ORIGINAL ARTICLE
Prognostic Significance of CEBPA
Mutations and BAALC Expression in Acute
Myeloid Leukemia Patients with Normal
Karyotype
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Tanta University, Faculty of Medicine, Tanta, Egypt
Publication date: 2010-01-12
Corresponding author
Jehan A. El-Sharnouby
Tanta University, Faculty of Medicine,
Departments of Clinical Pathology Tanta,
Egypt
Eur J Gen Med 2010;7(1):17-28
KEYWORDS
ABSTRACT
Aim: The aim of this work is to study the prognostic impact of mutations
in the myeloid transcription factor gene CEBPA (for CCAAT/enhancer
binding protein-α) and expression of the BAALC gene (for brain
and acute leukemia, cytoplasmic), a novel gene involved in leukemia,
in 38 adults with AML and normal cytogenetics.
Method: Screening for mutations of CEBPA gene was assessed using
PCR-single-strand conformation polymorphism (PCR-SSCP), and BAALC
expression was determined by real-time reverse transcriptase polymerase
chain reaction in blood or bone marrow samples.
Result: CEBPA mutations were found in 7 (18.4%) of 38 patients, 36.8
% (14 of 38) had low BAALC expression and 63.2 % (24 of 38) had high
BAALC expression. Patients with CEBPA mutations had favorable course
of their disease. They had higher rate of complete remission (CR)
(85.7 % vs 51.6 %; p= 0.108), lower incidence of relapse (0% vs 41.9%;
p= 0.038). Disease free survival (DFS) and overall survival (OS) were
significantly longer for patients with CEBPA mutations compared with
patients without mutations (mean 13.65±5.41 vs 7.32±4.33 months,
p= 0.047; mean 15.32±6.5 vs 8.5±3.21 months, p= 0.039; respectively).
Compared to low BAALC expressers, high BAALC expressers had lower
incidence of CR (50% vs 71.4%; p= 0.171), higher incidence of relapse
(50% vs 14.3%; p= 0.029), and showed significantly shorter DFS (mean
7.5±2.12 vs 11.67±4.6 months, p= 0.038) and inferior overall survival
(mean 9.1±3.52 vs 13.22±4.21 months, p= 0.024).
Conclusion: From this study, we can conclude that CEBPA mutation
status and BAALC expression are important prognostic factors in AML
patients with normal cytogenetics and their incorporation into novel
risk-adapted therapeutic strategies will improve the currently disappointing
cure rate of this group of patients.