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P53 protein overexpression in de novo acute myeloid leukemia patients with normal diploid karyotype correlates with FLT3 internal tandem duplication and worse relapse‐free survival
Author(s) -
Assi Rita,
Gur Hatice D.,
Loghavi Sanam,
Konoplev Sergej N.,
Konopleva Marina,
Daver Naval,
Tashakori Mehrnoosh,
Kadia Tapan,
Routbort Mark,
Salem Alireza,
KanagalShamanna Rashmi,
Quesada Andres,
Jabbour Elias J.,
Kornblau Steven M.,
Medeiros L. Jeffrey,
Kantarjian Hagop,
Khoury Joseph D.
Publication year - 2018
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.25255
Subject(s) - cytogenetics , myeloid leukemia , bone marrow , karyotype , biology , leukemia , immunohistochemistry , tandem exon duplication , pathology , univariate analysis , medicine , oncology , myeloid , cd34 , cancer research , immunology , gene duplication , multivariate analysis , stem cell , chromosome , gene , genetics
Although ~50% of acute myeloid leukemia (AML) patients have a normal diploid karyotype by conventional cytogenetics at diagnosis, this patient subset has a variable disease course and outcome. Aberrant overexpression of the p53 protein is usually associated with TP53 alterations and a complex karyotype, but the prevalence and impact of p53 overexpression in AML with diploid cytogenetics is unknown. We examined 100 newly diagnosed AML patients to evaluate the impact of p53 expression status quantified in bone marrow core biopsy samples using immunohistochemistry and computer‐assisted image analysis. A total of 24 patients had p53 overexpression defined as 3+ staining intensity in ≥5% of cells; this finding correlated with lower platelet counts ( P = .002), absence of CD34 expression in blasts ( P = .009), higher bone marrow blast counts ( P = .04), and a higher frequency of FLT3 internal tandem duplication ( P = .007). Overexpression of p53 independently predicted for shorter leukemia‐free survival in patients who underwent allogeneic stem cell transplantation by univariate ( P = .021) and multivariate analyses ( P = .004). There was no correlation between MDM2 and p53 protein expression in this cohort. We conclude that p53 expression evaluated by immunohistochemistry in bone marrow biopsy specimens at the time of AML diagnosis may indicate distinct clinical characteristics in patients with normal diploid cytogenetics and is a potentially valuable tool that can enhance risk‐stratification.