MATRIX METALLOPROTEINASES 2 & 9 AND TISSUE INHIBITOR OF MATRIX METALLOPROTEINASE 1 AS MAJOR PLAYERS IN CLINICAL COURSE OF EGYPTIAN PEDIATERIC ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS
(Abstract release date: 05/19/16)
EHA Library. AlSaleh M. 06/09/16; 134521; PB1621
Dr. Mahasen AlSaleh
Contributions
Contributions
Abstract
Abstract: PB1621
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is the most frequent acute leukemia affecting pediatric patients. Gelatinase B/matrix metalloproteinase -9 (MMP9) as well as MMP-2 (gelatinase-A) and their inhibtor Tissue inhibitor of matrix metalloproteinases (TIMP)-1 play a crucial role modulating the biology of the cancer stem cell niche.
Aims
Study the impact of expression of MMP2, MMP9 and TIMP1, as well as, MMP2/TIMP1 and MMP9/TIMP1 ratios on different facets of disease progression in pediatric ALL in terms of laboratory and clinical parameters having prognostic significance, disease-free and overall survival .
Methods
Bone marrow samples were drawn from 53 Egyptian pediatric ALL patients presented to Pediatric Oncology Department, National Cancer Institute, Cairo University. An informed consent in accordance with the Declaration of Helsinki was obtained. Intracytoplasmic MMP-9 FITC, MMP-2 PE and TIMP-1 FITC was done. MoAbs were supplied from R&D system(614 McKinley Place NE, Minneapolis, MN 55413) analysis was done within 24 hours of sampling. Sample analysis was done by multicolor flow cytometry (Coulter Epics XL, Hialeah, USA). Gating strategy was applied using dim CD45/side scatter. Data analysis was done on Winlist 6 (Verity Software House, Topsham, ME)
Results
The study included 53 pediatric ALL patients, 34 males and 19 females, age ranged from 1-18 year with a median of 6 years. A significantly higher total leukocyte count (TLC) among TIMP-1 positive ALL cases and a borderline significantly higher TLC among MMP9 positive ones (P=0.03 and 0.06, respectively) were found. As regards clinical parameters, hepatomegaly was higher among MMP-9 positive cases (P=0.03). Regarding the relation of MMP2 and MMP9 in to their inhibitor; MMP2/TIMP1 ratio was significantly correlated to MMP9/TIMP1 ratio (p<0.001).ROC curve using MMP2/TIMP2 ratio as greater than or equal to 0.02 will detect MRD D42 response (negative or <0.01) with a sensitivity of 73.7%, specificity of 72.7%, positive predictive value 82.4% and negative predictive value of 61.5%. A low MMP2/TIMP1 ratio correlated significantly with presence of splenomegaly (p<0.02). Patients with MMP2/TIMP1 ratio < 2.0% had shorter overall survival with mean 48± 3.4 months as compared to those with ratios ≥2.0% (p=0.04).
Conclusion
MMP2, MMP9, TIMP1expression as well as, MMP2/TIMP1 and MMP9/TIMP1 ratios had influential implication on disease progression and clinical course on pediatric acute lymphoblastic leukemia.
Session topic: E-poster
Keyword(s): ALL, MMP, TIMP 1
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is the most frequent acute leukemia affecting pediatric patients. Gelatinase B/matrix metalloproteinase -9 (MMP9) as well as MMP-2 (gelatinase-A) and their inhibtor Tissue inhibitor of matrix metalloproteinases (TIMP)-1 play a crucial role modulating the biology of the cancer stem cell niche.
Aims
Study the impact of expression of MMP2, MMP9 and TIMP1, as well as, MMP2/TIMP1 and MMP9/TIMP1 ratios on different facets of disease progression in pediatric ALL in terms of laboratory and clinical parameters having prognostic significance, disease-free and overall survival .
Methods
Bone marrow samples were drawn from 53 Egyptian pediatric ALL patients presented to Pediatric Oncology Department, National Cancer Institute, Cairo University. An informed consent in accordance with the Declaration of Helsinki was obtained. Intracytoplasmic MMP-9 FITC, MMP-2 PE and TIMP-1 FITC was done. MoAbs were supplied from R&D system(614 McKinley Place NE, Minneapolis, MN 55413) analysis was done within 24 hours of sampling. Sample analysis was done by multicolor flow cytometry (Coulter Epics XL, Hialeah, USA). Gating strategy was applied using dim CD45/side scatter. Data analysis was done on Winlist 6 (Verity Software House, Topsham, ME)
Results
The study included 53 pediatric ALL patients, 34 males and 19 females, age ranged from 1-18 year with a median of 6 years. A significantly higher total leukocyte count (TLC) among TIMP-1 positive ALL cases and a borderline significantly higher TLC among MMP9 positive ones (P=0.03 and 0.06, respectively) were found. As regards clinical parameters, hepatomegaly was higher among MMP-9 positive cases (P=0.03). Regarding the relation of MMP2 and MMP9 in to their inhibitor; MMP2/TIMP1 ratio was significantly correlated to MMP9/TIMP1 ratio (p<0.001).ROC curve using MMP2/TIMP2 ratio as greater than or equal to 0.02 will detect MRD D42 response (negative or <0.01) with a sensitivity of 73.7%, specificity of 72.7%, positive predictive value 82.4% and negative predictive value of 61.5%. A low MMP2/TIMP1 ratio correlated significantly with presence of splenomegaly (p<0.02). Patients with MMP2/TIMP1 ratio < 2.0% had shorter overall survival with mean 48± 3.4 months as compared to those with ratios ≥2.0% (p=0.04).
