Analysis of mRNA transcripts in chronic myeloid leukemia patients

Meissner, Rosely de Vasconcellos; Covas, Dimas Tadeu; Dias, Paula Menna Barreto; Job, Fani; Leite, Márcia; Nardi, Nance Beyer

doi:10.1590/s1415-47571999000400003

Cited by 4 publications

(7 citation statements)

References 26 publications

(19 reference statements)

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“…Many studies have evaluated the levels of hemoglobin, leukocytes, basophils, myeloblasts, platelets, spleen size and Sokal score in patients with different transcripts 8, 9, 11, 13, 14, 15. In the present study, eosinophil counts, liver size, Hasford score, EUTOS score, ELTS score and event-free survival were evaluated.…”

Section: Discussionmentioning

confidence: 96%

“…Many studies suggest that hematological and clinical parameters can be influenced by the transcriptional variant type that is expressed 6, 7, 8. Studies in this field have shown controversial results in terms of platelet counts: although most studies have failed to demonstrate any significant correlation, others have demonstrated higher platelet counts in patients with the b3a2 transcript 6, 9, 10, 11…”

Section: Introductionmentioning

confidence: 99%

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Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

Filho

Barbosa

et al. 2019

Hematology, Transfusion and Cell Therapy

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Introduction and objective In this study, we evaluated the influence of the transcript type on hematological and clinical parameters, as well as the event-free survival of 50 patients in the Chronic myeloid leukemia chronic phase. Methods We reviewed the medical records of 55 patients with Chronic myeloid leukemia. The eligibility criteria were based on the availability of hematological and clinical baseline data in the medical records. Data on BCR-ABL transcripts were obtained from medical records. Results Eighteen patients (36%) had the b2a2 transcript, 24 (48%) had b3a2 and 8 (16%) had b2a2/b3a2 . The median platelet count for transcripts b2a2 , b3a2 and b2a2/b3a2 was 320.65 × 10 3 /L, 396 × 10 3 /L, and 327.05 × 10 3 /L, respectively ( p = 0.896). We could not find any differences in relation to the other hematological parameters, when compared to the transcript type. Comparison between spleen and liver size and type of transcript did not differ inside the groups ( p = 0.395 and p = 0.647, respectively) and the association between risk scores and transcript type did not show statistical significance ( p > 0.05). The 21-month probability for event-free survival was 21%, 48% and 66% for the transcripts b2a2 , b3a2 and b2a2/b3a2 respectively ( p = 0.226) Conclusion We conclude that the expression BCR-ABL transcripts have no influence on hematological, clinical and event-free survival parameters of patients in the Chronic myeloid leukemia chronic phase.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

Filho

Barbosa

et al. 2019

Hematology, Transfusion and Cell Therapy

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“…Meissner et al (1999), Cruz et al (2014), andAl-Achkar et al (2016) found no significant association between the transcript type and various clinical and laboratory parameters. However, the e14a2 transcript has been associated with high platelet count (Inokuchi et al, 1991;Perego et al, 2000;Rosas-Cabral et al, 2003;Bennour et al, 2013) and age at diagnosis (Bennour et al, 2013).…”

Section: Discussionmentioning

confidence: 97%

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

Vasconcelos¹,

Azevedo²,

Melo³

et al. 2017

Genet. Mol. Res.

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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.

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“…The e13a2 junction may be more prevalent in men, 20 although not necessarily in all ethnic groups, and has been associated with blast crisis of myeloid phenotype. 7 The e14a2 transcript has been correlated with a higher platelet count in both adults 8,10 and children.…”

Section: Discussionmentioning

confidence: 99%

Chronic myeloid leukemia patients with the e13a2 BCR-ABL fusion transcript have inferior responses to imatinib compared to patients with the e14a2 transcript

Lucas¹,

Harris²,

Giannoudis³

et al. 2009

Haematologica

100

113

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BackgroundChronic myeloid leukemia is characterized by a reciprocal translocation between chromosomes 9 and 22, creating the fusion gene BCR-ABL. The clinical significance of the type of BCR-ABL transcript in newly diagnosed patients in chronic phase treated with imatinib 400 mg from initial diagnosis remains unknown. Design and MethodsWe analyzed the clinical outcome of 78 newly diagnosed chronic phase patients, aged 16 or over, treated with imatinib 400 mg. Of these, 71 expressed either e13a2 or e14a2 transcripts. BCR-ABL transcripts were assayed by quantitative real-time polymerase chain reaction. ResultsAfter 12 months of treatment, 54% of the e14a2 patients had achieved a complete cytogenetic response, compared to 25% of the e13a2 patients (p=0.01). Kaplan-Meier analysis of the time to achieve complete cytogenetic response revealed that e14a2 patients had more rapid response rates, compared to e13a2 patients (p=0.006). e14a2 patients had a higher event-free survival rate in the first 12 months of treatment, although overall survival did not differ significantly between the patients with the two types of transcript. Human organic cation transporter protein 1 mRNA levels did not differ between the patients with the two types of transcript. The pre-treatment pCrKL/CrKL ratio (a surrogate marker of BCR-ABL tyrosine kinase activity) was higher in patients with e13a2 transcripts than in those with e14a2 (p=0.017). ConclusionsPatients expressing the e14a2 transcript type have a higher rate and more rapid complete cytogenetic responses than e13a2-expressing patients, which may be due to higher BCR-ABL tyrosine kinase activity. Knowledge of the transcript type may yield additional prognostic information, although this requires testing on larger datasets.Key words: chronic myeloid leukemia, BCR-ABL fusion transcript, imatinib. Haematologica 2009;94:1362-1367. doi:10.3324/haematol.2009 This is an open-access paper.

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Analysis of mRNA transcripts in chronic myeloid leukemia patients

Cited by 4 publications

References 26 publications

Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

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

Chronic myeloid leukemia patients with the e13a2 BCR-ABL fusion transcript have inferior responses to imatinib compared to patients with the e14a2 transcript

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