Computational Systems Biology Methods and Protocols.7z

chain reaction (PCR)/real-time PCR, genome/transcriptome

microarray technology, and next-generation sequencing

[11, 19]. Additionally, methods used in discovery steps for aberrant

genomic alterations can be totally different from those used in

clinical practice, mainly due to the cost efficiency, being time-

consuming, and easy operation. Some non-genomic techniques

have been also introduced to detect genomic prognostic factors,

such as flow cytometry [19].

Collectively, improvement for ALL treatment is a very good

example for translational medicine from basic genomic study to

clinical practice; we will demonstrate its history in three parts based

on the new genomic technologies that were introduced and illus-

trate the genetic variants of ALL identified in three eras of genetic

research (Fig.1).

2 Pregenome-Wide Investigation Era

2.1 Nongenomic
Diagnostic/Prognostic
Factors

It is much earlier for description of leukemia as a distinct disease

than introduction of genetic investigation into ALL classification.

Multiple interindividual differences have been firstly noticed for

several risk factors including age at diagnosis and ethnicity. For

instance, the incidence rates for ALL have a peak prevalence

between 2 and 5 years old and rank in the order of Hispanics,

Caucasians/Asians, and Africans according to the epidemiology

investigation [6]. With the use of microscope staining technique,

the classification of blood cells and the diagnosis of leukemia can be

determined by cytomorphologic and immunophenotypic features,

thus introducing diagnostic factors like leukocyte (or white blood

cell, WBC) count and immune lineage (separating B-lineage and

T-lineage ALL) [20]. Not surprisingly, the most important usage of

the diagnostic factors is not only for ALL diagnosis but also for its

ALL

Leukemogenesis

Germline Somatic alteration

Pre-genome wide era: CYP1A1, XRCC1, etc;E2A-PBX1, TEL-AML1, etc

Array-based genome wide:ARID5B,IKZF1, etc; PAX5/IKZF1 deleon, etc

NGS-based genome wide: ETV6, CDKN2A, etc; KRAS, NRAS, CREBBP-ZNF384, etc

Pre-genome wide era: BCR-ABL, hyperdiploidy, etc

Array-based genome wide:BCR-ABL-like, IKZF1deletion, etc;

NGS-based genome wide:NT5C2, PRPS1, etc;

Somac alteraon

Pre-genome wide era: TPMT, etc

Array-based genome wide:NUDT15, GRIN3A, etc;

NGS-based genome wide: NT5C2, PRPS1, etc;

Germline

Fig. 1Genetic alterations of ALL identified in different eras of genetic research

Insights of Acute Lymphoblastic Leukemia with Development of Genomic... 389