Role of GSTM1 (Present/Null) and GSTP1 (Ile105Val) polymorphisms in susceptibility to acute lymphoblastic leukemia among the South Indian population.

Acute lymphoblastic leukaemia (ALL) is the most common pediatric malignancy worldwide. The origin of this disease may be explained by a combination of genetic and environmental factors. Glutathione-s-transferases are a multi-gene family of enzymes involved in the detoxification of a wide variety of environmental carcinogens. A total of 92 immunophenotyped cases (below 25 years of age) and 150 cord blood controls were here analysed by PCR for GSTM1(Present/Null) and RQ-PCR allelic discrimination assay for GSTP1(Ile105Val). We found a significant increased risk for ALL with the GSTM1 null genotype (OR: 1.96, 95%CI=1.08-3.57), but no significant risk was found with the GSTP1 (Ile/Val) genotype (OR: 1.32, 95%CI = 0.74-2.37) and the GSTP1 Val/Val genotype (OR: 1.41, 95%CI=0.5-3.96) alone. Combined analysis of GSTM1 and GSTP1 showed significant higher risk associated with the GSTM1 (null/null) and GSTP1 [(Ile/Val)/ (Val/Val)] genotype (OR=2.78: 95%CI=1.16-6.69).

Does TAL-1 deletion contribute to the high incidence of T-cell acute lymphoblastic leukemia in South Indian patients?

BACKGROUND: The incidence of T-cell acute lymphoblastic leukemia (T-ALL) in South India is very high (43.1%) when compared to the Western countries (10-20%). TAL-1 deletion is the most common genetic abnormality in T-ALL. OBJECTIVES: The present study was aimed to detect the incidence of type 1 and type 2 TAL-1 deletions and assess whether they might contribute to the high incidence of T-ALL in South India. MATERIALS AND METHODS: 45 cases of T-ALL (pediatric-32, adolescents-7 and young adults-6) were studied by DNA-PCR and sequencing. Age of the patients ranged from 3 yrs to 29 yrs (median age 14 yrs). RESULTS: TAL-1 deletion type 1 was detected in 6 (13.3%) cases (3 pediatric and 3 adolescents) and all were males. TAL-1 deletion type 2 was not present. Comparing the clinical features and immunological marker analysis of TAL-1 deletion positive and negative cases did not show any significant differences except in the WBC count, which was significantly higher in cases showing TAL-1 deletion (>100 x 109/L, p value= 0.003). All the positive cases of TAL-1 deletion were confirmed by sequencing, the results showing that the fusion region at SIL gene and TAL-1 gene contained an average 'N region' insertion of 7.8 nucleotides. The numbers of nucleotides deleted at the 5' end and 3' end of TAL-1 gene were averages of 3 and 1, respectively. CONCLUSION: Though the incidence of T-ALL is high in South India, the frequency of TAL-1 deletion and their fusion gene sequences are not unique and are similar to those reported in other ethnic and geographic populations. Hence the present study indicates that TAL-1 deletion alone does not contribute to the high incidence of T-ALL in South Indian patients.

Type 1 (11;22)(q24:q12) translocation is common in Ewing's sarcoma/peripheral neuroectodermal tumour in south Indian patients.

The Ewing's sarcoma family can present diagnostic difficulties. In the past the basis of diagnosis has been a exclusion. Identification of a specific translocation especially t(11;22) (EWS-FLI 1 fusion gene), which is seen in nearly 85 percent of Ewing's sarcoma cases can help in precise diagnosis. We have carried out a study on twenty patient samples diagnosed to have Ewing's sarcoma/peripheral neuroectodermal tumour (PNET)/small round cell malignant tumour. The study involved RT-PCR analysis for the fusion transcript, followed by sequencing to identify the specific type of fusion. Ninety percent (18/20) of the samples tested were found to be t(11;22) translocations involving EWS-FLI 1 genes. Sixty-one percent (11/18) were found to be type 1 fusion and seven were type 2 (39 percentage). This is the first study in India with quantitative information about the types of EWS-FLI 1 translocations present in Ewing's family of tumours in south Indian patients.

Characterization of mouse fibroblast (NIH3T3) and fibrosarcoma cell lines (WEHI-164 and MFS 8) using PMRS.

Proton magnetic resonance Spectroscopy (PMRS) has been used to study the differences between immortalized fibroblasts and fibrosarcoma cells of different grade. One and two dimensional purged correlation spectroscopy (PCOSY) have been used to assess intact viable fibroblast and fibrosarcoma cells, and differences in the triglyceride, cellular metabolite, and cell surface fucosylation patterns between the three cell lines have been observed. The clinical implication of this study is the potential use of PMRS as an adjunct to conventional histopathology.

Induction chemotherapy in non-metastatic high grade osteo sarcomas--results of pilot study at Cancer Institute (WIA), Madras.

Twelve patients with high grade osteosarcomas of the extremities were treated with two cycles of induction chemotherapy using adriamycin and cis-platinum and sandwich radiation between the two cycles (4000 rads). Ten patients underwent amputation or disarticulation, two patients had wide excision followed by endoprosthesis. The specimen was assessed for grade of necrosis. The Disease Free Survival at a minimum follow-up period of 26 months and median follow-up period of 35.5%. All the five patients who developed distant metastases had shown only a grade I necrosis in the tumour.