Copy number variations in normal karyotype acute myeloid leukaemia and their association with treatment response.
Copy number variation (CNV) has been reported to be associated with chemotherapy response, which affects disease prognosis. Here, we determined the frequency of genome-wide cytogenetic CNV aberrations in Korean patients with normal karyotype (NK) acute myeloid leukaemia (AML) and tested whether these genomic variations contribute to differences in Ara-C and anthracycline-based chemotherapy responses. Bone marrow aspirates and blood from 30 previously untreated de novo NK-AML patients were provided at the time of diagnosis for copy number analysis. Possible associations between cytogenetic aberrations and clinical parameters were analysed. CNVs were identified in 23 (76.7%) of the 30 cases tested. Multivariate analyses controlled for other clinical co-variates showed that patients having copy number loss had a decreased probability of complete remission (OR, 0.015 [95% CI, 0-0.737], p = 0.035). Patients who had a copy number gain of more than four regions tended to have shorter event-free survival (EFS) (p = 0.083) with multivariate analysis showing that CNV increase is an independent predictive factor for shorter EFS (HR, 22.104 [95% CI, 1.644-297.157], p = 0.020). In addition, we identified candidate genes that may be involved in Ara-C and anthracycline drug response in Korean patients with NK-AML. These results suggest that CNVs may affect the success of Ara-C and anthracycline-based chemotherapy in Korean patients with NK-AML.
College of Pharmacy, Seoul National University, Seoul, Korea.
Kyung Im
KI
Kim
Tae-Kyung
TK
Kim
In-Wha
IW
Kim
Kwang-Sung
KS
Ahn
Sung-Soo
SS
Yoon
Wan Gyoon
WG
Shin
Jung Mi
JM
Oh
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D056915:DNA Copy Number Variations; D019008:Drug Resistance, Neoplasm; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000627:therapeutic use; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D056910:Republic of Korea; D016019:Survival Analysis; D055815:Young Adult
D000970:Antineoplastic Agents; D003561:Cytarabine; D015255:Idarubicin