Frequency of BCR-ABL Fusion Transcripts in Iranian Azeri Turkish patients with Chronic Myeloid Leukemia (original) (raw)
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Frequency of BCR-ABL Fusion Transcripts in Iranian Patients with Chronic Myeloid Leukemia
Archives of Iranian Medicine, 2008
Background: A specific chromosomal abnormality, the Philadelphia chromosome, is present in 90 -95% of patients with chronic myeloid leukemia. The aberration results from a reciprocal translocation of chromosomes 9 and 22, creating a BCR-ABL fusion gene. There are two major forms of the BCR-ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcript b2a2 or b3a2 codes for a p210 protein. Other fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Other less common fusion genes are b3a3 or b2a3 (p203) and e19a2 (p230). The incidence of one or other rearrangement in chronic myeloid leukemia patients varies in different reports. In general, fusion transcripts are determined individually, a process which is labor-intensive in order to detect all major fusion transcripts. The objective of this study was to set up a multiplex RT-PCR assay for detection and to determine the frequency of different fusion genes in 75 Iranian patients with chronic myeloid leukemia.
Caspian Journal of Internal Medicine, 2018
Background: A specific chromosomal abnormality, the Philadelphia chromosome (BCR-ABL fusion), is present in all patients with chronic myeloid leukemia (CML). The b2a2 and b3a2 fusion mRNAs encode p210 fusion protein p210 and e1a2 encode p190. The aim of this study was to evaluate the frequency of BCR-ABL fusion transcript variants in Northeast of Iranian CML patients and to compare the laboratory results of our patients. Methods: This study was conducted in 85 peripheral blood and bone marrow samples of CML patients. Ribonucleic acid (RNA) was extracted by a commercial kit, RT-PCR for identifying BCR-ABL fusions was carried out by using designed primers and the PCR products were electrophoresed in agarose gels. Finally, statistical analysis was performed for variant frequency identification and their comparison was performed. Results: All patients examined were positive for BCR/ABL rearrangement. Fusion of b3a2 was detected in 53 (62.35%) patients, b2a2 in 25 (29.41), e1a2 in 1 (1.17%) and coexpression of b3a2 and e1a2 in 6 (7.05%) patients. There were significant differences between the mean age in patients with b3a2 positive (44.07 years) and in b3a2 negative group (50.35 years) however, no significant differences were seen between sex and b2a2 (P=0.61), b3a2 (P=0.79) and e1a2 (P=0.20). Conclusions: This study showed higher frequency b3a2 than b2a2 and e1a2 transcripts in CML patients in Northeast Iran and there was no association between e1a2 transcripts frequencies and monocytosis in peripheral blood.
Frequency of BCR-ABL fusion transcripts in Serbian patients with chronic myeloid leukemia
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
The aim of this study was to analyze the occurrence of the most frequent BCR-ABL transcript variants (b3a2, b2a2 and e1a2) in Serbian patients with chronic myeloid leukemia (CML) and compare it with the occurrence reported in other populations. We analyzed peripheral blood and bone marrow samples of 136 Serbian patients with CML by RT-PCR and cytogenetic methods. In 100 patients (73.5%) the b3a2 and in 34 (25%) the b2a2 forms of BCR-ABL were detected. One (0.75%) patient was BCR-ABL negative, but in lymphoblastic transformation he expressed the e1a2 [corrected] transcript of BCR-ABL. One (0.75%) patient displayed both b2a2 and b3a2 forms of BCR-ABL. Analysis of this group according to karyotype showed b3a2 predominance (79%) in patients with classic t(9;22); b2a2 was found in 20% and both b2a2 and b3a2 forms in 1%. In variant translocations b3a2 in 65% and b2a2 in 35% of the patients were detected. In contrast, the subgroup with normal karyotype expressed slight predominance of the ...
