The serum TRAIL and TRAIL ligand on the apopitotic pathway in childhood acute leukemias

Aim: In leukemias and malignant tumors the balance and interaction betweenapoptosis and cell proliferation is dysregulated. Many types of cancer cells have tumornecrosis factor related apoptosis inducing ligand (TRAIL) on their cell membransurfaces. Targeting the cell extrinsic pathway which triggers p-53 independent apoptosisoffers a unique therapeutic stragtegy to induce apoptosis in only cancer cells thusprevents the damage of healthy cells. TRAIL induces apoptosis with its receptorsTRAIL-R1, TRAIL-R2 however apoptosis can not be induceed by receptorsTRAIL R-3 and TRAIL-R4. Ther are many trials to search the correlation betweenleukemia and apoptotic pathway disorders.In this study we determined the seum levels of TRAIL and TRAIL receptors(TRAIL-R1, TRAIL-R2, TRAIL-R3, TRAIL-R4 ) in acute childhood leukemias atdiagnosis. We aimed to determine the relation between the levels of soluble TRAIL andTRAIL receptors and patient?s survival, clinical parameters.Materials and Methods: The study was performed in Pediatric Hematology andPediatric Oncology department of Çukurova University Medical Faculty betweenOctober 2009 and July 2010. Twenty-three cases with ALL at the ages of 9 months-12year 8 months and fourteen cases with AML at the ages of 9 days-19 years are includedin this study. The age distrubution of the control group varied 3 months-17 yearsconsisted of twenty-one healty children with similar gender and age were included inthe study. In this study we investigated serum TRAIL and TRAIL receptor levels byusing ELISA method and device elisa plate reader.Results: The comparison of the average values of the TRAIL levels in acuteleukemia patients and control group have shown that patients with leukemia have lowsoluble TRAIL levels (p=0.002) (p<0.05).The comparison of the average values of the TRAIL levels in ALL and AMLpatients have shown no difference (p>0.05).In patients with HRG of ALL have shown low soluble TRAIL levels (p=0.08)(p<0.05), In patients with CALLA- B ALL have shown low soluble TRAIL levels(p=0.04) (p<0.05).Children with acute leukemias (ALL, AML) who died during treatment haveshown low levels of serum TRAIL (p=0.04) (p<0.05).The patients with AML who survived have shown high levels of serumTRAIL-R1 (p=0.03) (p<0.05).In ALL group we found high levels of TRAIL-R3 (p=0.04) (p<0.05).Conclusion: This study indicate that children with leukemias (AML, ALL) havelow levels of soluble TRAIL. In children with HRG ALL and CALLA- B ALL havelow levels of soluble TRAIL. These results indicate that apoptosis may not be induced in this two groups which have poor prognosis. In ALL patients the receptor TRAIL-R3levels were high. The low levels of sTRAIL and high levels of TRAIL-R3 decoyreceptors suggest that apoptosis can not be induced and this may be related in thepathogenesis of ALL.We found high serum TRAIL-R1 levels in AML patients who survived.As a result, soluble TRAIL and TRAIL receptors might play a role inleukomogenesis. However many investigations are needed involving determination ofthe inner cell mRNA levels and cell surface levels of TRAIL and TRAIL receptors tosuggest soluble TRAIL?s and TRAIL receptor?s role in leukomegenesis..Key words: Apoptosis, ALL, AML, TRAIL, TRAIL-R1, TRAIL-R2, TRAIL-R3,TRAIL-R4