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.
Department of Medical Oncology, Nizams Institute of Medical Sciences, Hyderabad, Andhra Pradesh.
Sailaja
S
Kagita
Department of Medical Oncology, Nizams Institute of Medical Sciences, Hyderabad, Andhra Pradesh.
Srihari
S
Uppalapati
Department of Medical Oncology, Nizams Institute of Medical Sciences, Hyderabad, Andhra Pradesh.
Sadasivudu
S
Gundeti
Department of Medical Oncology, Nizams Institute of Medical Sciences, Hyderabad, Andhra Pradesh Homi Bhabha Cancer Hospital and Research Centre, Visakapatnam, Andhra Pradesh, India rdigumarti@gmail.com.
Raghunadharao
R
Digumarti
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002454:Cell Differentiation; D019008:Drug Resistance, Neoplasm; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D007532:Isoleucine; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D013912:Threonine
D000970:Antineoplastic Agents; D001549:Benzamides; D022763:CCAAT-Enhancer-Binding Protein-alpha; D010879:Piperazines; D011743:Pyrimidines; D007532:Isoleucine; D013912:Threonine; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
BCR-ABL TK mutations; C/EBPα; chronic myeloid leukaemia; expression; imatinib; response