Clinical utility of genomic DNA Q-PCR for the monitoring of a patient with atypical e19a2 BCR-ABL1 transcripts in chronic myeloid leukemia

Atypical BCR-ABL1 transcripts occur in around 3% of patients with chronic phase chronic myeloid leukemia (CML) [1]. Due to the rarity of each individual transcript type there are limited data on the biological and clinical consequences of atypical transcripts. Several reports have suggested an adverse clinical outcome in CML patients with e19a2 BCR-ABL1 treated with ABL1 tyrosine kinase inhibitors (TKIs) [1,2]. One potential contributor to adverse outcome is the lack of standardized molecular monitoring for atypical transcripts. In some cases, this might lead to delayed diagnosis when a screening test for the common e13a2 and e14a2 transcripts is negative. In other cases, the lack of precise response data that can be aligned with molecular response targets on the BCRABL1 International Scale (BCR-ABL1IS) might limit the clinician’s capacity to detect sub-optimal response or impending resistance and alter treatment accordingly. Here we report a case of e19a2 CML with imatinib failure in association with a T315I kinase domain mutation. Asciminib was given as second-line treatment and led to the achievement of a deep molecular response determined by patient-specific genomic DNA PCR. A 62 year old woman presented in July 2015 with morphological features of CML on a blood test performed for occupational screening. She was asymptomatic and physical examination revealed only mild splenomegaly palpable at the costal margin. A screening test for BCR-ABL1 e13a2/e14a2 was negative. A bone marrow biopsy confirmed chronic phase CML with t(9;22)(q34;q11) and long template PCR for BCR-ABL1 using primers that span BCR exon 1 and ABL1 exon 3 amplified e19a2 transcripts [3]. Her ELTS score was low risk.