Applications of DNA Microarray Technology in Cancer Research - DNA Microarray Technology and Data Analysis in Cancer Research - page 13

strongly suggests that DNA microarray technology may be used in the
diagnosis of human blood cancers, although the improvement to a 100%
prediction rate is the ultimate goal.
2.3. Our DNA Microarray Study Using Mouse Model
of BCR-ABL-Induced Leukemia
Here, we use our DNA microarray studies as examples to show our views
on how a microarray experiment should be designed and how the data
should be interpreted. To help explain the rationale of our study on
leukemia cells and the mouse leukemia model we used, we first introduce
some disease-related background information.
Human Philadelphia chromosome-positive (Ph + ) leukemias induced
by the BCR-ABL oncogene are among the most common hematologic
malignancies, and include chronic myeloid leukemia (CML) and B-cell
ALL (B-ALL). The BCR gene, on chromosome 22, breaks at either
exon 1, exon 12/13, or exon 19; and fuses to the c-ABL gene on chro-
mosome 9 to form, respectively, three types of BCR-ABL: P190, P210,
or P230. In humans, each of the three forms of the BCR-ABL oncogene
is associated with a distinct type of leukemia [see review by Advani and
Pendergast (2002)]. The P190 form is most often present in B-ALL, but
only rarely in CML. P210 is the predominate form in CML, and in some
acute lymphoid and myeloid leukemias in CML blast crisis. P230 was
recently found in a very mild form of CML (Pane et al ., 1996). CML has
a triphasic clinical course: a chronic phase, in which BCR-ABL-expressing
pluripotent stem cells massively expand but undergo normal differentia-
tion to form mature neutrophils; an accelerated phase, in which neutrophil
differentiation becomes progressively impaired and the cells become less
sensitive to myelosuppressive medications; and blast crisis, a condition
resembling acute leukemia in which myeloid or lymphoid blasts fail to
differentiate. The transition from chronic phase to blast crisis results from
additional genetic alterations, and this process is not well understood.
Lymphoid blast crisis of CML and Ph + B-ALL account for 20% of adults
and 5% of children afflicted with ALL. Among those patients, 50% of
adults and 20% of children carry P210BCR-ABL while the rest carry
P190BCR-ABL (Druker et al ., 2001a; Sawyers, 1999).