Frequency of Bcr-Abl Fusion Oncogene Splice Variants Associated with Chronic Myeloid Leukemia (CML)

Iqbal, Zafar; Manzoor, Fatima; Iqbal, Mudassar; Ali, Shahid; Sheikh, Nadeem; Khan, Mubbsher Munawar; Aleem, Aamer; Akhtar, Tanveer

doi:10.4236/jct.2011.22022

Cited by 6 publications

(8 citation statements)

References 18 publications

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“…A study conducted in India and Bulgaria calculated the ratio of the two major transcripts of M-BCR region e14a2:e13a2 to be 1.3:1, which is almost in agreement to the ratio observed in the present study [ 13 , 24 ]. However, studies from our local population represent comparatively higher ratio of the two transcripts than reported here [ 9 , 25 ]. Two times higher (ratio 2:1) of e14a2 than e13a2 were also reported in CML patients in Brazil, Malaysia, and Korea [ 26 , 27 , 28 ], while studies from Iran and India demonstrated the frequency of e14a2 transcripts to be almost three times higher than that of e13a2 [ 29 , 30 ].…”

Section: Discussioncontrasting

confidence: 57%

“…The classic transcript found in majority of CML patients is b2a2 or b3a2, formed by fusing exon 13 (b2) or exon 14 (b3) of BCR to exon 2 (a2) of ABL gene, respectively. Both of them code for a 210 kDa (p210) novel protein [ 9 ]. More than 95% of BCR – ABL transcripts are either e13a2 or e14a2 in CML.…”

Section: Introductionmentioning

confidence: 99%

“…Reverse transcriptase PCR (RT-PCR) is one of the most sensitive techniques used for detection of BCR–ABL transcripts associated with CML [ 9 ]. Most of the current RT-PCR methods are designed and optimized for detecting the transcript of M-BCR and m-BCR breakpoints.…”

Section: Introductionmentioning

confidence: 99%

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Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia

Amin

Ahmed²

2021

Open Medicine

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Background Depending on breakpoints of rearrangement different types of BCR–ABL fusion protein can be generated in patients of chronic myeloid leukemia (CML). The aim of this study is to observe frequencies of major transcripts in CML patients by reverse transcriptase polymerase chain reaction (RT-PCR) and their hematological features at the time of presentation. Materials and methods This cross sectional study was performed at Molecular Lab of Riphah International University, Islamabad from January to June 2019. Consecutive peripheral blood samples of 70 newly diagnosed CML patients in chronic phase were analyzed by RT-PCR to detect different BCR–ABL transcripts. Routine blood cell counts were assessed by an automated hematology analyzer. Results All samples expressed typical BCR–ABL rearrangement. Expression of either e14a2 or e13a2 transcript was detected in 38 (54%) and 30 (43%) patients, respectively. Coexpression of e13a2 + e14a2 was found in 2 (3%) patients. The mean total leukocyte count was higher in group expressing e13a2 (P = 0.01). Higher mean platelet count was noted in patients with e14a2 transcript, but this difference was statistically insignificant (P = 0.1). The association of male gender was observed with the group exhibiting e14a2 (P = 0.01). There was no statistically significant association between transcript type and different ranges of age, hemoglobin levels, and platelet and total leukocyte counts (P > 0.05). Conclusion e14a2 transcript was most common transcript in CML patients. Patients exhibiting e13a2 subgroup presented with significantly higher mean white blood cell count at the time of presentation. Significantly higher proportion of male patients was found to express e14a2 transcript over e13a2.

