TY - JOUR
T1 - Genetic changes including gene copy number alterations and their relation to prognosis in childhood acute myeloid leukemia
AU - Armengol, Gemma
AU - Canellas, Anna
AU - Álvarez, Yolanda
AU - Bastida, Pilar
AU - Toledo, José Sánchez De
AU - Pérez-Iribarne, Maria Del Mar
AU - Camós, Mireia
AU - Tuset, Esperanza
AU - Estella, Jesú
AU - Coll, María Dolores
AU - Caballín, María Rosa
AU - Knuutila, Sakari
PY - 2010/1/1
Y1 - 2010/1/1
N2 - We studied a series of 68 subjects diagnosed with childhood acute myeloid leukemia (AML) using conventional cytogenetics and fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) to analyze mutations in FLT3 and NPM1 genes, and/or array comparative genomic hybridization (CGH). Cytogenetic/FISH abnormalities were observed in 71% of subjects, FLT3-ITD mutations in 15%, and NPM1 mutations in 13%. The array CGH alterations (average 3.6 per case) were observed in 96% of the tested subjects. The most frequent alterations were gains of 8q24.3 and 11p15.5-p15.4 in 16% of the samples. Six genes (AKT1, RUNX1, LTB, SDC1, RUNX1T1, and JAK2) from the imbalanced regions have been reported to be involved in AML, whereas other 30 cancer genes, not previously reported in an AML context, were identified as imbalanced. They probably correspond to non passenger alterations that cooperate with the recurrent translocations. The clinical data and genetic changes were tested to find out the possible association with prognosis. Genomic instability (four or more genomic imbalances) was correlated with poor patient outcome (p=0.029). © 2010 Informa Healthcare USA, Inc.
AB - We studied a series of 68 subjects diagnosed with childhood acute myeloid leukemia (AML) using conventional cytogenetics and fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) to analyze mutations in FLT3 and NPM1 genes, and/or array comparative genomic hybridization (CGH). Cytogenetic/FISH abnormalities were observed in 71% of subjects, FLT3-ITD mutations in 15%, and NPM1 mutations in 13%. The array CGH alterations (average 3.6 per case) were observed in 96% of the tested subjects. The most frequent alterations were gains of 8q24.3 and 11p15.5-p15.4 in 16% of the samples. Six genes (AKT1, RUNX1, LTB, SDC1, RUNX1T1, and JAK2) from the imbalanced regions have been reported to be involved in AML, whereas other 30 cancer genes, not previously reported in an AML context, were identified as imbalanced. They probably correspond to non passenger alterations that cooperate with the recurrent translocations. The clinical data and genetic changes were tested to find out the possible association with prognosis. Genomic instability (four or more genomic imbalances) was correlated with poor patient outcome (p=0.029). © 2010 Informa Healthcare USA, Inc.
KW - Array CGH
KW - Childhood AML
KW - Cytogenetics
KW - Genetic mutations
KW - Genomic imbalances
KW - Prognosis
U2 - 10.3109/10428190903350397
DO - 10.3109/10428190903350397
M3 - Article
SN - 1042-8194
VL - 51
SP - 114
EP - 124
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
ER -