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Blood, Vol. 93 No. 8 (April 15), 1999:
pp. 2671-2678
Increased BAX Expression Is Associated With an Increased Risk of
Relapse in Childhood Acute Lymphocytic Leukemia
Linda A. Hogarth and
Andrew G. Hall
From The LRF Molecular Pharmacology Specialist Programme, Cancer
Research Unit, Medical School, Newcastle Upon Tyne, UK.
Studies in cell lines have indicated that expression of the BCL-2
family of proteins is an important determinant of chemotherapy-induced apoptosis; however, the level of expression of these proteins in
childhood acute lymphoblastic leukemia (ALL) has not been extensively reported. Using quantitative Western blotting we have determined the
level of expression of BCL-2, BAX, MCL-1, and BCL-X in lymphoblasts from 47 children with ALL (33 at presentation only, 4 at relapse only,
and 10 at both presentation and on relapse). Results were determined as
a ratio to actin as an internal control. BCL-2, BAX, and MCL-1 were
detected in all samples. BCL-XL was only detected in 6 cases (4 at presentation and 2 at relapse) and BCL-XS in none. No correlation was found between expression and white blood cell
count, age at diagnosis, gender, or blast karyotype. BCL-2 levels and
the BCL/BAX and MCL-1/BAX ratios were found to be significantly higher
in B-lineage as compared with T-lineage disease (P < .003, .02, and .02, respectively). No consistent pattern of change in expression was noted in the 10 cases studied at both presentation and
relapse. Kaplan-Meier analysis showed a significant correlation between
high BAX expression and an increased probability of relapse (P < .05 by the log rank test), suggesting that chemosensitivity in
leukemic blasts may be regulated by factors that override the BCL-2 pathway.
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