Conclusion
MMP2, MMP9, TIMP1expression as well as, MMP2/TIMP1 and MMP9/TIMP1 ratios had influential implication on disease progression and clinical course on pediatric acute lymphoblastic leukemia.
Session topic: E-poster
Keyword(s): ALL, MMP, TIMP 1
Abstract: PB1621
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is the most frequent acute leukemia affecting pediatric patients. Gelatinase B/matrix metalloproteinase -9 (MMP9) as well as MMP-2 (gelatinase-A) and their inhibtor Tissue inhibitor of matrix metalloproteinases (TIMP)-1 play a crucial role modulating the biology of the cancer stem cell niche.
Aims
Study the impact of expression of MMP2, MMP9 and TIMP1, as well as, MMP2/TIMP1 and MMP9/TIMP1 ratios on different facets of disease progression in pediatric ALL in terms of laboratory and clinical parameters having prognostic significance, disease-free and overall survival .
Methods
Bone marrow samples were drawn from 53 Egyptian pediatric ALL patients presented to Pediatric Oncology Department, National Cancer Institute, Cairo University. An informed consent in accordance with the Declaration of Helsinki was obtained. Intracytoplasmic MMP-9 FITC, MMP-2 PE and TIMP-1 FITC was done. MoAbs were supplied from R&D system(614 McKinley Place NE, Minneapolis, MN 55413) analysis was done within 24 hours of sampling. Sample analysis was done by multicolor flow cytometry (Coulter Epics XL, Hialeah, USA). Gating strategy was applied using dim CD45/side scatter. Data analysis was done on Winlist 6 (Verity Software House, Topsham, ME)
Results
The study included 53 pediatric ALL patients, 34 males and 19 females, age ranged from 1-18 year with a median of 6 years. A significantly higher total leukocyte count (TLC) among TIMP-1 positive ALL cases and a borderline significantly higher TLC among MMP9 positive ones (P=0.03 and 0.06, respectively) were found. As regards clinical parameters, hepatomegaly was higher among MMP-9 positive cases (P=0.03). Regarding the relation of MMP2 and MMP9 in to their inhibitor; MMP2/TIMP1 ratio was significantly correlated to MMP9/TIMP1 ratio (p<0.001).ROC curve using MMP2/TIMP2 ratio as greater than or equal to 0.02 will detect MRD D42 response (negative or <0.01) with a sensitivity of 73.7%, specificity of 72.7%, positive predictive value 82.4% and negative predictive value of 61.5%. A low MMP2/TIMP1 ratio correlated significantly with presence of splenomegaly (p<0.02). Patients with MMP2/TIMP1 ratio < 2.0% had shorter overall survival with mean 48± 3.4 months as compared to those with ratios ≥2.0% (p=0.04).
Conclusion
MMP2, MMP9, TIMP1expression as well as, MMP2/TIMP1 and MMP9/TIMP1 ratios had influential implication on disease progression and clinical course on pediatric acute lymphoblastic leukemia.
Session topic: E-poster
Keyword(s): ALL, MMP, TIMP 1
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is the most frequent acute leukemia affecting pediatric patients. Gelatinase B/matrix metalloproteinase -9 (MMP9) as well as MMP-2 (gelatinase-A) and their inhibtor Tissue inhibitor of matrix metalloproteinases (TIMP)-1 play a crucial role modulating the biology of the cancer stem cell niche.
Aims
Study the impact of expression of MMP2, MMP9 and TIMP1, as well as, MMP2/TIMP1 and MMP9/TIMP1 ratios on different facets of disease progression in pediatric ALL in terms of laboratory and clinical parameters having prognostic significance, disease-free and overall survival .
Methods
Bone marrow samples were drawn from 53 Egyptian pediatric ALL patients presented to Pediatric Oncology Department, National Cancer Institute, Cairo University. An informed consent in accordance with the Declaration of Helsinki was obtained. Intracytoplasmic MMP-9 FITC, MMP-2 PE and TIMP-1 FITC was done. MoAbs were supplied from R&D system(614 McKinley Place NE, Minneapolis, MN 55413) analysis was done within 24 hours of sampling. Sample analysis was done by multicolor flow cytometry (Coulter Epics XL, Hialeah, USA). Gating strategy was applied using dim CD45/side scatter. Data analysis was done on Winlist 6 (Verity Software House, Topsham, ME)
Results
The study included 53 pediatric ALL patients, 34 males and 19 females, age ranged from 1-18 year with a median of 6 years. A significantly higher total leukocyte count (TLC) among TIMP-1 positive ALL cases and a borderline significantly higher TLC among MMP9 positive ones (P=0.03 and 0.06, respectively) were found. As regards clinical parameters, hepatomegaly was higher among MMP-9 positive cases (P=0.03). Regarding the relation of MMP2 and MMP9 in to their inhibitor; MMP2/TIMP1 ratio was significantly correlated to MMP9/TIMP1 ratio (p<0.001).ROC curve using MMP2/TIMP2 ratio as greater than or equal to 0.02 will detect MRD D42 response (negative or <0.01) with a sensitivity of 73.7%, specificity of 72.7%, positive predictive value 82.4% and negative predictive value of 61.5%. A low MMP2/TIMP1 ratio correlated significantly with presence of splenomegaly (p<0.02). Patients with MMP2/TIMP1 ratio < 2.0% had shorter overall survival with mean 48± 3.4 months as compared to those with ratios ≥2.0% (p=0.04).
Conclusion
MMP2, MMP9, TIMP1expression as well as, MMP2/TIMP1 and MMP9/TIMP1 ratios had influential implication on disease progression and clinical course on pediatric acute lymphoblastic leukemia.
Session topic: E-poster
Keyword(s): ALL, MMP, TIMP 1
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