الفهرس 
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Abstract
Acute myeloid leukemia accounts for 1.45% of all cancers
and for 32% of newly diagnosed acute leukemia in Egypt.
Treatment of AML strategies needs to be developed by
identifying new markers and targets for treatment because about
50% of patients die due to aggressive disease and the percentage
of old patients that survive more than 5 years with this disease
is less than 10%. It is required to identify good molecular
markers that precisely characterize this disease
MUC4 gene expression is associated with poor outcomes in
many solid tumors including pancreatic, colon and stomach
cancers and is regarded as a prognostic factor in these tumors
and its high expression of MUC4 is regarded as one from the
important prognostic factors of chemotherapeutic failure in high
risk pediatric B-ALL.
LMWPTP (ACP1) gene overexpression was regarded as a
potential marker for primary stages of tumorigenesis. It is
overexpressed in many solid tumors as colon, prostate,
colorectal cancers and neuroblastoma and this overexpression is
accompanied by worse treatment outcome and low survival rate.
Also it is involved in the presence of chemoresistance
phenotype in CML and melanoma cancer.
Summary
96
Therefore, this study was designed to investigate the
expression levels of ACP1 and MUC4 genes in adult and
pediatric patients with AML, and evaluate their diagnostic and
prognostic values in this disease.
This study was conducted on 146 subjects recruited from
the adult and pediatric medical oncology department of the
National Cancer Institute, Cairo University from May 2016 to
May 2017. AML patients were fully diagnosed by clinical and
laboratory examinations before conducting the study. The
study was approved by the ethical committee, review board of
NCI, Cairo University in accordance with Helsinki guidelines
for the protection of human subjects. Written informed consent
was obtained from all subjects.
All participants in this study were divided into four groups;
(Ⅰ) Adult patients. (ⅠⅠ) Pediatric patients. (ⅠⅠⅠ) Adult healthy
control. (ⅠV) Pediatric healthy control.
All patients were routinely subjected to:
Full history and clinical examination.
Hematological and biochemical laboratory investigations
required for AML diagnosis (CBC, IPT, cytogenetic and
molecular study).
Defining the treatment response at Day 28 from starting 1
st
chemotherapy induction
Summary
97
Follow up was done after 1st induction period till death or
last visit or end of study in October 2019.
OS was measured from the date of entry into the study to
death or last visit and DFS was defined as the duration
from the date of CR achievement to death or relapse.
All subjects including patients and healthy donors were
evaluated for:
Quantitative gene expression analysis of MUC4 gene
compared to GAPDH as a reference gene using Real time
PCR.
Quantitative gene expression analysis of ACP1 gene
compared to GAPDH as a reference gene using Real time
PCR.
The results of the study can be summarized as follow:
BM expression level of MUC4 was significantly
overexpressed in adult and pediatric AML patients when
compared to the control group (p = 0.005, p<0.001
respectively).
For adults, MUC4 gene expression level in BM was
significantly associated with AML treatment response as its
expression level was lower in the persistent remission group
compared to the resistant or the relapse groups (p=0.001),
also good responders have high expression level of MUC4
Summary
98
in the good responders in comparison to the poor responders
to chemotherapy (p<0.001). For pediatric group, there was
no difference of BM MUC4 expression levels between good
and poor responders.
Kaplan-Meier test elucidated that shorter OS and DFS in
adults were significantly associated with high expression
levels of MUC4 in BM (p=0.011, p=0.006 respectively).
Univariate and multivariate Cox regression models assured
that there were significant relationships between shorter OS
and DFS with high expression levels of MUC4. High
expression levels of MUC4 can be regarded as an
independent prognostic factor for poorer OS and DFS in
adult AML patients. But in pediatrics, OS wasn’t associated
with MUC4 expression level.
There was no significant association between MUC4 levels
and sex, BM blasts, HB, PLT count, TLC, FLT3-ITD
mutation or karyotyping classification in adult and pediatric
patients. In pediatrics, older patients have overexpression of
MUC4 levels when compared to younger patients (p=0.032).
Expression levels of ACP1 was significantly increased in
AML patients (adult & pediatrics) when compared to
control.
Summary
99
No significant association was found between ACP1
expression level and treatment response or final outcome. In
addition, survival analysis by Kaplan-Meier test revealed
that ACP1 expression can’t be used to predict OS in AML
patients either for adults or pediatrics. DFS also wasn’t
associated with ACP1 expression in adults.
There was no significant association between ACP1 levels
and sex, age, BM blasts, HB, PLT count, TLC, FLT3-ITD
mutation or karyotyping classification.