INTRODUCTION: Chronic myeloid leukemia (CML) is characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL1 gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. CML progresses from a chronic phase (CP) to an accelerated phase (AP), and/or a blast phase (BP) when diagnosed late or untreated. This progression is frequently preceded or accompanied by recurring secondary chromosomal abnormalities which are believed to play a role in the transformation of different phases. In Western countries, the atypical Philadelphia chromosome accounts for less than 5% of CML patients, but they account for 25% of the 101 CML cases in our cohort. Moreover, telomere length shortening is known to be associated with disease progression. The dynamic length changes of individual telomeres might be involved in the remodeling of the genome of the CML cases presenting atypical Philadelphia chromosome. Therefore, it is essential to know the individual telomere length of CML patients presenting atypical translocations.

OBJECTIVE: The goal of this study is to determine the length of telomeres on each chromosomal arm of CML patients presenting atypical Philadelphia chromosome.

METHODOLOGY: We used Cy3 labeled peptide nucleic acid probes specific for (T2AG3)3 sequences as well as centromeric probes as an internal control to perform quantitative fluorescence in situ hybridization (Q-FISH). Following the microscopic acquisition of Q-FISH pictures with Metasystem (Isis), multicolor FISH was performed on the same slide (M-FISH). The Q-FISH helps measure individual telomere length while M-FISH enables characterization of chromosomal translocation.

RESULTS: We report a rare case presenting an atypical Philadelphia chromosome and a pericentric inversion inv(9)(p22q34) involving the derivative chromosome 9 that resulted from t(9;22)(q34;q11.2) in a patient with Ph-positive CML. We found that the chromosome 1 present the highest intensity 98 of telomere while the shortest was the chromosome 22 with 43. The derivative chromosome 9 presenting the inversion has a lowest intensity 99 of telomere, compare to its homologue the normal.

CONCLUSION: We reported here a rare chromosomal abnormality in CML and the dynamic changes of individual telomere length in atypical translocations may be associated with primary and secondary therapeutic resistance in CML.