BCR-ABL1 transcript types showed distinct laboratory characteristics in patients with chronic myeloid leukemia

Abstract

ABSTRACT. In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting results, the clinical value of these transcripts remains controversial. The aim of this study was to identify associations of e14a2 and e13a2 transcripts with laboratory variables and also the response to treatment. This study included 203 adult patients with CML treated with Imatinib as first-line drug in a reference hematology center in Northeast Brazil. Clinical and laboratory data were obtained after informed consent. Samples were collected for RNA extraction and analyzed by reverse transcription-polymerase chain reaction (PCR), according to the international protocol BIOMED-1. The LeukemiaNet 2013 criteria were used to establish the molecular response. The frequency distribution of the BCR-ABL1 transcripts was e14a2 (64%), e13a2 (34%), and double positives (2%). The results showed a statistically significant association of the e14a2 transcript type with thrombocytosis (P = 0.0005) and the e13a2 with higher leukocyte count (P = 0.0491). In a subgroup of 44 patients, the molecular response to treatment with Imatinib was assessed by quantitative PCR at 3 months (BCR-ABL1 ≤ 10%), 6 months (BCR-ABL1 ≤ 1%), or 12 months (BCR-ABL1 ≤ 0.1%). Although patients with the transcript e14a2 showed higher frequency of good responses than patients with the transcript e13a2, this difference was not statistically significant. In agreement with published data, our results showed association of the BCR-ABL1 transcript e14a2 with thrombocytosis and the BCR-ABL1 transcript e13a2 with higher leukocytosis in patients with chronic myeloid leukemia.

The impact of BCR‐ABL1 transcript type on tyrosine kinase inhibitor responses and outcomes in patients with chronic myeloid leukemia

“…21 In nearly all the studies, sex did not appear to have an impact on the transcript types, including the European LeukemiaNet (ELN) cohort, which to our knowledge has the largest sample size. 2,[22][23][24][25][26][27][43][44][45][46][47][48] However, a small study consisting of 43 patients from Sudan with CML demonstrated a possible relationship between the e13a2 transcript and male sex, 20 which then was confirmed by other 2 large-scale studies from Italy (559 patients) 28 and India (200 patients) 29 (P 5.03 and P 5.05, respectively). In addition, Lin et al 30 demonstrated that female sex was more frequent among patients coexpressing both the e13a2 and e14a2 transcripts (P<.05), although no significant difference with regard to sex was shown in the e13a2 or e14a2 transcript groups.…”

“…However, in their study, the German investigators demonstrated that patients with the e13a2 transcript had significantly higher baseline median leukocyte counts compared with patients with the e14a2 transcript (88 × 10 9 /L vs 65 × 10 9 /L; P <.001), but no such relationship was shown for hemoglobin levels . A recently published study from Brazil also reported similar findings and patients with the e13a2 transcript had a significantly higher median leukocyte count at the time of diagnosis compared with patients with the e14a2 transcript (147 × 10 9 /L vs 129 × 10 9 /L; P = .049) (Table ) …”

“…Other studies did not find a correlation between age and transcript types. [21][22][23][24][26][27][28][29][43][44][45][46][47] Relationship between transcript types and hematologic parameters and risk scores at diagnosis Structural differences in different p210 proteins (ie, e14a2 and e13a2) may result in different tyrosine kinase activities and thus, theoretically, hematologic parameters among patients with CML with the e13a2 and e14a2 transcript types may differ. With regard to the association between transcript types and platelet counts at the time of diagnosis, the literature search demonstrated some contradictory results.…”

“…With regard to the association between transcript types and platelet counts at the time of diagnosis, the literature search demonstrated some contradictory results. In some studies, significantly higher platelet counts were found in patients with the e14a2 transcript compared with those with the e13a2 transcript, 2,21,44,[46][47][48][50][51][52] whereas others demonstrated no difference (Table 2). 2,[21][22][23][24][25][27][28][29][30][43][44][45][46][47]49,53,54 In addition, in the study by Jain et al, 21 significantly higher platelet levels were observed in the patients coexpressing the transcripts compared with patients with the e13a2 transcript alone.…”

“…Bennour et al found that patients with the e14a2 transcript type were significantly older than patients in the e13a2 group (mean age of 56 years vs 26 years; P = .001). Other studies did not find a correlation between age and transcript types …”