larger study found that CCA/Ph- does not adversely affect the prognosis of patients with a major cytogenetic response (MCyR) to imatinib, indicating that this is a mostly benign condition(4). The reported incidence of CCA/Ph- is based on metaphase karyotyping, which is limited by the small number of cells analyzed and by the fact that only cells are assayed that can be induced to divide within the culture period. We thus hypothesized that conventional karyotyoping may underestimate the incidence of CCA/Ph- and decided to screen CD34+/CD38− cells from a cohort of CML patients with a CCyR to tyrosine kinase inhibitor (TKI) therapy for abnormalities of chromosomes 7 and 8. This primitive cell compartment is known to be enriched for hematopoietic progenitor and stem cells(5). We find CCA/Ph- in CD34+/CD38− cells from 4/19 patients, suggesting CCA/Ph- is more common than previously appreciated.