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Mutations and loss of expression of a mismatch repair gene, hMLH1, in
leukemia and lymphoma cell lines
A Hangaishi, S Ogawa, K Mitani, N Hosoya, S Chiba, Y Yazaki and H Hirai
Third Department of Internal Medicine, Faculty of Medicine, University of
Tokyo, Japan.
Defects in genes involved in DNA mismatch repair have been detected in both
hereditary and sporadic tumors of colon, endometrium, and ovary and
suggested to be associated with tumorigenesis. To investigate disruptions
of the mismatch repair system in hematological malignancies, we examined
alterations of the human mutL homologue 1 (hMLH1) gene, a member of the
mismatch repair gene family, in a total of 43 human leukemia and lymphoma
cell lines, by polymerase chain reaction-single-strand conformation
polymorphism (PCR-SSCP) and sequencing analyses. Mutations of the hMLH1
gene were detected in three cell lines established from lymphoid leukemias.
Moreover, Northern and Western blot analyses showed that expression of
hMLH1 transcript or protein was abrogated in these three leukemia cell
lines. Further studies for microsatellite loci showed that these cell lines
without hMLH1 expression showed microsatellite instability. This is the
first report that describes mutations and inactivation of the hMLH1 gene in
human leukemia cells, suggesting that disruption of DNA mismatch repair
system may play an important role in the development of human lymphoid
leukemias.
Volume 89,
Issue 5,
pp. 1740-1747,
03/01/1997
Copyright © 1997 by The American Society of Hematology
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