Contributions
Abstract: PB1610
Type: Publication Only
Background
Studies have shown that approximately 30 to 35 % of pediatric ALL cases are known to harbor genetic abnormalities in cell differentiation, cell cycle control and apoptosis related genes. These genetic abnormalities are prognostically important changes that can influence treatment outcome. Their early recognition is important to individualize treatment decisions and improve overall survival.
Aims
To note the frequency of cell cycle regulatory gene copy number abnormalities in pediatric Acute Lymphoblastic Leukemia (ALL) cases using MLPA assay and to correlate the copy number abnormality status with response to chemotherapy and outcome parameters.
Methods
87 prospectively diagnosed and confirmed ALL cases were enrolled and cell cycle regulatory gene deletions (CDKN2A/2B and RB1) were noted by MLPA assay using ALL-P-335 kit and data analyzed by Coeffalyzer software. In addition clinical and outcome data was recorded as per treatment record files. Ethical clearance of study was obtained from Institute's Ethics Committee.
Results
Mean age in the study group was 5.87 years (6 months – 12 years) with a M;F ratio of 2:1. There were 74 B-ALL and 13 T-ALL cases. The mean TLC in our study group was 1,08,499/cu mm and Good Prednisolone response at day 8 was noted in 70 (81.4%) cases. Day 35 post induction showed M1 response in 82(95.3%) children and M2+M3 response in a total of 4(4.7%) children, while data available in 73 B-ALL and 5 T-ALL cases showed MRD >0.01% in 21(28.7%) B-ALL and 1 T-ALL case respectively. 44.8% of children in the cohort had cell cycle regulatory gene copy number abnormalities of which frequency of CDKN2A/2B gene copy number abnormalities (both B and T cell ALL) was 43.6% and frequency of RB1 gene copy number abnormalities was 3.4% (p value-0.00). All the T cell ALL (100%) cases in the cohort had cell cycle regulatory gene copy number abnormalities, compared to 35.1% in B cell ALL cases (p value - 0.00). In addition predominantly homozygous CDKN2A/2B gene deletions in T-ALL (92%) as compared to B-ALL (48%) were noted (p - 0.00). On correlation of cell cycle regulatory gene deletional versus non deletional group with standard ALL risk factors and treatment outcome parameters, a significant correlation was noted of deletional group with high TLC (p -0.00 ), T-ALL phenotypes (p -0.00 ), events (p -0.28 ) and BCR-Abl gene positivity (p – 0.00). The mean EFS duration was further decreased by 8.1 months in cases with only CDKN2A/2B gene deletions in comparison with those without cell cycle regulatory gene copy number abnormalities. (p value-0.00 ).
Conclusion
Our study results highlight that CDKN2A/2B deletions are common in B-ALL and seen in high frequency in T-ALL (100%) our study. Moreover CDKN2A/2B deletions in B-ALL confer a poor EFS in multivariate analysis suggesting their potential role as a poor prognostic marker in B-ALL.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Acute lymphoblastic leukemia
Abstract: PB1610
Type: Publication Only
Background
Studies have shown that approximately 30 to 35 % of pediatric ALL cases are known to harbor genetic abnormalities in cell differentiation, cell cycle control and apoptosis related genes. These genetic abnormalities are prognostically important changes that can influence treatment outcome. Their early recognition is important to individualize treatment decisions and improve overall survival.
Aims
To note the frequency of cell cycle regulatory gene copy number abnormalities in pediatric Acute Lymphoblastic Leukemia (ALL) cases using MLPA assay and to correlate the copy number abnormality status with response to chemotherapy and outcome parameters.
Methods
87 prospectively diagnosed and confirmed ALL cases were enrolled and cell cycle regulatory gene deletions (CDKN2A/2B and RB1) were noted by MLPA assay using ALL-P-335 kit and data analyzed by Coeffalyzer software. In addition clinical and outcome data was recorded as per treatment record files. Ethical clearance of study was obtained from Institute's Ethics Committee.
Results
Mean age in the study group was 5.87 years (6 months – 12 years) with a M;F ratio of 2:1. There were 74 B-ALL and 13 T-ALL cases. The mean TLC in our study group was 1,08,499/cu mm and Good Prednisolone response at day 8 was noted in 70 (81.4%) cases. Day 35 post induction showed M1 response in 82(95.3%) children and M2+M3 response in a total of 4(4.7%) children, while data available in 73 B-ALL and 5 T-ALL cases showed MRD >0.01% in 21(28.7%) B-ALL and 1 T-ALL case respectively. 44.8% of children in the cohort had cell cycle regulatory gene copy number abnormalities of which frequency of CDKN2A/2B gene copy number abnormalities (both B and T cell ALL) was 43.6% and frequency of RB1 gene copy number abnormalities was 3.4% (p value-0.00). All the T cell ALL (100%) cases in the cohort had cell cycle regulatory gene copy number abnormalities, compared to 35.1% in B cell ALL cases (p value - 0.00). In addition predominantly homozygous CDKN2A/2B gene deletions in T-ALL (92%) as compared to B-ALL (48%) were noted (p - 0.00). On correlation of cell cycle regulatory gene deletional versus non deletional group with standard ALL risk factors and treatment outcome parameters, a significant correlation was noted of deletional group with high TLC (p -0.00 ), T-ALL phenotypes (p -0.00 ), events (p -0.28 ) and BCR-Abl gene positivity (p – 0.00). The mean EFS duration was further decreased by 8.1 months in cases with only CDKN2A/2B gene deletions in comparison with those without cell cycle regulatory gene copy number abnormalities. (p value-0.00 ).
Conclusion
Our study results highlight that CDKN2A/2B deletions are common in B-ALL and seen in high frequency in T-ALL (100%) our study. Moreover CDKN2A/2B deletions in B-ALL confer a poor EFS in multivariate analysis suggesting their potential role as a poor prognostic marker in B-ALL.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Acute lymphoblastic leukemia