Zahedan Journal of Research in Medical Sciences, 2017
Background: Different BCR-ABL fusion transcripts occur more or less frequently, in three different types of leukemia Objectives: This study was done to determine the frequencies of BCR-ABL fusion transcripts in leukemia patients from Iran. Methods: This experimental study was carried out from 2001 to 2015 in Pasteur Institute of Iran. The leukemia patients containing 348 chronic myeloid leukemia (CML), 72 acute lymphoblastic leukemia (ALL), and 34 acute myeloid leukemia (AML) were studied. Total RNA was extracted from peripheral blood samples and analyzed by multiplex RT-PCR in 486 leukemia patients to detect different types of BCR-ABL transcripts. Fisher's exact test was used in comparing qualitative variables in the case control study. Associations with a P value < 0.05 were considered significant. Results: The BCR-ABL transcript frequencies for CML, ALL and AML patients were 92.0%, 12.5% and 14.7% respectively for all transcripts. The majority of CML patients with positive BCR-ABL expressed one of the p210 BCR-ABL transcripts (86.6%) while the remaining showed other transcripts (p190 BCR-ABL 25 (7.8%)) and p230 BCR-ABL 2 (0.6%)). The rate of co-expression of the p190/p210 transcripts were 16 (5%). In other types of leukemia patients the rates of expression of those transcripts were different. Conclusions: For the first time, we reported co-expression of p210/p190 which may be caused by alternative splicing in Iranian patients. This study we showed no significant correlation between BCR-ABL1 variants, age, sex type, and WBC count of studied leukemia patients.
Frequencies of BCR-ABL1 fusion transcripts among Sudanese chronic myeloid leukaemia patients
Genetics and Molecular Biology, 2010
The incidence of one or other rearrangement in chronic myeloid leukemia (CML) patients varies in different reported series. In this study we report the frequencies of BCR-ABL1 fusion transcript variants studied in 43 CML patients from Sudan. The study includes 46 Sudanese patients, three of which negative for the BCR-ABL1 fusion transcript. More than half of 43 positive patients showed b2a2 fusion transcript (53.5%), while (41.9%) showed b3a2 transcript and the remaining (4.6%) coexpression of b3a2/ b2a2 and b3a2/b2a2/e19a2. We detected neither coexpression of p210/p190 nor e1a2 alone. Male patients showed a tendency to express b2a2, while female tende to express b3a2 (p = 0.017). Moreover, a single nucleotide polymorphism was detected in BCR exon 13 in one out of four patients and this patient showed only b2a2 expression. In conclusion, we observed a significant correlation between sex and type of BCR-ABL1 transcript, an observation that deserves further investigation.
Asian Pacific journal of cancer prevention : APJCP, 2015
Chronic myeloid leukemia (CML) is a myeloproliferative disorder of pluripotent stem cells, caused by reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11), known as the Philadelphia chromosome. A total of 51 CML patients were recruited in this study. Complete blood counts of all CML patients were performed to find out their total leukocytes, hemoglobin and platelets. FISH was performed for the detection of BCR-ABL fusion and cryptogenic tests using bone marrow samples were performed for the conformation of Ph (9;22)(q34;q11) and variant translocation mechanisms. In cytogenetic analysis we observed that out of 51 CML patients 40 (88.9%) were Ph positive and 4 (8.88%) had Ph negative chromosomes. Mean values of WBC 134.5 103/μl, hemoglobin 10.44 mg/dl, and platelets 288.6 103/μl were observed in this study. In this study, Ph positive translocation between chromosome (9:22)(q34;q11) were observed in 40 (88.9%) CML patients.
Blood, 1996
A novel variant of the chimeric BCR-ABL mRNA transcript was detected in a patient with Philadelphia chromosome-negative (Ph-) chronic myelogenous leukemia (CML) by multiplex reverse-transcription polymerase chain reaction (RT-PCR). Sequence analysis of the fusion region of the amplified cDNA fragment showed an in-frame joining of exon e6 of the BCR gene and exon a2 of the ABL gene, giving rise to an e6a2 BCR-ABL transcript. This finding was confirmed by Southern blot analysis using a specific probe corresponding to intron 6 of the BCR gene, whereas conventional Southern blot for rearrangement of the major breakpoint cluster region (M-bcr) was negative. Western blot studies detected a BCR-ABL protein slightly larger than p185 BCR-ABL. Metaphase fluorescence in situ hybridization showed an insertion of ABL material into the BCR region without reciprocal BCR translocation. The findings in this case show that atypical BCR-ABL transcripts are detectable even in Ph- CML patients without M...
