Distribution of BCR::ABL1 Transcripts in the Different Clinical Phases of Chronic Myeloid Leukemia: Effect on Hematological Parameters and Patient Survival

Abstract

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the presence of the Philadelphia chromosome, a product of the reciprocal translocation t(9;22)(q34;q11), in the BCR and ABL genes. These rearrangements in both genes lead to the formation of various fusion mRNA products, with preferential expression of b2a2, b3a2, and other BCR::ABL1 mRNA variants, combined with additional chromosomal abnormalities. Notably, the distribution and frequency of different mRNA variants vary in different populations. However, studies concerning this in Mexico are limited, and the results have been inconclusive. This study therefore aimed to determine the distribution of BCR::ABL1 mRNA variants in different clinical phases of CML and their effect on hematological parameters and patient survival. This study included 33 patients, whose demographic, clinical, and molecular data on BCR::ABL1 mRNA variants and hematological parameters were collected to identify potential associations. A total of 84.8% (n = 28) of patients had BCR::ABL1 translocation and increased platelet and basophil counts. The most frequent mRNA variant was b3a2 (64.3%), followed by b2a2 (28.6%) and e1a2 (3.6%). Concerning the clinical phases of CML, 75.8% (n = 25), 21.2% (n = 7), and 3% (n = 1) of patients were in the chronic, blast, and accelerated phases, respectively. Moreover, the b3a2 mRNA variant was more commonly identified in patients in the chronic phase. No correlation was observed between mRNA variant expression and patient survival. However, b2a2 was indicative of patients with longer survival as well as those treated with imatinib or nilotinib. Additionally, platelet count could be a marker of BCR::ABL1 translocation.

Keywords: Philadelphia chromosome; b2a2; b3a2; chronic myeloid leukemia; e1a2; survival.

Figure 1

Kaplan–Meier survival curves. (a) Survival analysis based on the initial treatment (imatinib or hydroxyurea); no significant differences were found in patient survival probability (p = 0.3253). (b) Survival analysis based on the final treatment (imatinib/nilotinib or others); no significant differences found between the two treatments (p = 0.9296). (c) Survival analysis based on the presence of the BCR::ABL1 translocation; no significant differences (p = 0.64) found between the two groups. (d) Survival probability of patients expressing b2a2 or b3a2 mRNA variants; no significant differences (p = 0.4031) found between the two groups. I/N = treatment with imatinib or nilotinib; Other = treatment with hydroxyurea, hydroxycarbamide, and allopurinol.