Genome-wide analysis of acute myeloid leukemia with normal karyotype reveals a unique pattern of homeobox gene expression distinct from those with translocation-mediated fusion events.
Gene expression profiles were determined from presentation peripheral blood and bone marrow samples of 28 patients with acute myeloid leukemia (AML). Hierarchical clustering sorted the profiles into separate groups, each representing one of the major cytogenetic classes in AML [i.e., t(8;21), t(15;17), inv(16), 11q23, and normal karyotype]. Statistical group comparison identified genes whose expression was strongly correlated with these chromosomal classes. Moreover, the normal karyotype AMLs were characterized by distinctive up-regulation of certain members of the class I homeobox A and B gene families, implying a common underlying genetic lesion. These data reveal novel diagnostic and therapeutic targets and demonstrate the potential of microarray-based dissection of AML.
Debernardi
Silvana
S
Cancer Research UK, Medical Oncology Unit, Barts and the Royal London School of Medicine and Dentistry, London, United Kingdom.
Lillington
Debra M
DM
Chaplin
Tracy
T
Tomlinson
Simon
S
Amess
John
J
Rohatiner
Ama
A
Lister
T Andrew
TA
Young
Bryan D
BD
D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000737:chemistry / Q000473:pathology; D002648:Child; D016000:Cluster Analysis; D020732:Cytogenetic Analysis / Q000145:classification / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D007621:Karyotyping / Q000379:methods; D007951:Leukemia, Myeloid / Q000097:blood / Q000145:classification / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000145:classification / Q000235:genetics; D015479:Leukemia, Myelomonocytic, Acute / Q000097:blood / Q000145:classification / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000145:classification / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D014178:Translocation, Genetic / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm