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AML M3 and AML M3 variant each have a distinct gene expression signature but also share patterns different from other genetically defined AML subtypes
Author(s) -
Haferlach Torsten,
Kohlmann Alexander,
Schnittger Susanne,
Dugas Martin,
Hiddemann Wolfgang,
Kern Wolfgang,
Schoch Claudia
Publication year - 2005
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20175
Subject(s) - biology , gene , phenotype , dna microarray , acute promyelocytic leukemia , gene expression , leukemia , genetics , microbiology and biotechnology , cancer research , retinoic acid
Acute promyelocytic leukemia (APL) with t(15;17) appears in two phenotypes: AML M3, with abnormal promyelocytes showing heavy granulation and bundles of Auer rods, and AML M3 variant (M3v), with non‐ or hypogranular cytoplasm and a bilobed nucleus. We investigated the global gene expression profiles of 35 APL patients (19 AML M3, 16 AML M3v) by using high‐density DNA‐oligonucleotide microarrays. First, an unsupervised approach clearly separated APL samples from other AMLs characterized genetically as t(8;21) ( n = 35), inv(16) ( n = 35), or t(11q23)/MLL ( n = 35) or as having a normal karyotype ( n = 50). Second, we found genes with functional relevance for blood coagulation that were differentially expressed between APL and other AMLs. Furthermore, a supervised pairwise comparison between M3 and M3v revealed differential expression of genes that encode for biological functions and pathways such as granulation and maturation of hematologic cells, explaining morphologic and clinical differences. Discrimination between M3 and M3v based on gene signatures showed a median classification accuracy of 90% by use of 10‐fold CV and support vector machines. Additional molecular mutations such as FLT3‐LM, which were significantly more frequent in M3v than in M3 ( P < 0.0001), may partly contribute to the different phenotypes. However, linear regression analysis demonstrated that genes differentially expressed between M3 and M3v did not correlate with FLT3‐LM. © 2005 Wiley‐Liss, Inc.