Time trend in frequency of occurrence of major immunophenotypes in paediatric acute lymphoblastic leukemia cases as experienced by Cancer Institute, Chennai, south India during the period 1989-2009.

Background: Pediatric acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease and socioeconomic and environmental factors are considered to be an important determinant of its immunophenotype. The aim of this analysis is to study the time trend in the immunophenotype of pediatric acute lymphoblastic leukemia (ALL) cases in our geographic setting. Materials and Methods: A total of 639 new pediatric ALL cases immunophenotyped during 1989-2009 forms the basis of this analysis. Representative bone marrow or peripheral blood of these patients was immunophenotyped flowcytometrically using an extensive panel of monoclonal antibodies. Results: During early phase of our study we noticed a relative excess of T-ALL and a paucity of common acute lymphoblastic leukemia (C-ALL) in contrast to western data. Over a period of 20 years we witnessed a gradual reduction in pediatric T-ALL cases and a proportionate increase in C-ALL cases. Conclusion: We find that this change of pattern is synchronizing with the socioeconomic and industrial development prevailing in our geographic setting and suggest a possible link between the predominant immunophenotype of pediatric ALL cases and the environmental and socioeconomic factors prevailing in that locality.

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.

Bone marrow involvement in a primary mediastinal extragonadal non-seminomatous germ cell tumour.

A case of primary mediastinal extragonadal germ cell tumour with involvement of bone marrow, a rare finding, is reported with a review of literature.