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Specific expression of the annexin VIII gene in acute promyelocytic
leukemia
KS Chang, G Wang, EJ Freireich, M Daly, SL Naylor, JM Trujillo and SA Stass
Division of Laboratory Medicine, University of Texas, M.D. Anderson Cancer
Center, Houston 77030.
Since the translocation breakpoint t(15;17) (q22;q21) in acute
promyelocytic leukemia (APL) occurs within the retinoic acid receptor-
alpha (RARA) gene, the expression of many genes normally regulated by RARA
may be affected by this translocation. To identify genes that may be
aberrantly expressed in APL, a subtraction cDNA library of an APL patient
with t(15;17) was constructed. A cDNA, pRD1, specifically expressed in APL
was identified. DNA sequence analysis of pRD1 showed that this gene is
similar to the DNA sequence of annexin VIII, a gene which encodes a
vascular anticoagulant. The annexin VIII gene was assigned to chromosome
10, which indicates that specific expression of this gene in APL is not
directly involved in the t(15;17) breakpoint region. We have analyzed the
expression of annexin VIII gene in nine t(15;17)-positive APL patients and
one APL patient with a chromosome 17q-abnormality. We found that all APL
samples expressed high levels of the annexin VIII gene. Expression of the
annexin VIII gene in all other leukemias, including acute myelogenous
leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, and
acute lymphoblastic leukemia, was undetectable, except in one patient with
acute myelogenous leukemia in which a very low level of expression was
detected. Annexin VIII is highly expressed in the APL cell line, NB4. Its
expression was significantly reduced after 8 hours of all-trans retinoic
acid (ATRA) treatment, whereas the expression of RARA increased
several-fold within 4 hours postinduction. Thus, increased expression of
RARA preceded the downregulation of annexin VIII after ATRA induction,
suggesting an inverse relationship between RARA and annexin VIII
expression. Since increased expression of the fusion transcript was seen
after ATRA induction and an APL without a t(15;17) translocation expressed
high levels of annexin VIII, it appears that increased expression of
annexin VIII in APL is not related to the fusion transcript. Therefore,
dysregulation of the RARA gene may be related to the overexpression of
annexin VIII in APL.
Volume 79,
Issue 7,
pp. 1802-1810,
04/01/1992
Copyright © 1992 by The American Society of Hematology
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