[Chronic myeloid leukemia with variant e19a2 BCR-ABL1 fusion transcript: interest of the molecular identification at diagnosis for minimal residual disease follow-up]. / Leucémie myéloïde chronique avec transcrit de fusion variant BCR-ABL1 e19a2 : intérêt de l'identification moléculaire au diagnostic pour le suivi de la maladie résiduelle.

ABSTRACT

We report here the case of a sixty-eight-year old woman with chronic myeloid leukemia. Molecular techniques identified the presence of the rare e19a2 BCR-ABL1 transcript. The patient was treated by 1(st) generation tyrosine-kinase inhibitor (TKI) (imatinib). Disease monitoring was performed by cytogenetic analyses and quantification of the BCR-ABL1 transcript. After 3 months, the treatment was modified due to an absence of biological response and poor tolerance. After 21 months with 2nd generation TKIs (nilotinib), the patient was responding optimally to treatment, with a complete cytogenetic response and a major molecular response. This observation emphasizes the importance of determining the chromosomal breakpoints at diagnosis to enable adequate molecular monitoring of residual disease. Careful monitoring of minimal residual disease is important to thoroughly assess the response to treatment, detect resistance and adapt the therapeutic strategy. The kinetics and the depth of the response to TKI also represent major prognostic factors. Molecular monitoring is performed using real-time quantitative PCR, which has to be adapted to each type of transcript. For rare BCR-ABL1 transcripts, an international standardization, as it is developed for conventional transcripts, is lacking. Yet, such a harmonization would be useful to assess in an optimal and large scale way the response to TKI in these patients, and to determine what the best management is.