Potential role for wild-type p53 in leukemias with MLL gene translocations

Oncogene
M D MegonigalC A Felix

Abstract

We used single-strand conformation polymorphism (SSCP) analysis of p53 exons 4-8 to screen for possible mutations in 25 pediatric de novo leukemias with translocations of the MLL gene at chromosome band 11q23. Of the 25 patients, 21 were infants. Fifteen cases were acute myeloid leukemia (AML), eight were acute lymphoblastic leukemia (ALL), and two cases were biphenotypic. Nineteen cases were studied at diagnosis and six at time of relapse. p53 mutations were absent in all 19 cases studied at the time of diagnosis. The only mutation was a TGC-->TTC transversion (cys-->phe) at codon 141 in exon 5 in a case of infant ALL at relapse that occurred by subclone evolution after MLL gene translocation. We previously showed that p53 mutations are also absent in pediatric treatment-related leukemias with MLL gene translocations. The absence of p53 mutations at initial transformation may suggest that the anti-apoptotic effect of mutant p53 is not important in leukemias with MLL gene translocations. Alternatively, exogenous DNA damage may be the common feature in treatment-related and de novo cases. Since MLL gene translocations may occur through DNA repair and wild-type p53 is central to DNA repair, the absence of p53 mutations raises the...Continue Reading

Citations

Sep 28, 1998·Biochimica Et Biophysica Acta·C A Felix
Mar 7, 2002·Journal of Pediatric Hematology/oncology·J GumpS P Hunger
Apr 3, 2009·Genes & Development·Johannes ZuberScott W Lowe
Jun 19, 2009·Haematologica·Robert K Slany
Mar 8, 2000·Proceedings of the National Academy of Sciences of the United States of America·M D MegonigalC A Felix
Jun 10, 2000·British Journal of Haematology·C H Pui, M V Relling
May 8, 2001·Medical and Pediatric Oncology·C A Felix
Jan 27, 2005·Cancer Letters·Christine Richardson
Sep 15, 2016·Science Signaling·Isabel Morgado-PalacinOscar Fernandez-Capetillo
May 29, 2002·Oncogene·Joseph M ScanduraStephen D Nimer
Oct 28, 2019·Nature Communications·Yasutaka HayashiToshio Kitamura
Sep 28, 2000·Cancer Treatment Reviews·A NgO B Eden

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