Chemosensitivity of TEL-AML1 fusion transcript positive acute lymphoblastic leukemia cells.
The TEL-AML1 fusion which results from a cryptic t(12;21) translocation is the most frequently occurring genetic abnormality in childhood acute lymphoblastic leukemia (ALL) and has been associated with an excellent treatment outcome. In the present study, we examined the FAS/BCL-2 expression profiles and chemosensitivity of primary leukemic cells from children with newly diagnosed t(12;21)TEL-AML1 fusion transcript-positive versus t(12;21)TEL-AML1 fusion transcript-negative standard risk ALL. TEL-AML1(+) ALL cells expressed higher levels of the pro-apoptotic protein Fas and lower levels of the anti-apoptotic protein Bcl2 than TEL-AML1(-) ALL cells, as determined by confocal laser scanning microscopy. TEL-AML1(+) ALL cells were more sensitive to the apoptosis-inducing effects of serum deprivation, dexamethasone and vincristine than TEL-AML1(-) ALL cells. This study provides novel mechanistic insights regarding the chemosensitivity of TEL-AML1(+) ALL cells and provides a cogent explanation for the excellent leukemia-free survival outcome of children with TEL-AML1(+) ALL treated on contemporary chemotherapy programs.
Krishna Narla
R
R
Parker Hughes Cancer Center, Children's Cancer Group ALL Biology Reference Laboratory and Department of Oncology, Parker Hughes Institute, St. Paul, MN 55113, USA.
Navara
C
C
Sarquis
M
M
Uckun
F M
FM
D017209:Apoptosis / Q000187:drug effects; D002648:Child; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D018613:Microscopy, Confocal; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D016895:Culture Media, Serum-Free; D003907:Dexamethasone; D015514:Oncogene Proteins, Fusion; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014750:Vincristine; D019014:fas Receptor; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein