whole TMPT genes by using Sanger sequencing [33]. This finding
has been successfully translated into clinical practice for dosage
adjustment of mercaptopurine (e.g., disease ~10-fold in patients
with homozygous-inactiveTPMTSNPs) and remarked as one of
the most useful pharmacogenetic markers [34].
Collectively, through the low-throughput techniques in the
pre-genome-wide investigation era, most of the frequent abnormal
diploid and translations in leukemia cells have been identified and
largely improved the classifications of ALL and the following indi-
vidualized treatment. These techniques (e.g., FISH) are still used in
clinical determinations of ALL subtypes because of their high effi-
ciency of cost and time on identifications of limited known
alterations.3 Array-Based Genome-Wide Investigation Era
3.1 Microarray
Investigation
The “cDNA microarray” was firstly developed to detect expression
of more than 1000 genes simultaneously in the 1990s [35]. This
technology has been largely improved and well established by a few
companies including Affymetrix and Illumina, which can detect up
to 50 thousand genes accurately, and is still popularly used in the
study of cancer genomics up to now. “DNA microarray” is mainly
used for two purposes: genome-wide investigation of somatic copy
number alterations (CNAs) (also for germline copy number varia-
tions in some studies) [36] and genotypes of up to two millions
germline single nucleotide polymorphisms (SNPs) [37]. Multiple
versions of DNA and cDNA microarrays have been used for explor-
ing the unknown cancer-related alterations which can’t be identi-
fied by the traditional techniques due to the high throughput and
resolution of microarrays. This technology consists of the syntheses
of nucleic acids at high density on the solid support and allows to
investigate thousands of unique nucleic acid fragments simulta-
neously to genome-widely detect gene expression with
RNA/cDNA templates or SNP genotypes and copy number varia-
tion with DNA templates [38, 39].
To perform a microarray analysis, nucleic acid molecules will be
fragmented and labeled with fluorescent probe; scanning of the
microarray will proceed after hybridization in the microarray slide
[35, 40]. Expression level, SNP genotypes, and copy number var-
iations can be detected and normalized in a relatively unbiased
procedure through bioinformatics analyses afterward [41]. With
the development of technology, quantified alternative splicing can
be detected by exon-based cDNA microarray [42], while SNP and
CNV/CNA detections have been interrogated by using a single
DNA microarray (e.g., Affymetrix SNP 6.0 [43]). Different plat-
forms only vary in the nature of the probes used and genomic
resolution [44]. Normally, in order to get the informative signalsInsights of Acute Lymphoblastic Leukemia with Development of Genomic... 393