Markers of apoptosis and proliferation related gene products as predictors of treatment outcome in childhood acute lymphoblastic leukemia.
The aim of the study is to characterize markers of apoptosis in children with acute lymphoblastic leukemia (ALL) in relation to treatment outcome of the disease. The study was performed on 34 children with ALL and 39 healthy children as a control group. Apoptosis was assessed by cell morphology; DNA fragmentation; ELISA and RT-PCR for CD95, CD95L, BcL-2 and nuclear factor-kappa B (NF-kappaB); and flow cytometry for CD95, CD40, CD49d and CD11a. Apoptosis was significantly lower in patients than controls. Apoptosis detected by CD95 ligand was significantly lower in cases with no remission after treatment than those who achieved remission. Anti-apoptotic factors: CD40, BcL-2, and NF-kappaB were all found to be higher in cases than controls and in cases with no remission than those achieved remission. CD49d was significantly lower in cases than controls, and significantly lower in cases with who did not achieve remission. CD11a levels were similar in the various groups. Delayed apoptosis of ALL cells is genetically controlled either directly or indirectly by a network of oncogenes and tumor suppressor genes. CD40 appeared to stimulate both T and B lineage and is considered the most potent influencer and predictor of resistance to therapy. Inhibitors for the activity of CD40, Bcl-2 and NF-kappaB as well as stimulants to CD95 could have a potential therapeutic benefit.
Hafez
Mohammad
M
Department of Pediatrics, Faculty of Medicine, University of Mansoura, Mansoura, Egypt.
Al-Tonbary
Youssef
Y
El-Bayoumi
Mohammed A
MA
Hatem
Nadia
N
Hawas
Samia
S
Mansour
Ahmed
A
Marzouk
Iman
I
Hafez
Mona M
MM
Yahia
Sohier
S
Farahat
Nahla
N
D017209:Apoptosis / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis; D019013:CD40 Antigens; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D008297:Male; D009857:Oncogenes; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis
D015415:Biomarkers; D019013:CD40 Antigens