Research done by Research done by Dr. Jackleen Raafat Awadallah Hanna Phd of Medical Biochemistry Researcher at Medical Biochemistry Department National Research Center Egypt Under the Supervision of Prof. Dr. Maged A. Barakat Prof. Dr. Zakaria A. El-Khayat Professor of Biochemistry Professor of Biochemistry Faculty of Pharmacy Medical Biochemistry Department Cairo University National Research Center Dr. Manal F. Ismail Ass. Professor of Biochemistry
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Research done by Dr. Jackleen Raafat Awadallah Hanna Phd of Medical Biochemistry Researcher at Medical Biochemistry Department National Research Center.
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Research done by Research done by
Dr. Jackleen Raafat Awadallah HannaPhd of Medical Biochemistry
Researcher at Medical Biochemistry DepartmentNational Research Center
Egypt
Under the Supervision of
Prof. Dr. Maged A. Barakat Prof. Dr. Zakaria A. El-Khayat Professor of Biochemistry Professor of Biochemistry Faculty of Pharmacy Medical Biochemistry Department Cairo University National Research Center
Dr. Manal F. IsmailAss. Professor of Biochemistry
Faculty of Pharmacy Cairo University
Expression of CD95 in Acute Lymphocytic Leukemia (ALL) in Egyptian Children before and
after Treatment
Leukemia
It’s is the term used for cancer that affects the blood cells.
Marrow-based neoplasm composed predominantly of minimally or partially differentiated lymphoid precursors.
The malignant disorder resulting from the clonal proliferation of lymphoid precursors with arrested maturation is known as
It is the most common type of Leukemia found in children that's why it is commonly called childhood leukemia.
Apoptosis
(Programmed cell death)
Controlled cellular self-destruction.
Regulation of normal cell growth is balanced between cell proliferation, cell differentiation and apoptosis, a disruption of this balance is thought to be an important event leading to carcinogenesis. Apoptosis induction is the target of most chemotheropeutic drugs.
Regulation of apoptosis
Pro- apoptotic protein.
CD95
(Fas, Apo-1)
Cross linking of Fas by its ligand (Fas L)
Apoptosis
Bcl-2
It is located within the mitochondrial membrane, endoplasmic reticulum and nuclear envelope.
Bcl-2 family of proteins :- Bax , Bcl-2
Treatment protocol for childhood ALL
The induction phase (6-7 weeks)
The consolidation phase(8 weeks)
HD-MTX , 6-MP
DEX, VCR, DOX, 6-MP, ASP, Ith, MTX, Cyclo, Ara-C.
VCR, DOX, Prednisone, Ara C,6-MP,Cyclo, ASP Ith (MTX, Ara C, hydrocortisone)The maintenance phase
(120 weeks)
Total XV (Pui et al., 2004)
Zinc Copper
Zinc is found in almost every cell of the body.
It forms complexes with metalloenzymes with oxidase activity. It stimulates the
activity of approximately 100 enzymes.
Nutritional status of children with ALL
Aim of the workIdentify the changes occurring in newly diagnosed ALL children regarding the expression of CD95
receptor and blood level of Bcl-2 as markers of apoptosis as well as serum zinc and copper levels prior to and during the maintenance phase of the specified treatment protocol.
Subjects
Group 1 Group 3Group 2
Ten normal healthy children
Twenty five pediatric patients newly diagnosed
of acute lymphocytic
leukemia
Twenty treated patients
Routine laboratory investigations
Complete blood count
(CBC)
Hemoglobin concentration
Bone marrow
blast count
Total leukocyte count
Platelet count
Sampling
Determination of CD95 % using
Flowcytometer Determination of Bcl-2
Concentration using ELISA
Blood
Determination of zinc and copper
levels using
atomic absorption spectrophotometer
Serum
Hemoglobin concentration in groups 1,2 and 3.
a
a,b
0
2
4
6
8
10
12
14
Hem
og
lob
in (
gm
%)
Group1
Group2
Group3
Platelet count (Plts) in groups 1,2 and 3.
aa,b
0
100
200
300P
lts.*
(10)
3 (c
u.m
m.)
Group1
Group2
Group3
Bone marrow blast count (B.M.blast) in groups 1,2 and 3.
aa,b
0
20
40
60
80
100
B.M
.bla
st %
Group1
Group2
Group3
Total Leukocytic count (TLC) in groups 1,2 and 3.
a
b0
50
100
150
200
250
TL
C *
(10)3
(cu
.mm
.)
Group1
Group2
Group3
CD95 % in groups 1,2 and 3.
a
a,b
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7C
D95 % Group1
Group2
Group3
Bcl-2 concentration in groups 1,2 and 3.
a
a,b
0
100
200
300
400
500
600
700
800
Bcl-
2 (
pg
/ml)
Group1
Group2
Group3
Serum Cu levels in groups 1,2 and 3.
a a
0
100
200
300
400
Cu (u
g/dl
)
Group1
Group2
Group3
Serum Zn levels in groups 1,2 and 3.
a
b
0
50
100
150
Zn (u
g/dl
) Group1
Group2
Group3
Cu/Zn in groups 1,2 and 3.
a
a,b
0
1
2
3
4
5
6
Cu
/Zn Group1
Group2
Group3
0.00 200.00 400.00 600.00 800.00 1000.00
Bcl2
0.00
0.20
0.40
0.60
0.80
1.00
CD
95
R Sq Linear = 0.618
40.00 60.00 80.00 100.00 120.00
Zn
100.00
150.00
200.00
250.00
300.00
350.00
400.00
Cu
R Sq Linear = 0.514
The current study demonstrated that both CD95 % and Bcl-2 protein are useful diagnostic markers that may help not only in diagnosis but also in follow up of ALL cases.
Long-term studies with large number of cases are still needed.
Avoiding chronic zinc deficiency should be taken into consideration in the prevention of childhood leukemia.