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Section: Discussioncontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

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Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia

Amin

Ahmed²

2021

Open Medicine

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“…This disagreement may be due to the difference in the duration of nilotinib treatment among patients and differences in sample size and ethnic group may also relevant, since the frequencies of different fusion oncogenes associated with leukemia can vary in different ethnic groups [26].…”

Section: Discussionmentioning

confidence: 99%

Effects of nilotinib on platelet function in patients with chronic myeloid leukemia in chronic phase

Alqasim

Obaid

Yaseen

et al. 2019

Leukemia Research Reports

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Background Tyrosine kinases are highly expressed in platelets and play an important role in their activation process. Some studies have reported the blocking effects of tyrosine kinase inhibitors on different platelet functions. Objectives Evaluate the effects of nilotinib on platelets aggregation in 42 patients with chronic phase of CML and correlate the results with clinical and hematological parameters: age, complete blood count and presentation. Patients and methods This study was conducted on 42 patients diagnosed as Chronic Phase of Chronic Myeloid Leukemia based on clinical, morphological and cytogenetic study. All patients were on Nilotinib treatment and were attending the National Center of Hematology in Baghdad. About 9 mL of venous blood sample were collected from each patient and control subjects, samples divided into 3 parts for complete blood count, platelet aggregation test and PT and aPTT. Results The mean age was 41.3 ± 1.7 (mean ± SEM) years old. M:F ratio of 1.2:1. Mean duration of nilotinib therapy(1.4 years). All patients had normal PT and aPTT. Only 16 (38%) patients had abnormal aggregation response to epinephrine, but there was no statistically significant differences with control group. Conclusion Nilotinib had no adverse effect on platelet function nor patients clotting tests.

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“…In other Asian countries, the distribution was also similar to our findings. [ 14 15 ] In all the aforementioned studies, the ratio was roughly calculated to be b3a2:b2a2 = 60:40. However, the role of BCR-ABL transcripts variants in the prognosis had always been a controversial issue.…”

Section: Discussionmentioning

confidence: 99%

Incidence of BCR-ABL transcript variants in patients with chronic myeloid leukemia: Their correlation with presenting features, risk scores and response to treatment with imatinib mesylate

Deb¹,

Chakrabarti²,

Chakrabarty³

et al. 2014

Indian J Med Paediatr Oncol

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Context:The exact role of the different transcript variants of BCR-ABL in the pathogenesis of chronic myeloid leukemia (CML) and their impact on prognosis is yet to be definitely enumerated.Aims:In this study, we have tried to correlate the presenting features, risk scores and treatment response with the BCR-ABL variants detected in our patients.Settings and Design:A cross-sectional unicentric hospital-based study on 80 patients diagnosed to have CML by bone marrow cytogenetics and confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR).Materials and Methods:RT-PCR for BCR-ABL was performed on consecutive patients with CML attending the CML clinic from January 2010 to December 2010. The medical charts of these patients were analyzed after a follow-up of 18 months in a retrospective manner.Statistical Analysis:Box plot and histogram was used to see the distribution of variables. t-test was performed to enumerate the difference between risk scores in two populations of patients carrying two different BCR-ABL transcript variants.Results:Nearly 56.25% of patients had b3a2 (e14a2) while 41.25% of patients showed b2a2 (e13a2) transcripts. The rest 2.5% (two patients) expressed the rare e19b2 variant. Patients with b2a2 presented with higher Sokal, Hasford and European Treatment and Outcomes Study score than their b3a2 counterpart. Different parameters such as the platelet count, leukocyte count, hemoglobin and splenomegaly showed a minor difference between the groups. More patients in the b2a2 group achieved complete hematologic response at 3 months, but it was not significant.Conclusions:Patients with b2a2 variant CML tend to present with higher risk score, but do not behave in a vastly different manner than their b3a2 counterparts.

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Frequency of Bcr-Abl Fusion Oncogene Splice Variants Associated with Chronic Myeloid Leukemia (CML)

Abstract: BCR-ABL fusion oncogene originates from the reciprocal translocation of chromosome

Cited by 6 publications

References 18 publications

Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia

Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia

Effects of nilotinib on platelet function in patients with chronic myeloid leukemia in chronic phase

Incidence of BCR-ABL transcript variants in patients with chronic myeloid leukemia: Their correlation with presenting features, risk scores and response to treatment with imatinib mesylate

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