Clonal Chromosomal Abnormalities in Philadelphia-Negative Cells and Their Clinical Significance in Patients with Chronic Myeloid Leukemia: Results of a Single Center

Abstract

Objective: Chronic myeloid leukaemia (CML) is a haematological disease characterised by the presence of reciprocal t(9;22) translocation, called Philadelphia (Ph) chromosome. Highly improved haematological and cytogenetic results were reported in patients with chronic phase CML after introduction of imatinib into the market. Recently a number of studies draw attention to the emergence of clonal chromosomal abnormalities (CCAs) in Ph (-) cells during cytogenetic follow-up of CML patients. The clinical significance ofthe CCAs has not yet been clearly defined. The present study aims to demonstrate the occurrence pattern of CCA in Ph (-) cells in our cohort of CML patients and to investigate the impact of CCAs on the course and prognosis of CML. Material and Methods: A total of 45 patients were evaluated. Thirty-five patients with clonal chromosomal abnormalities in Ph(-) cells constituted the first group (GI), which was compared to a second group (GII) of 10 patients with complete cytogenetic response but no CCAs in terms of survival and disease progression. Results: The most frequent CCAs were -21, -18 and -20, followed by -22, -10, -17 and -19. Trisomies of Y and 8 were seen in 2 patients. In 9 cases structural abnormalities, such as del(7)(q11), del(17)(q11q21) and different marker chromosomes were observed. There were no difference between the two groups in terms of survival and progression. Dysplasia to some extent seems to occur in both groups irrespective of presence or absence of CCAs. Conclusion: According to our results, there is no convincing evidence that CCAs can alter the natural course of CIVIL on imatinib. We suggest that, regular cytogenetic monitoring with classical cytogenetic analysis is essential for CML patients on tyrosine kinase inhibitors, however it would be advisable to confirm and follow the most frequently observed numerical abnormalities by FISH technique as well.