Abstract
BackgroundThe tumor suppressor gene p53 is involved in the control of cell proliferation, particularly in stressed cells. p 53 gene mutations are the most frequent genetic event found in human cancers. Fanconi Anemia (FA) is the most common representative of inherited bone marrow failure syndromes (IBMFS) with a leukemic propensity. P 53 DNA alteration has not been studied before in Egyptian children with FA.Patients and methodswe investigated p53 mutation in the bone marrow and peripheral blood of forty children, FA (n = 10), acquired aplastic anemia (AAA) (n = 10), and immune thrombocytopenia (ITP) as a control (n = 20), using real-time PCR by TaqMan probe assayResultsMutation of p53 gene was demonstrated in the BM of 90% (9/10) of children with FA, compared to 10% (1/10) in AAA (p < 0.001), while, no p53 DNA mutation was seen in the control group. A positive correlation between DNA breakage and presence of p53 mutation was seen in FA (p < 0.02, r0.81).Conclusionmutation of p53 gene in hypoplastic marrow especially FA may represent an early indicator of significant DNA genetic alteration with cancer propensity.
Highlights
Patients with inherited bone marrow failure syndromes (IBMFS) are at increased risk of malignant transformation, possibly due to cell cycle deregulation as marked by the over expression of cell cycle markers as p53 and Ki-67 [1,2]
Mutation of p53 gene was demonstrated in the BM of 90% (9/10) of children with Fanconi Anemia (FA), compared to 10% (1/10) in aplastic anemia (AAA) (p < 0.001), while, no p53 DNA mutation was seen in the control group
We studied the expression of p53 mutation, as a marker of cell cycle dysregulation, in BM of children with FA as well as children with AAA
Summary
Characteristics of the study population are demonstrated in (table 1): Regarding the age, FA children are the youngest one at time of presentaion comparing to AAA and ITP (p < 0.001). FA = Fanconi Anemia; AAA = Acquired Aplastic Anemia, ITP = Immune Thrombocytopenic Purpura ** Highly Significant p < 0.001. Up regulation p53 mutation gene in our FA patients may reflect a state of reaction to cell stress mostly related to DNA damage as previously reported [6]. Expression p 53mutation was significantly up regulated in the marrow samples of FA patients (80%) This probably reflected a functional up-regulation of p53 gene to provide additional protection for cells with damaged and potentially hazardous DNA. List of Abbreviations and symbols AAA: Acquired Aplastic Anemia; BM: Bone Marrow; BMA: Bone Marrow Aspiration; BMB: Bone Marrow Biopsy; FA: Fanconi Anemia; Hb: Hemoglobin; ITP: Immune Thrombocytopenic Purpura; MMC: Mytomycin C test; TLC: total leucocytic; PB: peripheral blood; *: Fischer exact test, *: Significant p-value, **: Highly Significant p-value.
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