TY - JOUR
T1 - MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia
AU - Garzon, Ramiro
AU - Volinia, Stefano
AU - Liu, Chang Gong
AU - Fernandez-Cymering, Cecilia
AU - Palumbo, Tiziana
AU - Pichiorri, Flavia
AU - Fabbri, Muller
AU - Coombes, Kevin
AU - Alder, Hansjuerg
AU - Nakamura, Tatsuya
AU - Flomenberg, Neal
AU - Marcucci, Guido
AU - Calin, George A.
AU - Kornblau, Steven M.
AU - Kantarjian, Hagop
AU - Bloomfield, Clara D.
AU - Andreeff, Michael
AU - Croce, Carlo M.
PY - 2008/3/15
Y1 - 2008/3/15
N2 - MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are negative regulators of gene expression. To determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in acute myeloid leukemia (AML), we evaluated the miRNA expression of CD34+ cells and 122 untreated adult AML cases using a microarray platform. After background subtraction and normalization using a set of housekeeping genes, data were analyzed using Significance Analysis of Microarrays. An independent set of 60 untreated AML patients was used to validate the outcome signatures using real-time polymerase chain reaction. We identified several miRNAs differentially expressed between CD34+ normal cells and the AML samples. miRNA expression was also closely associated with selected cytogenetic and molecular abnormalities, such as t(11q23), isolated trisomy 8, and FLT3-lJD mutations. Furthermore, patients with high expression of miR-191 and miR-199a had significantly worse overall and event-free survival than AML patients with low expression (overall survival: miR-191, P = .03; and miR-199a, P = .001, Cox regression). In conclusion, miRNA expression in AML is closely associated with cytogenetics and FLT3-lTD mutations. A small subset of miRNAs is correlated with survival.
AB - MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are negative regulators of gene expression. To determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in acute myeloid leukemia (AML), we evaluated the miRNA expression of CD34+ cells and 122 untreated adult AML cases using a microarray platform. After background subtraction and normalization using a set of housekeeping genes, data were analyzed using Significance Analysis of Microarrays. An independent set of 60 untreated AML patients was used to validate the outcome signatures using real-time polymerase chain reaction. We identified several miRNAs differentially expressed between CD34+ normal cells and the AML samples. miRNA expression was also closely associated with selected cytogenetic and molecular abnormalities, such as t(11q23), isolated trisomy 8, and FLT3-lJD mutations. Furthermore, patients with high expression of miR-191 and miR-199a had significantly worse overall and event-free survival than AML patients with low expression (overall survival: miR-191, P = .03; and miR-199a, P = .001, Cox regression). In conclusion, miRNA expression in AML is closely associated with cytogenetics and FLT3-lTD mutations. A small subset of miRNAs is correlated with survival.
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U2 - 10.1182/blood-2007-07-098749
DO - 10.1182/blood-2007-07-098749
M3 - Article
C2 - 18187662
AN - SCOPUS:42449141513
SN - 0006-4971
VL - 111
SP - 3183
EP - 3189
JO - Blood
JF - Blood
IS - 6
ER -