Frequency of rare <i><scp>BCR</scp>‐<scp>ABL</scp>1</i> fusion transcripts in chronic myeloid leukemia patients

Aggarwal, Arun Kumar; Senthamizhselvi, A.; Mani, Sathya; Vinodhini, K.; Janet, Nancy Beryl; Lakshmi, Kavitha M; Abraham, Ajay; George, Biju; Srivastava, Alok; Srivastava, Vivi M.; Mathews, Vikram; Balasubramanian, Poonkuzhali

doi:10.1111/ijlh.12616

Cited by 32 publications

(26 citation statements)

References 35 publications

(47 reference statements)

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“…A vast majority of CML patients have the typical e13a2 and/or e14a2 BCR‐ABL1 junction. Several studies with large sample sizes have shown that the frequency of the common e13a2/e14a2 transcript in CML was 97·7% to 98·5% (Ito et al , ; Goh et al , ; Todoric‐Zivanovic et al , ; Arun et al , ), consistent with our findings (98·3%). The e1a2, e19a2 and e13a3/e14a3 transcripts were the most commonly reported types in previous studies (Goh et al , ; Arun et al , ) and the present study.…”

Section: Discussionsupporting

confidence: 91%

“…Several studies with large sample sizes have shown that the frequency of the common e13a2/e14a2 transcript in CML was 97·7% to 98·5% (Ito et al , ; Goh et al , ; Todoric‐Zivanovic et al , ; Arun et al , ), consistent with our findings (98·3%). The e1a2, e19a2 and e13a3/e14a3 transcripts were the most commonly reported types in previous studies (Goh et al , ; Arun et al , ) and the present study. In addition to these 3 types of transcripts, we identified e1a3, e6a2, e8a2, e12a2 and unusual e13a2/e14a2 and found that the three most frequent types accounted for three‐quarters of the cases with uncommon BCR‐ABL1 transcripts.…”

Section: Discussionsupporting

confidence: 91%

“…Regular monitoring of BCR‐ABL1 transcript levels by real‐time quantitative PCR (RQ‐PCR) has become an integral part of routine clinical management of CML in the tyrosine kinase inhibitor (TKI) era (Hughes et al , ); therefore, identifying the junction characteristics of the BCR‐ABL1 fusion gene is necessary for performing appropriate RQ‐PCR. Due to the fairly low incidence and high diversity of uncommon BCR‐ABL1 fusion transcripts, thus far, only a limited number of cohort studies have reported the types and prevalence of uncommon BCR‐ABL1 transcripts in CML patients (Ito et al , ; Goh et al , ; Pardanani et al , ; Verma et al , ; Todoric‐Zivanovic et al , ; Gui et al , ; Arun et al , ). Currently, many studies have revealed outstanding outcomes in CML patients with typical BCR‐ABL1 transcripts (O'Brien et al , ; Baccarani et al , ), and a few studies have reported relatively poor response to TKIs and dismal prognosis in patients with p190 BCR‐ABL1 (Pardanani et al , ; Verma et al , ; Arun et al , ).…”

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confidence: 99%

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Prevalence and outcomes of uncommon BCR‐ABL1 fusion transcripts in patients with chronic myeloid leukaemia: data from a single centre