Frequency of BCR-ABL 1 Fusion Transcripts Variants in Chronic Myeloid Leukemia Algerian patients
Journal de la faculté de médecine d'Oran, 2017
Objectif-Dans le contexte de la leucémie myéloïde chronique (LMC), la recherche du transcrit de fusion BCR-ABL1 est devenue indispensable pour confirmer le diagnostic moléculaire. Dans cette étude, nous décrivons les différents types de transcrits de fusion BCR-ABL1 retrouvés chez des patients de l'Ouest algérien atteints de leucémie muéloïde chronique (LMC). Méthodes-Au total 167 patients suspects de LMC ont été inclus dans cette étude. La recherche qualitative des transcrits de fusion a été réalisée au service de biochimie de l'Etablissement hospitalier et universitaire d'Oran, par la technique d'amplification en chaine par polymérase après rétro-transcription (RT-PCR). Résultats-Les deux types de transcrits de fusion BCR-ABL1de type majeur Mb3a2 et Mb2a2 étaient présents respectivement dans 59,8 et 36.4 % des cas. Deux patients (1,8%) avaient un transcrit atypique rare de type e19a2 et deux autres (1,8%), ont co-exprimé les deux types b3a2 et b2a2. Conclusion-Notre étude a confirmé les données de la littérature en montrant une incidence plus élevée du transcrit majeur.
BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML
Clinical and Laboratory Haematology, 2002
There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a p210 protein. Another fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Another, less common fusion gene is c3a2[e19a2], which encodes a p230 protein. The incidence of one or the other rearrangement in chronic myeloid leukaemia (CML) patients varies in different reported series. This study was designed to determine the frequency of coexpresion of the p210, p190 and p230 transcripts in 250 Mexican patients with CML. We performed nested and multiplex reverse transcriptase polymerase chain reaction (RT-PCR) on bone marrow samples from adult patients and found that all cases were positive for some type of BCR/ABL rearrangement. In 226 (90.4%) patients it was p210, while the remaining 9.6% showed coexpression or one of the transcripts of p190/p210/p230. In 7% of patients with p210 expression there are both isoforms (b3a2/b2a2), presumably the result of alternative splicing. The rate of coexpression of the p190/p210 transcripts was 5%, which is much lower than in other reports. This may be due to the technical factors. These patients had high platelet counts, marked splenomegaly and chromosomal abnormalities in addition to Ph¢. Other types of coexpression seen were p210/p230 and p190/p210/p230, in patients with high-risk clinical factors. Our study confirms the occurrence of coexpression of different BCR/ABL transcripts, although the rate (9.6%) was much lower than has been reported in other populations. This may reflect either the sensitivity of the detection techniques used or the possibility of genetic differences between the populations studied. Coexpression may be due to alternative splicing or to phenotypic variation, with clinical courses different from classical CML.
Asian Pacific Journal of Cancer Prevention, 2016
Background: Acute lymphoblastic leukemia (ALL) is a heterogeneous disease which requires a risk-stratified approach for appropriate treatment. Specific chromosomal translocations within leukemic blasts are important prognostic factors that allow identification of relevant subgroups. In this study, we developed a multiplex RT-PCR assay for detection of the 4 most frequent translocations in ALL (BCR-ABL, TEL-AML1, MLL-AF4, and E2A-PBX1). Materials and Methods: A total of 214 diagnosed ALL samples from both adult and pediatric ALL and 14 cases of CML patients (154 bone marrow and 74 peripheral blood samples) were assessed for specific chromosomal translocations by cytogenetic and multiplex RT-PCR assays. Results: The results showed that 46 cases of ALL and CML (20.2%) contained the fusion transcripts. Within the positive ALL patients, the most prevalent cryptic translocation observed was mBCR-ABL (p190) at 8.41%. In addition, other genetic rearrangements detected by the multiplex PCR were 4.21% TEL-AML1 and 2.34% E2A-PBX1, whereas MLL-AF4 exhibited negative results in all tested samples. Moreover, MBCR-ABL was detected in all 14 CML samples. In 16 samples of normal karyotype ALL (n=9), ALL with no cytogentic result (n=4) and CML with no Philadelphia chromosome (n=3), fusion transcripts were detected. Conclusions: Multiplex RT-PCR provides a rapid, simple and highly sensitive method to detect fusion transcripts for prognostic and risk stratification of ALL and CML patients.