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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.

Chronic myelogenous leukemia is the main diagnosis in case of primitive hyperleucocytosis ou thrombocytosis. The Philadelphia chromosome could be evidenced in the bone marrow by cytogenetic analysis or in the peripheral blood by amplification of the BCR-ABL fusion gene with RT-PCR. A new targeted therapy, imatinib mesylate (Gleevec), inhibits of the dysregulated kinase activity of BCR-ABL. A complete cytogenetic response defined by the absence of Ph+ chromosome in bone marrow is obtained in 85% of cases at the daily dosage of 400 mg. The response is then monitored by quantification of the BCR-ABL transcript. This apparent simple, orally available and well tolerated therapy need to be carefully monitored by real time quantitative PCR in highly specialized laboratories. Allogenic hematopoietic stem cell transplantation remains a curative approach in case of HLA identical donor and is proposed to young patients or in case of imatinib failure. A second generation of BCR-ABL inhibitors is currently in clinical trial.