Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia.

BACKGROUND

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms' tumor -1 gene is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia.

AIM OF THE WORK

The aim of this work was to study the impact of WT-1 gene expression in the prognosis of ALL.

PATIENTS AND METHODS

This study was conducted on 40 Egyptian children with newly diagnosed ALL who were subjected to full history taking, thorough clinical examination and laboratory investigations including; complete blood count, LDH, BM aspiration, cytochemistry, immunophenotyping, FISH technique for detection of t(12;21) and t(9;22) and assessment of WT-1 Gene by real-time PCR in BM samples at time of diagnosis.

RESULTS

Positive WT-1 gene expression was found in 22 cases (55%) and negative expression in 18 cases (45%). Positive WT-1 gene expression group (n=22) includes 14 males and 8 females with mean age at presentation of 5.261 ± 0.811 while negative WT-1 gene expression group (n=18) includes 12 males and 6 females with mean age at diagnosis of 9.669 ± 3.731 with significantly older age in negative WT-1 gene expression group but no significant differences between positive and negative WT-1 gene expression groups regarding sex and clinical presentations. There were no significant differences in platelets and WBCs counts, hemoglobin and LDH levels and the number of peripheral blood and BM blast cells at diagnosis between positive and negative WT-1 gene expression groups but after induction therapy there were significantly lower BM blast cells in positive WT-1 gene expression group. There were no statistically significant differences between positive and negative WT-1 gene expression groups regarding immunophenotyping and chromosomal translocations including t(12;21) and t(9;22). There were a significantly higher relapse and death rate and a lower rate of CR, DFS, and OAS in negative WT-1 gene expression group. MRD at end of induction therapy was found in 14 cases out of 40 patients. There were significantly higher number of patients with MRD+ in negative WT-1 gene expression group (After the therapy 20 out of 22 (89%) patients with positive WT-1 gene expression attained a negative MRD, while only 6 out of 18 (33%) with negative WT-1 attained a negative MRD) (p-value = 0.006).

CONCLUSIONS AND RECOMMENDATION

WT-1 gene expression is an important prognostic factor in patients with ALL, being able to prognosticate a negative MRD. Therefore, we can recommend its incorporation into novel risk-adapted therapeutic strategies in patients with ALL.