Analysi̇s of prognosti̇c moleculer markers i̇n pedi̇atri̇c acute lymphoblasti̇c leukemi̇a pati̇ents

Acute lymphoblastic leukemia (ALL) is the most common disease group among pediatric cancer cases. Although survival rates are increased in pediatric ALL patients, it is known that deaths occur due to recurrence of the disease (15-20%). ALL genome studies led to defiene various molecular markers that are important in ALL classification and treatment decisions. One of this subtypes, BCR-ABL1-like ALL (Ph-like ALL) is involved in gene activation which effects many tyrosine kinase and cytokine receptors. The CRLF2 (Cytokine Receptor-Like Factor 2) gene is a member of the cytokine receptor family. Approximately half of this new subgroup carry IGH-CRLF2 and P2RY8-CRLF2 rearrangements. Overexpression of the CRLF2 gene has been found as an unfovarable factor and correlated with poor outcome In our cohort, CRLF2 gene variations had been reported in our previous studies. In this thesis, we aimed to quantify CRLF2 mRNA expression in 59 pediatric B-ALL and 11 pediatric T-ALL patients' diagnosed materials by quantitative-real time polymerase chain reaction (RT-PCR), and evaluate prognostic significance. The CRLF2 expression cut-off value (ΔCt) was determined as 8.02. Consequently, CRLF2 overexpression was detected in 11 B-ALL patients (15%). ΔCt≥8.02 represents normal CRLF2 expression level and 48 B-ALL and 11 T-ALL patients had normal CRLF2 expression. Statistical analyzes were performed according to the BFM protocol criterias but there was no statistically significant difference between H-CRLF2 and N-CRLF2 groups. Clinical features of the H-CRLF2 patients; median value of age is 4 years, 6.3% alive, 6.3% no relapse, response to treatment (5.4%), leukocyte count at diagnosis <100,000 (x109 / L), 0.4% high risk and 0.6%low risk group, no CNS involvement. We did not detect any statistical difference for overall survival (cox p = 0.88) and event free survival (cox p = 0.81). CRLF2 overexpression levels were detected by quantitative PCR however, several methods have been used to define a cut-off value for CRLF2 expression in the literature. Herein, we applied different cut-off levels and evaluated statistical analysis. Detection of contitutional alterations in the gene are important for correct separation of patients. In this study, although no clinically significant and prognostic differences were found in cases with Y-CRLF2, it is important to determine Y-CRLF2 cases for the selection of Ph-like patients. In addition, Y-CRLF2 patients are candidates for treatment with JAK inhibitors.