Bcl-2 family members in childhood acute lymphoblastic leukemia: Relationships with features at presentation, in vitro and in vivo drug response and long-term clinical outcome

G. S. Salomons, L. A. Smets, M. Verwijs-Janssen, A. A.M. Hart, E. G. Haarman, G. J.L. Kaspers, E. R. Van Wering, A. Van Der Does-Van Den Berg, W. A. Kamps

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74 Citaten (Scopus)

Samenvatting

We have found that, in addition to Bcl-2 and Bax, the expression levels of apoptosis inducers (Bad, Bak) and inhibitors (Bcl-x(L), Mcl-1) were highly variable in blasts from 78 children with newly diagnosed acute lymphoblastic leukemia (ALL). The patients were enrolled in the national study ALL-7 of the Dutch Childhood Leukemia Study Group. In contrast to Bcl-2 that inversely correlated with %S-phase cells and WBC, and was lower in T than in B-lineage ALL, the Bcl-2 family members were not found to be associated with features at presentation. These expression levels were also compared with drug resistance in in vitro MTT (methyl-thiazol-tetrazolium) assays for prednisolone, vincristine and asparaginase in 46 children. Protein expression levels of the Bcl-2 family were not found to correlate with in vitro resistance to the individual drugs or the combined drug resistance profile. In addition, neither peripheral blast reduction after 1 week of prednisone monotherapy nor long-term disease-free interval or survival showed a correlation with protein expression. Our results indicate that the anti-proliferative function of Bcl-2 dominates its anti-apoptotic function in ALL, but neither Bcl-2 nor the Bcl-2 family members gained prognostic information in the risk-adapted protocol ALL-7.

Originele taal-2Engels
Pagina's (van-tot)1574-1580
Aantal pagina's7
TijdschriftLeukemia
Volume13
Nummer van het tijdschrift10
DOI's
StatusGepubliceerd - 1999
Extern gepubliceerdJa

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