Characterisation of clonal Philadelphia-negative cytogenetic abnormalities in a large cohort of chronic myeloid leukaemia

Background: Clonal Philadelphia (Ph)-negative cytogenetic abnormalities (CPCA) have been reported in chronic myeloid leukaemia (CML) patients treated with either interferon or tyrosine kinase inhibitor (TKI). However, the incidences and types of these cytogenetic abnormalities after treatment vary due to the limited populations enroled. Methods: We analysed the frequency and types of CPCA in a cohort of 607 CML patients in the chronic phase after TKI treatment. We also followed up these CPCA with a median of 31.8 months (range from 11 to 63 months) from diagnosis and investigated their effects on disease progression. Results: We found 18 out of 607 CML patients had cytogenetic abnormality in the Ph-negative cells with an incidence of 3%. In total, six types of chromosomal abnormalities have been identified in these 18 patients with the majority of them aneuploidy abnormalities, especially the trisomy 8. Four of 18 patients (22.2%) were noted to have several abnormalities in the Ph-negative cells. Furthermore, follow-up studies of these CPCA showed that they could be either persistent or transient (15 vs 3 patients), and may not affect disease progression since none of them developed transformed myelodysplasia or transformed acute myeloid leukaemia. Conclusion: Three percent of CML patients in the chronic phase were observed to have CPCA during TKI treatment. Our results suggest that the detection of CPCA in CML may not predict disease progression.