Identification of signature genes by microarray for acute myeloid leukemia without maturation and acute promyelocytic leukemia with t(15;17)(q22;q12)(PML/RARα)

Abstract

Acute myeloid leukemia (AML) has distinct subgroups characterized by different maturation and specific chromosomal translocation. In order to gain insight into the gene expression activities in AML, we carried out a gene expression profiling study with 21 AML samples using cDNA microarrays, focusing on acute promyelocytic leukemia with specific translocation t(15;17)(q22;q12) [French-American-British or FAB-M3 with t(15;17)] and AML without maturation (FAB-M1) characterized by morphologically and phenotypically immature AML blasts and no recurrent chromosomal abnormalities. Using a multivariate σ-classifier algorithm, we identified 33 strong feature genes that distinguish FAB-M3 with t(15;17) from other AML samples, and 24 strong feature genes that classify FAB-M1. A direct comparison between FAB-M3 with t(15;17) and FAB-M1 led to selection of 13 strong feature genes. Those genes include some known to be related to leukemogenesis and cell differentiation. RIN1, a gene in the ras pathway, was up-regulated in FAB-M3 with t(15;17). Growth factor-binding protein 2 gene was downregulated in FAB-M1. Huntingtin gene was up-regulated in FAB-M1. Others include syndecan 4, interleukin-2 receptor ß, folate receptor ß, low affinity immunoglobulin Á, Fc receptor IIC precursor, insulin-like growth factor binding protein 2, and myeloperoxidase, which are involved in cell differentiation. Overexpression of myeloperoxidase in FAB-M3 cells with t(15;17) compared to FAB-M1 cells is consistent with the conventional cytochemical staining pattern. Thus, the study revealed that a morphologically-defined FAB-M1 subtype has a distinct gene expression signature that contributes to its cell differentiation and proliferation as well as FAB-M3 with a recurrent cytogenetic abnormality t(15;17)(q22;q12).

Noninvasive Detection of Candidate Molecular Biomarkers in Subjects with a History of Insulin Resistance and Colorectal Adenomas

“…As opposed to using expression levels of either significantly increased or decreased genes, we applied novel mRNA-based noninvasive methods to identify the best single genes and two- to three-gene combinations for distinguishing polyps, IR, and exposure to a chemoprotective legume-enriched diet. Similar to previous studies (20, 21, 32, 49), we report that by using combinations of genes, the classification error rate can be significantly lowered. Two- and three-gene combinations thus provide robust classifiers with potential to noninvasively identify discriminative molecular signatures for differential diagnostic purposes.…”

Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction

“…A number of laboratories using supervised learning algorithms have identified unique gene expression signatures associated with karyotypic abnormalities, normal karyotypes, and NPM1 mutation status. [31][32][33][34][35][36][37][38][39] In contrast, we wished to determine whether gene expression profiling using an entirely unsupervised approach could reveal intrinsic biologic groups of AML among a set of wellcharacterized older AML patients, with a high frequency of normal and unfavorable cytogenetic abnormalities. We further wished to determine whether the gene expression signatures we derived were useful in risk classification and therapeutic targeting in this poor-risk disease.…”

Leucémies aiguës myéloïdes en Tunisie: caractéristiques épidémiologiques et cliniques et classification OMS

“…La translocation t(15;17) (q22;q21) est pré-sente dans 8,5 % des LAM : il s'agit dans tous les cas de leucémie aiguë promyélocytaire : dix cas de la forme hypergranulaire (LAM 3/FAB), douze cas de la forme variante microgranulaire (M3v), deux cas de LAM 3 avec blastes basophiles dans le sang (M3/M3v) et un cas de la forme basophile diagnostiqué initialement comme LAM 1 (Tableau 3). En effet, plus de 90 % des patients atteints de LAM 3 (FAB) ont la translocation spécifique t(15;17) (q22;q21) [29]. L'inversion du 16 est retrouvée dans quatre cas (1,4 %) : un cas de LAM 4 et trois cas de LAM 4 Eo (LAM avec composante monocytaire associée à une maturation éosinophile) (Tableau 3).…”