الفهرس 
TitleOnly 14 pages are availabe for public view
 |  | from | 122 |  |  |
| | | from | 122 | | |
Abstract
Acute Myeloid Leukemia (AML) is a lethal hematologic malignancy. AML arises in
the context of a bone marrow microenvironment characterized by an immunosuppressive
milieu that fosters tumor growth and immune escape. Critical elements of this environment
include increased presence of accessory cells with an inhibitory phenotype that polarize
cells towards a tolerizing phenotype.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature
myeloid cells with potent immune suppressing activity. Increased presence of MDSCs is
associated with tumor progression, poor outcomes and decreased effectiveness of
immunotherapeutic strategies.
MDSCs are characterized by the expression of the myeloid markers CD11b and
CD33 and absent HLA-DR. Two distinct subsets have been further characterized,
monocytic MDSCs, with the phenotype CD15- and granulocytic MDSCs, who are CD15+.
While both subtypes have been identified in healthy patients, levels are increased in
patients with solid malignancies as well as hematologic malignancies.
MUC1is a uniquely important oncoprotein critically involved in the self- renewal,
cell proliferation and resistance to apoptosis of leukemic cells. While previous reports
suggest that MUC1 signaling may exert immunosuppressive effects, the nature and
mechanism mediating this effect has not be fully elucidated.
The present work aimed at the study of myeloid derived suppressor cells level and
Mucin1 gene expression in de novo AML, its relation with disease characteristics and response
to induction chemotherapy. The initial diagnosis was based on history taking, family history,
full clinical examination, laboratory tests including CBC, chemistry and bone marrow
examination. Follow up CBC and bone marrow examination were performed at day 28
post induction chemotherapy.
The present study was conducted on 50 newly diagnosed non-M3 adult AML
patients and 10 healthy controls attending at Hematology department- MRI - Alexandria
University, MDSCs were significantly higher in AML patients mean value of 8.11 ±
8.02% compared to normal controls mean value was 0.42 ± 0.20. Also, MDSCs showed
significant correlation with blast % in peripheral blood, bone marrow and WBCs count.
While there was no significant correlation regarding AML FAB subtypes and blast
phenotype with MDSCs level.
MDSCs showed negative significant correlation regarding response to induction
chemotherapy at day 28 where patients achieving CR1 had significantly lower myeloid
derived suppressor cells level compared to those achieving PR. Also, patients achieving
CR1 had significantly lower myeloid derived suppressor cells level compared to
nonresponsive patients as well as patients who died. Also, one year survival for AML
patients showed significant negative correlation with MDSCs level.
Summary, Conclusion and Recommendations
90
MUC1 gene expression showed significantly higher level in AML patients with a median
value of 8.80 (3.57 – 18.82) compared to normal controls. MUC1 over expression didn’t
correlate with either FAB classification or other measured parameters, including clinical and
laboratory parameters. As regards response to induction chemotherapy, there was no statistical
significance between MUC1 gene expression and response to induction chemotherapy.
6.2. Conclusion
The present study highlighted the role of MDSCs and MUC1 in AML patients:
1. Both MDSCs and MUC1 play an important role in AML pathogenesis and
contribute to tumor related immune suppression.
2. MDSCs are expanded in the presence of AML blasts which are present in peripheral
as well as bone marrow.
3. MDSCs level testing is easy to use and test results are available for reporting within
2–3 h.
4. MDSCs can be used as an early predictor for response to therapy. Also, it can be
used as a prognostic tool in AML.
5. Peripheral blood samples can be used in evaluating MDSCs level.
6. MUC1 gene expression level is up regulated in AML patients.
7. MUC1 gene expression level has no significant correlation as regard response to
induction chemotherapy and one year survival in AML patients.
6.3. Recommendations
1. It is recommended to evaluate MDSCs level at diagnosis as well as after treatment.
2. It is recommended to use additional markers to evaluate MDSCs in HLADR
negative AML patients.
3. Evaluation of both monocytic and granulocytic subtypes of MDSCs in AML
patients is recommended.
4. It is recommended to study MDSCs and MUC1 gene expression in AML patients
with different molecular and genetic aberrations.
5. Further studies are recommended to use MDSCs and MUC1 as a therapeutic target
in AML patients.
6. A larger sample size is recommended in further studies.