daunorubicin) and higher risk of relapse than other subtypes, which
is similar as that for BCR-ABL1 positive patients [68]. However,
some of the BCR-ABL1-like patients are sensitive to tyrosine kinase
inhibitors (e.g., imatinib) although they don’t have the BCR-ABL1
translations. In this case, a newly defined molecular subtype with
high risk can be detected by transcriptome profiling and exhibits as
a prognostic factor for high risk. BCR-ABL1-like patients are also
treated with a specific clinical regimen to increase their survival
time. For T-ALL, a subtype has also been observed initially by
immunophenotype, which is similar to that of early thymic pro-
genitors (ETP) and has a poor treatment outcome. Besides the
aberrant expression of CD1A, CD5, and CD8, ETP T-ALL cases
have distinct gene expression signatures and exhibit signals of
myeloid and stem cell markers [70, 71].
On the other hand, genome-wide detection of expression for
leukemia samples with altered drug sensitivity can also identify the
candidate genes or gene pathways for treatment outcomes, espe-
cially drug resistance. For instance, significantly higher expression
of CASP1 has been noticed in glucocorticoid-resistant leukemia
cells through transcriptome profile screening for leukemia cells
from more than 4000 ALL patients. Subsequent mechanism stud-
ies indicate that overexpression of CASP1 resulted in cleavage of
the glucocorticoid receptor, diminished the glucocorticoid-
induced transcriptional response, and increased glucocorticoid
resistance [72].3.4 Genomic
Profiling for Leukemia
Cells
Several microarray-based techniques for the genome-wide analysis
of DNA CNA have been well established for cancer genomic stud-
ies, especially for ALL [37, 73]. Most ALL samples have relatively
fewer alterations than many solid tumors [74] and tend to be focal
and limited to one or a few genes, indicating that ALL is not
characterized by gross genomic instability [61, 66]. More than
50 genetic regions have been noticed to have recurrent CNAs in
ALL patients, containing genes with known or putative roles in
lymphoid development or leukemogenesis/tumorigenesis [9, 44,
61 ], including well-reported tumor suppressors (e.g.,CDKN2A/
CDKN2B and RB1), lymphoid development regulators (e.g.,
PAX5and IKZF1), and even some rare drug response-related
genes (e.g.,NR3C1)[75]. Interestingly, the frequency of these
alterations is also significantly associated with the presence of chro-
mosomal alterations [9, 61].
As the most common CNAs in all types of cancers, large or
focal deletion ofCDKN2A/CDKN2Bis also frequently observed
in ALL, especially T-ALL [61]. Similar to other solid cancers, loss
of three proteins coded by these two genes (i.e., p14 and p16 for
CDKN2Aand p15 forCDKN2B), can impact multiple regulatory
pathways and induce uncontrolled check of cell cycle, apoptosis
escape, and etc. Thus, alteration of this region is considered to396 Heng Xu and Yang Shu