Cellular expression of antiapoptotic BCL-2 oncoprotein in newly diagnosed childhood acute lymphoblastic leukemia: a Children's Cancer Group Study.
We found a marked variation in BCL-2 oncoprotein expression levels of primary leukemic cells from 338 children with newly diagnosed acute lymphoblastic leukemia (ALL). None of the high-risk features predictive of poor treatment outcome in childhood ALL, such as older age, high white blood cell (WBC) count, organomegaly, T-lineage immunophenotype, ability of leukemic cells to cause overt leukemia in severe combined immunodeficient (SCID) mice, presence of MLL-AF4, and BCR-ABL fusion transcripts were associated with high levels of BCL-2 expression. Overall, high BCL-2 levels were not associated with slow early response, failure to achieve complete remission, or poor event-free survival. High BCL-2 levels in primary leukemic cells predicted slow early response only in T-lineage ALL patients, which comprised approximately 15% of the total patient population. Even for this small subset of patients, the level of BCL-2 expression did not have a significant impact on the short-term event-free survival.
Uckun
F M
FM
Biotherapy Institute, University of Minnesota, Roseville 55113, USA.
Yang
Z
Z
Sather
H
H
Steinherz
P
P
Nachman
J
J
Bostrom
B
B
Crotty
L
L
Sarquis
M
M
Ek
O
O
Zeren
T
T
Tubergen
D
D
Reaman
G
G
Gaynon
P
P
D000293:Adolescent; D000328:Adult; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D019254:Genes, bcl-2; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009368:Neoplasm Transplantation; D015514:Oncogene Proteins, Fusion / Q000032:analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D012074:Remission Induction; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D019253:Proto-Oncogene Proteins c-bcl-2