Prognostically Significant Fusion Oncogenes in Pakistani Patients with Adult Acute Lymphoblastic Leukemia and their Association with Disease Biology and Outcome

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TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). This translocation is associated with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug based remission induction phase of treatment as well as overall treatment. Thus, the higher the frequency of this fusion oncogene, the easier to manage childhood ALL in a given region with less intensive chemotherapy. Although global frequency of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found in some geographical regions, including one study from Lahore, Punjab, Pakistan and others from India. The objective of present study was to investigate if this low frequency of TEL-AML1 in pediatric ALL is only in Lahore region or similar situation exists at other representative oncology centers of Pakistan. A total of 167 pediatric ALL patients were recruited from major pediatric oncology centers situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR). Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL-AML1+ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing early remission and good overall survival. Thus, our findings indicate an overall low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with lower representation of this prognostically important genetic abnormality in other less developed countries, specifically in south Asia, thus associating it with poor living standards in these ethnic groups. It also indicates ethnic and geographical differences in the distribution of this prognostically important genetic abnormality among childhood ALL patients, which may have a significant bearing on ALL management strategies in different parts of the world.

Section: Molecular Genetic Studies On 167 Pediatric All Patients Frommentioning

confidence: 98%

Section: Molecular Genetic Studies On 167 Pediatric All Patients Frommentioning

confidence: 99%

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Molecular Genetic Studies on 167 Pediatric ALL Patients from Different Areas of Pakistan Confirm a Low Frequency of the Favorable Prognosis Fusion Oncogene TEL-AML1 (t 12; 21) in Underdeveloped Countries of the Region

Iqbal

2014

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“…However, this method has limited use for identification of certain rearrangements such as t(12;21), ETV6/RUNX1 which requires FISH for detection (Romana et al, 1994;Spathas et al 1999). Hence, chromosomal analysis with FISH is more effective in diagnosing certain cryptic translocations (Nordgren et al, 2002), using RT-PCR and interphase-FISH investigated the frequency of 5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome (Sabir et al, 2012). FISH was used as a complementary method in this study for some ALL patients to reconfirm cytogenetic findings and also those poor quality samples.…”

Section: Introductionmentioning

confidence: 99%

Importance of FISH combined with Morphology, Immunophenotype and Cytogenetic Analysis of Childhood/Adult Acute Lymphoblastic Leukemia in Omani Patients

Goud¹,

Salmani²,

Harasi³

et al. 2015

Genetic changes associated with acute lymphoblastic leukemia (ALL) provide very important diagnostic and prognostic information with a direct impact on patient management. Detection of chromosome abnormalities by conventional cytogenetics combined with fluorescence in situ hybridization (FISH) play a very significant role in assessing risk stratification. Identification of specific chromosome abnormalities has led to the recognition of genetic subgroups based on reciprocal translocations, deletions and modal number in B or T-cell ALL. In the last twelve years 102 newly diagnosed childhood/adult ALL bone marrow samples were analysed for chromosomal abnormalities with conventional G-banding, and FISH (selected cases) using specific probes in our hospital. G-banded karyotype analysis found clonal numerical and/or structural chromosomal aberrations in 74.2% of cases. Patients with pseudodiploidy represented the most frequent group (38.7%) followed by high hyperdiploidy group (12.9%), low hyperdiploidy group (9.7%), hypodiploidy (<46) group (9.7%) and high hypertriploidy group (3.2%). The highest observed numerical chromosomal alteration was high hyperdiploidy (12.9%) with abnormal karyotypes while abnormal 12p (7.5%) was the highest observed structural abnormality followed by t(12;21)(p13.3;q22) resulting in ETV6/RUNX1 fusion (5.4%) and t(9;22)(q34.1;q11.2) resulting in BCR/ABL1 fusion (4.3%). Interestingly, we identified 16 cases with rare and complex structural aberrations. Application of the FISH technique produced major improvements in the sensitivity and accuracy of cytogenetic analysis with ALL patients. In conclusion it confirmed heterogeneity of ALL by identifying various recurrent chromosomal aberrations along with non-specific rearrangements and their association with specific immunophenotypes. This study pool is representative of paediatric/adult ALL patients in Oman.

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Asian Pac J Cancer Prev, 15 (22), 9961-9966

IntroductionThe Philadelphia chromosome (Ph), t (9; 22) (q34; q11.2) is transcribed into a fusion gene, BCR-ABL (Awan et al, 2012;Sabir et al, 2012). This translocation is one of the most common genetic abnormalities detected in leukemia.

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mentioning

confidence: 99%

Clinical Significance of BCR-ABL Fusion Gene Subtypes in Chronic Myelogenous and Acute Lymphoblastic Leukemias

Zhou²,

Zhou³

et al. 2014

Asian Pac J Cancer Prev, 15 (22), 9961-9966 IntroductionThe Philadelphia chromosome (Ph), t (9; 22) (q34; q11.2) is transcribed into a fusion gene, BCR-ABL (Awan et al., 2012;Sabir et al., 2012). This translocation is one of the most common genetic abnormalities detected in leukemia. The site of the breakpoint in the BCR gene may influence the phenotype of diseases. In the vast majority of patients, the breakpoints in the BCR gene are clustered within three well-defined regions: (I) a 55 kb sequence of the first intron, called the minor breakpoint cluster region (m-bcr); (II) a 5.8 kb region spanning exons 12-16, called the major breakpoint cluster region (M-bcr), and finally; (III) intron 19, called μ-bcr. The resultant fusion transcript (e1-a2) (m-bcr) encodes a 190 kDa chimeric protein (p190), and in cases of M-bcr, codes a 210 kDa chimeric protein (p210) and in cases of μ-bcr, a 230 kDa protein (p230) (Fausel, 2007). Large studies indicated that BCR-ABL fusion gene is a highly useful diagnostic tool that controls the effectiveness of the chronic myelogenous