Qin

Jiang

et al. 2018

Br J Haematol

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To explore the type, prevalence and outcomes in chronic myeloid leukaemia (CML) patients with uncommon BCR-ABL1 transcripts in the era of tyrosine kinase inhibitors (TKIs), uncommon BCR-ABL1 transcripts were screened in 4750 patients by multiplex polymerase chain reaction (PCR), and type-specific real-time quantitative PCR was regularly performed for molecular monitoring. A total of 19 uncommon transcripts, including e1a2, e1a3, e6a2, e8a2, e12a2, unusual e13a2, e13a3, unusual e14a2, e14a3 and e19a2 were identified in 83 (1·7%) patients. The three most frequent types were e19a2, e13a3/e14a3 and e1a2. Compared with the 571 newly diagnosed CML patients in chronic phase with common e13a2/e14a2 transcripts receiving frontline imatinib therapy, patients with the e19a2 (n = 16) and e1a2 (n = 11) transcripts had significantly reduced probabilities of 1-year complete cytogenetic response (CCyR, P = 0·0004 and 0·016) and major molecular response (MMR, P = 0·0018 and 0·0035), and patients with the e13a3/e14a3 transcript (n = 10) had significantly increased probabilities of 1-year CCyR (P = 0·0072) and MMR (P = 0·0073). Patients with the e19a2 transcript had low probabilities of 2-year event-free survival (EFS, P = 0·0004) and progression-free survival (P = 0·0067), and patients with the e1a2 transcript had low probability of 2-year EFS (P < 0·0001). Therefore, uncommon BCR-ABL1 fusion transcripts are rare and diverse in patients with CML and may be relevant for TKI therapy outcomes.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

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confidence: 99%

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Prevalence and outcomes of uncommon BCR‐ABL1 fusion transcripts in patients with chronic myeloid leukaemia: data from a single centre

Qin

Jiang

et al. 2018

Br J Haematol

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“…The incidence rates of the BCR‐ABL1 transcript types gathered from the full‐text articles are given in Table . Of 26 articles, 22 (85%) showed a higher incidence of the e14a2 transcript whereas only 4 articles demonstrated a higher incidence of the e13a2 transcript.…”

Section: Introductionmentioning

confidence: 99%

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

Erçalışkan

Eşkazan

2018

Cancer

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Although the majority of patients with chronic myeloid leukemia do well with treatment with tyrosine kinase inhibitors (TKIs), some patients still have inferior outcomes. There are many factors that might play a part, including the different BCR-ABL1 transcript types at baseline. The current study was performed to determine the possible impact of different transcripts on the treatment responses and outcomes of patients with chronic myeloid leukemia who are receiving TKI therapy. The authors performed a systematic literature search by using the terms "b2a2/b3a2," "e13a2/e14a2," or "transcript type." e14a2 was the more common transcript type. The majority of the studies demonstrated no significant difference regarding age, sex, leukocyte counts, and hemoglobin levels between patients with the e13a2 and e14a2 transcripts. However, in approximately one-half of the studies, the e14a2 transcript was associated with higher platelet counts. Almost no studies demonstrated a significant association between disease risk scores and transcript types. In the majority of studies, having the e14a2 transcript was associated with earlier, deeper, and higher molecular response rates. Although better event-free survival was observed in patients with the e14a2 transcript in some of the studies, the majority demonstrated that transcript type did not have an impact on progression-free and overall survival. Treatment-free remission currently is a topic of much interest, and to the authors' knowledge there are limited data with conflicting results regarding the possible effects of transcript types on the outcomes of patients after discontinuation of TKIs. Because having the e14a2 transcript appears to be related to a favorable outcome, choosing second-generation TKIs for frontline therapy might be a convenient approach in patients with chronic myeloid leukemia with the e13a2 transcript. The authors believe this finding warrants further investigation.

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“…However, the conclusions of these studies are limited by the low number of patients. 5, 8, 9 To investigate the significance of the e1a2 transcript subtype, we examined a cohort of 2322 CML patients treated with tyrosine kinase inhibitors (TKIs), and analyzed the frequency, risk of blastic transformation, treatment response and outcomes of patients with this transcript subtype.…”

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confidence: 99%

Clinical and prognostic significance of e1a2 BCR-ABL1 transcript subtype in chronic myeloid leukemia

et al. 2017

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Frequency of rare BCR‐ABL1 fusion transcripts in chronic myeloid leukemia patients

Cited by 32 publications

References 35 publications

Prevalence and outcomes of uncommon BCR‐ABL1 fusion transcripts in patients with chronic myeloid leukaemia: data from a single centre

Prevalence and outcomes of uncommon BCR‐ABL1 fusion transcripts in patients with chronic myeloid leukaemia: data from a single centre

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

Clinical and prognostic significance of e1a2 BCR-ABL1 transcript subtype in chronic myeloid leukemia

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