Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm (MPN) caused by the abnormal proliferation of granulocytes from a pluripotent stem cell. In Amazonas, it is the 5th most common cancer in men and the 6th in women, accounting for 15% of cases. CML is characterized by the presence of the Philadelphia chromosome (Ph+), resulting from the translocation of chromosomes 9 and 22, forming the BCR::ABL1 oncogene. Variants of the BCR::ABL1 gene are related to increased resistance to drug therapies, such as Imatinib, thus interfering with the treatment response of CML patients and leading to a poorer prognosis.

To evaluate the presence of variants in the BCR::ABL1 gene in samples from patients undergoing treatment for CML.

Molecular assays for variant detection by Sanger genetic sequencing were performed on samples from patients with elevated BCR::ABL1 transcript levels after 3 months of treatment with a tyrosine kinase inhibitor.

Of the 16 samples analyzed, 13 were men (81.25%) and 3 were women (18.75%), with a mean age of 48.2 years and a mean BCR::ABL1 transcript level of 65.87% (IS). Additionally, the treatment resistance rate was 75% in these patients. Sanger sequencing analysis was performed from exons 4 to 9 of the ABL1 gene. Of the 16 samples, 6 showed a variant in BCR::ABL1, all with the same missense variant V256E. This variant was described only in silico (CancerVar) as pathogenic. Of the patients positive for the V256E variant, 4 were men (83.33%) and 2 were women (16.6%), with a mean age of 45.6 years. These patients had a mean BCR::ABL1 transcript level of 30.56% (IS), considered elevated (European LeukemiaNet), which conferred treatment resistance in 83.33% of cases.

In CML, studies associate the presence of variants in the BCR::ABL1 gene with a lower response to treatment and poorer clinical outcomes. In this study, among the patients who presented the V256E variant, more than 80% underwent a change in therapy to Nilotinib or Dasatinib due to intolerance and/or resistance to Imatinib. Additionally, these patients did not show a molecular response, with the BCR::ABL1 transcript remaining unchanged or elevated.

This study provided the first report of the V256E variant in CML patients from Amazonas. The detection of variants in the BCR::ABL1 gene offers new perspectives for the management of CML patients, as the presence of variants is associated with treatment failure. Thus, this study aims, through the detection of variants, to assist in a more assertive and individualized approach for CML patients in the State of Amazonas.