An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.

Blood
Klaus H MetzelerGerman AML Cooperative Group

Abstract

Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P = .002), event-free survival (HR = 1.73; P = .001), and relapse-free survival (HR = 1.76; P = .025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR = 4.11; P < .001), event-free survival (HR = 2.90; P < .001), and relapse-free survival (HR = 3.14, P < .001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene-expression signature that offers additional prognostic in...Continue Reading

References

May 1, 1990·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·B D ChesonM J Keating
Mar 13, 1999·Annals of Internal Medicine·A C JusticeJ A Berlin
Jul 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Claudia SchochTorsten Haferlach
Jan 2, 2003·Journal of the National Cancer Institute·Richard SimonLisa M McShane
Mar 11, 2004·Blood Reviews·Krzysztof MrózekClara D Bloomfield
Apr 16, 2004·The New England Journal of Medicine·Lars BullingerJonathan R Pollack
Apr 16, 2004·The New England Journal of Medicine·Peter J M ValkRuud Delwel
Apr 20, 2004·PLoS Biology·Eric Bair, Robert Tibshirani
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
Jan 22, 2005·The New England Journal of Medicine·Brunangelo FaliniUNKNOWN GIMEMA Acute Leukemia Working Party
May 10, 2005·Blood·Torsten HaferlachClaudia Schoch
Nov 9, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Guido MarcucciClara D Bloomfield
May 3, 2008·The New England Journal of Medicine·Richard F SchlenkUNKNOWN German-Austrian Acute Myeloid Leukemia Study Group
May 3, 2008·The New England Journal of Medicine·Guido MarcucciClara D Bloomfield

❮ Previous
Next ❯

Citations

Apr 29, 2010·Current Hematologic Malignancy Reports·Guido MarcucciClara D Bloomfield
Jul 19, 2012·Current Oncology Reports·Raya Mawad, Elihu H Estey
Feb 27, 2013·Medical Oncology·Nuzhat N KabirJulhash U Kazi
Jul 26, 2012·Blood Cancer Journal·Z PašaliçS K Bohlander
Mar 30, 2011·Leukemia·K Theilgaard-MönchL Bullinger
Jul 10, 2010·Nature Medicine·Michael G KharasGeorge Q Daley
Aug 30, 2011·Nature Medicine·Kolja EppertJohn E Dick
Dec 13, 2012·Molecular & Cellular Proteomics : MCP·Francesco BonardiJan Jacob Schuringa
Jan 30, 2013·The Journal of Experimental Medicine·Camille LobryIannis Aifantis
Jan 20, 2011·Briefings in Bioinformatics·Anne-Laure Boulesteix, Willi Sauerbrei
May 27, 2009·Current Opinion in Hematology·Krzysztof MrózekGuido Marcucci
Apr 8, 2010·Science Translational Medicine·Yoriko SaitoFumihiko Ishikawa
Apr 28, 2009·BMC Medical Genomics·Hideaki MizunoAkinori Sarai
Jul 31, 2013·Genome Medicine·Gabriel M AltschulerWinston A Hide
May 14, 2010·PLoS Computational Biology·Markus RiesterFranziska Michor
Nov 8, 2011·Haematologica·Arnaud PetitVirginie Penard-Lacronique
Jul 4, 2012·International Journal of Environmental Research and Public Health·Julia E Rager, Rebecca C Fry
Apr 7, 2015·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Edison OngGiovanni Paternostro
Feb 4, 2014·Nature Genetics·Bryan ZimdahlTannishtha Reya
Aug 10, 2013·EMBO Molecular Medicine·Jung Eun ParkQi Zeng
Mar 25, 2014·Current Hematologic Malignancy Reports·Bhavana Bhatnagar, Ramiro Garzon
Oct 30, 2014·BMC Medical Research Methodology·Riccardo De BinAnne-Laure Boulesteix
Feb 6, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Zejuan LiJianjun Chen
Apr 22, 2009·Expert Review of Molecular Diagnostics·Andrea Staratschek-JoxJoachim L Schultze
Nov 26, 2010·Expert Review of Hematology·Karen W L Yee, Armand Keating
Jun 6, 2015·International Journal of Molecular Medicine·Zhiming DingQiang Ding
Nov 29, 2011·Clinics in Laboratory Medicine·Jennifer J D Morrissette, Adam Bagg
Mar 23, 2011·Seminars in Oncology·Lucy A GodleyMichelle M Le Beau
Dec 5, 2009·The Journal of Molecular Diagnostics : JMD·Margaret L GulleyYuri Fedoriw
Aug 25, 2009·Best Practice & Research. Clinical Haematology·Ulrike BacherTorsten Haferlach

❮ Previous
Next ❯

Related Concepts

Related Feeds

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Acute Myeloid Leukaemia & RNA

Acute myeloid leukaemia (AML) is a common hematological type of cancer. As the population ages, there has been a rise in the frequency of AML. RNA expression has been used to see if there are different genetic profiles that exist within AML and whether these may underpin the variations in survival rates. Here is the latest research on AML and RNA.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.