Identification of clinically important chromosomal aberrations in acute myeloid leukemia by array-based comparative genomic hybridization.
Array-based comparative genomic hybridization (aCGH) chromosomal analysis facilitates rapid detection of cytogenetic abnormalities previously undetectable by conventional cytogenetics. In this study, we analyzed 48 uniformly treated patients with acute myeloid leukemia (AML) by 44K aCGH and correlated the findings with clinical outcome. aCGH identified previously undetected aberrations, as small as 5 kb, of currently unknown significance. The 36.7 Mb minimally deleted region on chromosome 5 lies between 5q14.3 and 5q33.3 and contains 634 genes and 15 microRNAs, whereas loss of chromosome 17 spans 3194 kb and involves 342 genes and 12 microRNAs. Loss of a 155 kb region on 5q33.3 (p < 0.05) was associated with achievement of complete remission (CR). In contrast, loss of 17p11.2-q11.1 was associated with a lower CR rate and poorer overall survival (Kaplan-Meier analysis, p < 0.0096). aCGH detected loss of 17p in 12/48 patients as compared to 9/48 by conventional karyotyping. In conclusion, aCGH analysis adds to the prognostic stratification of patients with AML.
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center , Houston, TX , USA.
Meenakshi
M
Mehrotra
Rajyalakshmi
R
Luthra
Farhad
F
Ravandi
Rachel L
RL
Sargent
Bedia A
BA
Barkoh
Ronald
R
Abraham
Bal Mukund
BM
Mishra
L Jeffrey
LJ
Medeiros
Keyur P
KP
Patel
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods*; D003561:Cytarabine / Q000008:administration & dosage; D056915:DNA Copy Number Variations; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D059785:Karyotype; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D011379:Prognosis; D012074:Remission Induction
D003561:Cytarabine; D015255:Idarubicin
AML; Array comparative genomic hybridization; RNF145; TP53; chromosome regions 5q and 17p