الفهرس 
coverOnly 14 pages are availabe for public view
 |  | from | 304 |  |  |
| | | from | 304 | | |
Abstract
Acute myeloid leukemia (AML) is characterized by
uncontrolled proliferation of hematopoietic progenitor cells,
blocked maturation resulting from interruption of normal
differentiation pathways, and activation of antiapoptotic
pathways.
Chemotherapy for leukemia frequently causes resistance
and side effects to patients. Therefore, development of
effective therapeutic treatment agents for leukemia is an
important and urgent topic.
Angiogenic induction was described in several
hematologic neoplasms such as acute and chronic leukemias,
myelodysplastic syndrome, and MM. The risk of active disease
in patients correlated positively with bone marrow micro-vascular (BM MVD).
Consistent with their biological functions, Ang-1 is
constitutively expressed throughout adult tissues providing a
stabilizing signal, while normal post-natal Ang-2 expression is
only observed at sites of active vascular remodeling.
Angiogenesis has become an attractive target for drug
therapy because of its key role in tumor growth. An extensive
array of compounds is currently in preclinical development,
with many now entering the clinic and/or achieving approval
from the US Food and Drug Administration. Several regulatory
and signaling molecules governing angiogenesis are of interest,
including growth factors (eg, vascular endothelial growth
factor, platelet-derived growth factor, fibroblast growth factor,
and epidermal growth factor), receptor tyrosine kinases, and
transcription factors such as hypoxia inducible factor, as well
as molecules involved in mitogen-activated protein kinase
(MAPK) and phosphoinositide 3-kinase (PI3K) signaling
Ang-2 is destabilizing factor that regulates vessel
remodeling under the influence of VEGF. It facilitates the
regression of vessels in the absence of VEGF but in their
presence, Ang-2 induced an angiogenic response which reveals
the interaction of Ang-2 and VEGF in tumor angiogenesis.
The present study aimed to evaluate angiopoietin-2 as a
marker of angiogenesis in patients with newly diagnosed acute
myeloid leukemia at presentation and after induction
chemotherapy and its correlation with other known prognostic
factors in an attempt to predict outcome of this disease for a
better understanding of the pathogenesis of AML which may
be translated as a targeted therapy.
The current study was carried in Ain Shams University
Hospitals, Clinical Hematology and Oncology Unit, on forty
(40) adult patients with newly diagnosed acute myeloid
leukemia, twenty patients (20/40) were females, while twenty
patients were males (20/40).
All of them were subjected to full history taking,
thorough physical examination, laboratory investigations
which included CBC, blood chemistry, radiological
investigations, as well as BM examination for morphological
assessment, Immunophenotyping by flow cytometry (FCM) on
BM aspirate and Quantitative detection of angiopoietin-2 in
the peripheral blood by Enzyme Linked Immuno-Sorbent
Assay (ELISA) at presentation and after induction
chemotherapy.
AML patients were diagnosed according to
morphological and immunophenotypic criteria according to
their positivity to myeloid markers into different FAB
subtypes.
In this study, the level of Ang-2 was higher at
presentation compared to its level after induction
chemotherapy therapy and there was a highly significant
correlation between them.
In the present study the Ang-2 with cutoff value
>390pg/dl-demonstrated high sensitivity (80%) but less
specificity (60%) in predicting survival.
There was no statistically significant association
between serum level of angiopoietin-2 at diagnosis and
patient’s sex and age.
Our data appeared to demonstrate that there was no
significant correlation between levels of Ang-2 and expression
of CD34.
Statistical analyses did not reveal any significant
differences between AML FAB subtypes.
Statistical analyses did not reveal any significant
differences between favorable, intermediate and unfavorable
groups as regard angiopoietin-2 level.
In the present study level of angiopoietin-2 was not
correlated with the percentage of the bone marrow blast or
peripheral blood blast at presentation and after induction
chemotherapy therapy.
In the present study there was no association between
angiopoietin-2 with WBC’s and LDH in AML patients at
diagnosis respectively.
In present study, patients with low levels of Ang-2 <
390pg/dl had long median survival time compared with
patients with high Ang-2 >390pg/dl, with statistically
significant correlation between low and high level of Ang-2 as
regarding to the survival time.
Moreover, there was statistically significant correlation
between high and low angiopoeitin-2 levels regarding to the
clinical outcome of AML patients between alive and dead
cases (P<0.05).
We found that there was a significant correlation
between angiopoietin-2 level and tumor volume
(splenomegaly), different FAB subtypes and cytogenetic risk
as poor adverse prognostic factors.
We demonstrated that there was statistically significant
correlation between outcome of all patients regarding to
gender, tumor burden (splenomegaly and lymphadenopathy),
platelet count, level of angiopoeitin-2.
Our study reported that an inverse relationship between
Ang-2 level and disease outcome in AML patients regarding
remission rate.