Correlation of C/EBPα expression with response and resistance to imatinib in chronic myeloid leukaemia.
OBJECTIVE
Altered differentiation is a common feature of haematopoietic malignancies with poor prognosis. CAAT/enhancer binding protein alpha (C/EBPα) is a key transcription factor that regulates myeloid differentiation. This study is aimed to know the prognostic value of CAAT/enhancer binding protein alpha expression and correlate its expression with response to imatinib therapy.


METHODS
We quantified the expression of C/EBPα gene in 126 chronic myeloid leukaemia samples (82 from newly diagnosed and 44 from imatinib-resistant patients) and 20 control samples. C/EBPα mRNA level was measured by real-time quantitative polymerase chain reaction using the ΔΔCT method.


RESULTS
C/EBPα expression level was significantly lower in the imatinib-resistant group than in the pretreatment and control group (P = 0.0398). Low CAAT/enhancer binding protein alpha levels in the imatinib-resistant group were significantly associated with advanced phase (P = 0.04), with more peripheral blasts (P = 0.0001), high BCR-ABL levels (P = 0.018) and T315I and P-loop mutations (P = 0.0002). In the pretreatment group, low expression showed association with high EUTOS risk score (P = 0.03) and possible partial cytogenetic response (P = 0.010).


CONCLUSIONS
Our results suggest that low expression of CAAT/enhancer binding protein alpha might have a role in the response to imatinib and progression of disease in patients with chronic myeloid leukaemia.
['Kagita|Sailaja|S|', 'Uppalapati|Srihari|S|', 'Gundeti|Sadasivudu|S|', 'Digumarti|Raghunadharao|R|']
D000328:Adult D000368:Aged D000970:Antineoplastic Agents D001549:Benzamides D022763:CCAAT-Enhancer-Binding Protein-alpha D002454:Cell Differentiation D019008:Drug Resistance, Neoplasm D005260:Female D016044:Fusion Proteins, bcr-abl D006801:Humans D000068877:Imatinib Mesylate D007532:Isoleucine D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive D008297:Male D008875:Middle Aged D009154:Mutation D010879:Piperazines D011237:Predictive Value of Tests D011379:Prognosis D011743:Pyrimidines D013912:Threonine
C/EBPα expression response imatinib chronic myeloid leukaemia BCR-ABL TK mutations