Identification of a gene expression signature associated with pediatric AML prognosis

Abstract

Most patients with acute myeloid leukemia (AML) enter complete remission (CR) after treatment with chemotherapy, but a large number of them experience relapse with resistant disease. To identify genes that are associated with their prognoses, we analyzed gene expression in 54 pediatric patients with AML using an oligonucleotide microarray that contained 12 566 probe sets. A supervised approach using the Student t test selected a prognostic set of 35 genes, some of which are associated with the regulation of cell cycle and apoptosis. Most of these genes had not previously been reported to be associated with prognosis and were not correlated with morphologically classified French-American-British (FAB) subtypes or with karyotypes. These results indicate the existence of prognosis-associated genes that are independent of cell lineage and cytogenetic abnormalities, and they can provide therapeutic direction for individual risk-adapted therapy for pediatric AML patients.

Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations

“…We have performed an extensive geneexpression analysis of childhood ALL and AML cases, normal bone marrows (NBMs), and purified normal hematopoietic subpopulations of different lineages and maturation stages. Using unsupervised analyses, we confirm and further extend previous findings showing that pediatric leukemias segregate based mainly on their lineage and primary genetic aberrations (8,9,14). Furthermore, we have identified genes that correlate with characteristic primary genetic changes and studied their expression patterns in different normal hematopoietic subpopulations.…”

“…So far, only a few large-scale gene-expression analyses of childhood leukemia have been reported, and none has included gene profiling data on normal hematopoietic cells of different maturation levels (8,9,14). We have performed an extensive geneexpression analysis of childhood ALL and AML cases, normal bone marrows (NBMs), and purified normal hematopoietic subpopulations of different lineages and maturation stages.…”

siRNA-mediated AML1/MTG8 depletion affects differentiation and proliferation-associated gene expression in t(8;21)-positive cell lines and primary AML blasts

“…One group consists of genes with expression levels typical for CBF leukaemias, including t(8;21)-positive AMLs. Application of AML1/MTG8 siRNA reduced the expression of those genes (BAALC, CBFA2T1, CD34, DUSP6) with an elevated expression in leukaemic cells, and increased transcript levels of those (ATP2B4, LAPTM5, LCP1) with diminished expression in blast cells (Yagi et al, 2003;Bullinger et al, 2004;Ross et al, 2004;Valk et al, 2004). A second group (CALR, CST7, HGF, IGFBP7, MEF2C, NKG7, PRG1 and RNASE3) contains genes with increased expression levels in t(15;17)-positive acute promyelocytic leukaemia (APL) or in mainly monocytic AMLs with 11q23 abnormalities (Table 5).…”

Targeting CDK6 in cancer: State of the art and new insights

“…[35][36][37] CDK6 is overexpressed in lymphoma, leukemia, glioma, glioblastoma, medulloblastoma, and cancers of squamous cells, salivary gland, bladder, pancreas and prostate. [38][39][40][41][42][43][44][45][46][47][48][49][50] In human prostate cancer cells, CDK6 has also been shown to bind androgen receptor and stimulate its activity in a kinase activity independent manner. 46 Blockage of CDK6 expression by microRNAs (miRNAs) has been shown to inhibit the proliferation of gliomas, medulloblastoma, prostate, bladder, gastric, hepatocellular, and lung cancer cells, indicating the significant role of CDK6 in the initiation and progression of these cancers.…”