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Clinical Medicine Insights: Oncology

Molecular Cytogenetics in Childhood Acute Lymphoblastic Leukemia: A Hospital-Based Observational Study

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Clinical Medicine Insights: Oncology 2015:9 39-42

Original Research

Published on 24 Mar 2015

DOI: 10.4137/CMO.S24463


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Abstract

Objective: This study was conducted to determine the frequency of chromosomal aberrations in children aged <19 years with newly diagnosed acute lymphoblastic leukemia (ALL), attending/admitted in the Department of Pediatrics and Radiotherapy, Government Medical College, Jammu. Furthermore, we aimed to study the correlation between the cytogenetic molecular abnormalities and the immediate clinical outcome (induction of remission).

Materials and methods: This was a prospective study conducted over a period of 2 years (May 2011 to May 2013) in a tertiary care hospital in India. Forty pediatric (1–19 years) patients (18 males, 22 females; M: F = 0.8 : 1) with newly diagnosed ALL were studied for molecular cytogenetic analysis. Written consent was obtained from the parents of the patients. Bone marrow aspiration was done for making the diagnosis of ALL. Children lost to follow-up and who failed to give consent were excluded from the survey. Host factors and clinical parameters were obtained from patients.

Results: Bone marrow aspirate samples of 40 diagnosed cases of ALL were subjected to routine cytogenetic analysis, and reverse transcription-polymerase chain reaction (RT-PCR) technique was used for molecular analysis. Well-spread metaphase plates were obtained in 18/40 (45%) cases for analysis. RT-PCR revealed abnormal genes in 20/40 (50%) patients. The results of molecular cytogenetic analysis were correlated with patients’ clinical and hematological parameters for risk stratification and immediate outcome (induction of remission). Eighteen out of 40 (45%) cases revealed no abnormality. Among the remaining 22 cases, 8 had TEL–AML1 (20%), 6 had BCR–ABL (15%), 4 had MLL–AF4 (10%), 2 had E2A–PBX1 (5%) fusion genes, and 2 had hyperdiploidy. To conclude, a higher proportion of cases in this study showed adverse translocations such as t (9;22), t (4;11), and t (1;19) compared to that reported in literature.

Conclusion: RT-PCR assay was useful in detecting the prognostically significant oncogene fusion transcripts. In our study of 40 patients, we found that the pattern and frequency differ from those reported in Western literature. Our study reveals a lower frequency of hyperdiploidy (5%) and a higher frequency of BCR–ABL gene fusion (20%) in childhood ALL. Above all, in contrast to previous studies on childhood ALL, our study showed female predominance, with the male-to-female ratio being 0.8 : 1. Apart from the BCR–ABL fusion gene, none other was associated with poor prognosis. It is already well established that the characterization of the genetic entities at diagnosis is crucial for the understanding and the optimal treatment of ALL. Because the aberrations in our population differ significantly from those reported in Western populations, we may be required to tailor our protocols.



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