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Microsatellite Instability and Frameshift Mutations in BAX and
Transforming Growth Factor- RII Genes Are Very Uncommon in Acute
Lymphoblastic Leukemia In Vivo But Not in Cell Lines
Jan J. Molenaar,
Bénédicte Gérard,
Cécile Chambon-Pautas,
Hélène Cavé,
Michel Duval,
Etienne Vilmer, and
Bernard Grandchamp
From INSERM U409, Association Claude Bernard, Faculté de
Médecine Xavier Bichat, Paris; and Service d'Hématologie,
Hôpital Robert Debré, Paris, France.
Mutations in the DNA mismatch repair (MMR) system lead to an
instability of simple repetitive DNA sequences involved in several cancer types. This instability is reflected in a high mutation rate of
microsatellites, and recent studies in colon cancer indicate that
defects in MMR result in frequent frameshift mutations in mononucleotide repeats located in the coding regions of BAX and transforming growth factor- (TGF-) receptor genes. Circumstantial evidence suggests that the MMR defect may be involved in some lymphoid
malignancies, although several allelotype analyses have concluded on
the low level of microsatellite instability in acute lymphoblastic
leukemias. To further evaluate the implication of MMR defects in
leukemogenesis, we have studied a series of 98 children with acute
lymphoblastic leukemia and 14 leukemic cell lines using several
indicators of MMR defects. Microsatellite markers were compared between
blast and normal DNA from the same patients and mutations were sought
in mononucleotide repeat sequences of BAX and TGF- receptor II
(TGF- RII). The absence of microsatellite instability
(MI) and the absence of mutations in the genes examined from patient's
leukemic cells contrasted with the observation that half of the cell
lines displayed a high degree of MI and that three of seven of these
mutator cell lines harbored mutations in BAX and/or TGF-
RII. From these results we conclude that MMR defects are very uncommon
in freshly isolated blasts but are likely to be selected for during the
establishment of cell lines.
Blood, Vol. 92 No. 1 (July 1), 1998:
pp. 230-233
© 1998 by The American Society of Hematology.
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