Gene expression profiling of pediatric acute myelogenous leukemia.
Contemporary treatment of pediatric acute myeloid leukemia (AML) requires the assignment of patients to specific risk groups. To explore whether expression profiling of leukemic blasts could accurately distinguish between the known risk groups of AML, we analyzed 130 pediatric and 20 adult AML diagnostic bone marrow or peripheral blood samples using the Affymetrix U133A microarray. Class discriminating genes were identified for each of the major prognostic subtypes of pediatric AML, including t(15;17)[PML-RARalpha], t(8;21)[AML1-ETO], inv(16) [CBFbeta-MYH11], MLL chimeric fusion genes, and cases classified as FAB-M7. When subsets of these genes were used in supervised learning algorithms, an overall classification accuracy of more than 93% was achieved. Moreover, we were able to use the expression signatures generated from the pediatric samples to accurately classify adult de novo AMLs with the same genetic lesions. The class discriminating genes also provided novel insights into the molecular pathobiology of these leukemias. Finally, using a combined pediatric data set of 130 AMLs and 137 acute lymphoblastic leukemias, we identified an expression signature for cases with MLL chimeric fusion genes irrespective of lineage. Surprisingly, AMLs containing partial tandem duplications of MLL failed to cluster with MLL chimeric fusion gene cases, suggesting a significant difference in their underlying mechanism of transformation.
Ross
Mary E
ME
Department of Hematology-Oncology, Hartwell Center for Bioinformatics and Biotechnology, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, TN 38105, USA.
Mahfouz
Rami
R
Onciu
Mihaela
M
Liu
Hsi-Che
HC
Zhou
Xiaodong
X
Song
Guangchun
G
Shurtleff
Sheila A
SA
Pounds
Stanley
S
Cheng
Cheng
C
Ma
Jing
J
Ribeiro
Raul C
RC
Rubnitz
Jeffrey E
JE
Girtman
Kevin
K
Williams
W Kent
WK
Raimondi
Susana C
SC
Liang
Der-Cherng
DC
Shih
Lee-Yung
LY
Pui
Ching-Hon
CH
Downing
James R
JR
D000328:Adult; D000465:Algorithms; D001769:Blood; D001853:Bone Marrow; D002648:Child; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification* / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics; D012307:Risk Factors; D020080:Tandem Repeat Sequences; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase