scholarly journals Gene expression profiling of acute myeloid leukemia samples from adult patients with AML-M1 and -M2 through boutique microarrays, real-time PCR and droplet digital PCR

2017 ◽  
Author(s):  
Luiza Handschuh ◽  
Maciej Kaźmierczak ◽  
Marek Milewski ◽  
Michał G�ralski ◽  
Magdalena Łuczak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Gene Expression Profiling ◽  
Real Time ◽  
Real Time Pcr ◽  
Expression Profiling ◽  
Myeloid Leukemia ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Acute Myeloid

Differences of Somatic Mutations and Gene Expression in Blasts of Transient Leukemia and Acute Myeloid Leukemia of Down Syndrome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2364-2364
Author(s):  
Jian Chen ◽  
Fouad Yousif ◽  
Timothy Beck ◽  
John D McPherson ◽  
Johann K. Hitzler
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Down Syndrome ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Transient Leukemia ◽  
Genetic Events ◽  
Acute Myeloid

Abstract Background: Transient leukemia (TL) occurs in 30% of newborns with Down syndrome (DS) and typically resolves spontaneously. Approximately 20% of infants with TL go on to develop acute myeloid leukemia of DS (DS-AML) within the first four years of life. The blasts of both TL and DS-AML harbor somatic mutations of GATA1 . The objective of this study was to identify additional genetic events, which associated with the progression of TL to DS-AML. Methods: Leukemic blasts of TL, DS-AML and normal T lymphocytes were sorted from blood and bone marrow samples of five patients who successively developed both disorders. In addition, blasts of one patient with subsequent relapse of DS-AML were analyzed. Mutational spectrum and gene expression and were determined by exome sequencing and RNASeq (Illumina HiSeq2000). The presence of mutations, which were identified with this approach in DS-AML blasts, was examined by droplet digital PCR in TL blasts (BioRad QX200). Results: Blasts of TL overall harbored fewer mutations than those of DS-AML. Mutations of cohesin and RAS pathway genes were identified in a subset of DS-AML but not TL. In the patient who developed a relapse, different cohesin gene mutations were detected at initial diagnosis of AML and relapse; a minor clone present at initial diagnosis of AML emerged as the predominant clone at relapse. Concordant somatic GATA1 mutations were present in both TL and DS-AML blasts derived from the same patient. In contrast, other genetic events, which were detected in DS-AML blasts by exome sequencing, were confirmed to be absent in TL (by droplet digital PCR). The majority of differentially expressed genes showed higher expression levels in blasts of TL compared to DS-AML. They included genes encoding chemokines and related to IL1 and TGFb signaling. Conclusions: The pathogenic sequence starting with TL and culminating in AML is uniquely initiated in children with DS by somatic mutation of GATA1. In contrast, the events associated with the transformation of TL to DS-AML resemble progression factors also found in non-DS AML. These progression events were not detectable even in minor subclones of TL suggesting they are acquired after the onset of TL. This research was supported by funding from the Canadian Cancer Society Research Institute and Ontario Institute for Cancer Research. Disclosures No relevant conflicts of interest to declare.

scholarly journals Integrated genome-wide genotyping and gene expression profiling reveals BCL11B as a putative oncogene in acute myeloid leukemia with 14q32 aberrations

Haematologica ◽  
2014 ◽  
Vol 99 (5) ◽  
pp. 848-857 ◽  
Author(s):  
S. Abbas ◽  
M. A. Sanders ◽  
A. Zeilemaker ◽  
W. M. C. Geertsma-Kleinekoort ◽  
J. E. Koenders ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Myeloid Leukemia ◽  
Genome Wide ◽  
Acute Myeloid

Use of Gene-Expression Profiling to Identify Prognostic Subclasses in Adult Acute Myeloid Leukemia

2004 ◽  
Vol 350 (16) ◽  
pp. 1605-1616 ◽  
Author(s):  
Lars Bullinger ◽  
Konstanze Döhner ◽  
Eric Bair ◽  
Stefan Fröhling ◽  
Richard F. Schlenk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Myeloid Leukemia ◽  
Acute Myeloid

Gene expression profiling of minimally differentiated acute myeloid leukemia: M0 is a distinct entity subdivided by RUNX1 mutation status

Blood ◽  
2009 ◽  
Vol 114 (14) ◽  
pp. 3001-3007 ◽  
Author(s):  
Fernando P. G. Silva ◽  
Sigrid M. A. Swagemakers ◽  
Claudia Erpelinck-Verschueren ◽  
Bas J. Wouters ◽  
Ruud Delwel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Myeloid Leukemia ◽  
Loss Of Function ◽  
Transcription Regulators ◽  
Runx1 Mutation ◽  
Acute Myeloid

Minimally differentiated acute myeloid leukemia (AML-M0) is defined by immature morphology and expression of early hematologic markers. By gene expression profiling (GEP) and subsequent unsupervised analysis of 35 AML-M0 samples and 253 previously reported AML cases, we demonstrate that AML-M0 cases express a unique signature that is largely separated from other molecular subtypes. Hematologic transcription regulators such as CEBPA, CEBPD, and ETV6, and the differentiation associated gene MPO appeared strongly down-regulated, in line with the primitive state of this leukemia. AML-M0 frequently carries loss-of-function RUNX1 mutation. Unsupervised analyses revealed a subdivision between AML-M0 cases with and without RUNX1 mutations. RUNX1 mutant AML-M0 samples showed a distinct up-regulation of B cell–related genes such as members of the B-cell receptor complex, transcription regulators RUNX3, ETS2, IRF8, or PRDM1, and major histocompatibility complex class II genes. Importantly, prediction with high accuracy of the AML-M0 subtype and prediction of patients carrying RUNX1 mutation within this subtype were possible based on the expression level of only a few transcripts. We propose that RUNX1 mutations in this AML subgroup cause lineage infidelity, leading to aberrant coexpression of myeloid and B-lymphoid genes. Furthermore, our results imply that AML-M0, although originally determined by morphology, constitutes a leukemia subgroup.

Gene Expression Profiling in Acute Myeloid Leukemia

2005 ◽  
Vol 23 (26) ◽  
pp. 6296-6305 ◽  
Author(s):  
Lars Bullinger ◽  
Peter J.M. Valk
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Myeloid Leukemia ◽  
Molecular Taxonomy ◽  
Detailed Knowledge ◽  
New Information ◽  
Therapeutic Decision Making ◽  
Acute Myeloid

Over the last decades, significant advances have been made in the knowledge and treatment of acute myeloid leukemia (AML). The WHO has recognized this new information by incorporating into its classification morphologic, immunophenotypic, genetic, and clinical features in an attempt to define biologically and clinically relevant entities. Nevertheless, well-defined cytogenetic subgroups exhibit considerable heterogeneity, and in many AML subtypes the pathogenic event is still not known. A classification system based on the underlying molecular pathogenetic abnormalities would be ideal, but such detailed knowledge is not yet available. Novel approaches in genomics, such as surveying the expression levels of thousands of genes in parallel using DNA microarray technology, open possibilities to further refine the studies on AML. Today, gene expression profiling in AML is becoming well established and has already been proven to be valuable in diagnosing different cytogenetic subtypes, discovering novel AML subclasses, and predicting clinical outcome. Recently, gene expression profiling studies in AML showed a remarkable level of concordance in findings, which may ultimately lead to an increasingly refined molecular taxonomy. While many challenges remain to be overcome, a combination of gene expression profiling with other microarray-based applications, high-throughput mutational analyses and proteomic approaches will not only significantly contribute to the classification and therapeutic decision making of AML, but also give important insights into the true pathobiologic nature of this type of leukemia.

Sign in / Sign up

Export Citation Format

Share Document