Comprehensive Molecular Analyses in a Case of Masked Philadelphia Chronic Myeloid Leukemia

Here, we report the case of an 80-year-old woman with masked Philadelphia chronic myeloid leukemia (Ph CML). At diagnosis, qualitative PCR demonstrated the presence of a typical e14a2 configuration, and chromosome analysis showed an apparently normal female karyotype. However, FISH with BCR-ABL1 dual fusion probes gave a positive signal in 152/200 analyzed nuclei, with the fusion signal detected on the long arm of a cytogenetically normal chromosome 9. Using locus-specific probes for chromosome 9 and 22 telomeres, a third chromosome involvement was excluded. Furthermore, microarray analysis from the same specimens showed a normal result. Due to a high Charlson Comorbidity Index, the patient was treated with a reduced dose of imatinib, achieving a rapid hematological response after 1 month. However, after 6 months of imatinib therapy, she had to be considered as warning (Ph+ 26.5%, BCR-ABL1 >1%) according to the European LeukemiaNet 2013 recommendations. In conclusion, we confirmed the importance of a combination of cytogenetic and molecular techniques for the diagnosis and therapy monitoring of masked Ph CML, but, different from what has been reported in the literature so far, we cannot completely exclude the fact that the unusual cytogenetic pattern of this patient may have negatively influenced her response to tyrosine kinase inhibitor therapy.