Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in pediatric Acute Lymphoblastic Leukemia Elixabet López-López, Ángela Gutierrez-Camino, Idoia Martín-Guerrero, M Ángeles Piñán, Nagore García de Andoin, Aurora Navajas, Purificación García-Miguel, Javier Ballesteros, África García- Orad 1
28
Embed
Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in pediatric Acute Lymphoblastic Leukemia Elixabet López-López, Ángela Gutierrez-Camino,
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in
pediatric Acute Lymphoblastic Leukemia
Elixabet López-López, Ángela Gutierrez-Camino, Idoia Martín-Guerrero, M Ángeles Piñán, Nagore García de Andoin, Aurora Navajas, Purificación
García-Miguel, Javier Ballesteros, África García-Orad
1
Acute Lymphoblastic Leukemia
Most common pediatric malignancy
Disorder of the lymphoblastsAccumulation of blast cells in BM and PB
IntroductionIntroduction
Normal
ALL
2
Survival 10% 80%
Risk groups characterization
Well-established treatment protocols directed to risk groups
IntroductionIntroduction
3
DNR VCR
PDN CFM
ASP TIT (MTX)
MTX 6MP
AraC TIT (MTX)
VCR PDN ASP
MTX 6MP
CFM TIT (MTX)
epiADR VCR
DEXA CFM
MTX ASP
AraC TIT (MTX)
VCR PDN
MTX 6MP
TIT (MTX)
VCR DNR
DEXA CFM
MTX ASP
AraC TIT (MTX)
Induction Consolidation
Intensification
Maintenance
HR
VHR
Induction
Induction
Consolidation
Consolidation Blocks Intensification
Maintenance
Graft
MTX 6MP
AraC TIT (MTX)
MTX 6MP
AraC TIT (MTX)
DNR VCR
PDN CFM
ASP TIT (MTX)
DNR VCR
PDN CFM
ASP TIT (MTX)
IntroductionIntroduction
SR
4
LAL/SHOP protocol
DNR VCR
PDN CFM
ASP TIT (MTX)
MTX 6MP
AraC TIT (MTX)
VCR PDN ASP
MTX 6MP
CFM TIT (MTX)
epiADR VCR
DEXA CFM
MTX ASP
AraC TIT (MTX)
VCR PDN
MTX 6MP
TIT (MTX)
VCR DNR
DEXA CFM
MTX ASP
AraC TIT (MTX)
Induction Consolidation
Intensification
Maintenance
HR
VHR
Induction
Induction
Consolidation
Consolidation Blocks Intensification
Maintenance
Graft
MTX 6MP
AraC TIT (MTX)
MTX 6MP
AraC TIT (MTX)
DNR VCR
PDN CFM
ASP TIT (MTX)
DNR VCR
PDN CFM
ASP TIT (MTX)
IntroductionIntroduction
SR
5
LAL/SHOP protocol
DNR VCR
PDN CFM
ASP TIT (MTX)
MTX 6MP
AraC TIT (MTX)
VCR PDN ASP
MTX 6MP
CFM TIT (MTX)
epiADR VCR
DEXA CFM
MTX ASP
AraC TIT (MTX)
VCR PDN
MTX 6MP
TIT (MTX)
VCR DNR
DEXA CFM
MTX ASP
AraC TIT (MTX)
Induction Consolidation
Intensification
Maintenance
HR
VHR
Induction
Induction
Consolidation
Consolidation Blocks Intensification
Maintenance
Graft
MTX 6MP
AraC TIT (MTX)
MTX 6MP
AraC TIT (MTX)
DNR VCR
PDN CFM
ASP TIT (MTX)
DNR VCR
PDN CFM
ASP TIT (MTX)
IntroductionIntroduction
SR
6
Toxicity- Requires treatment reduction
LAL/SHOP protocol
DNR VCR
PDN CFM
ASP TIT (MTX)
MTX 6MP
AraC TIT (MTX)
VCR PDN ASP
MTX 6MP
CFM TIT (MTX)
epiADR VCR
DEXA CFM
MTX ASP
AraC TIT (MTX)
VCR PDN
MTX 6MP
TIT (MTX)
VCR DNR
DEXA CFM
MTX ASP
AraC TIT (MTX)
Induction Consolidation
Intensification
Maintenance
HR
VHR
Induction
Induction
Consolidation
Consolidation Blocks Intensification
Maintenance
Graft
MTX 6MP
AraC TIT (MTX)
MTX 6MP
AraC TIT (MTX)
DNR VCR
PDN CFM
ASP TIT (MTX)
DNR VCR
PDN CFM
ASP TIT (MTX)
IntroductionIntroduction
SR
7
Toxicity- Requires treatment reduction
PREDICTIVE MARKERS
LAL/SHOP protocol
IntroductionIntroduction
ABCB1
ABCG2ABCC2
MTX MTXSLCO1A2
ABCC3ABCC2
ABCC4
SLC22A6 SLC22A8
SLC19A1
SLCO1B3
ABCC1ABCG2
LIVER CELL
KIDNEY CELL
Elimination
Elimination
Via bileVia bloodstream
SLCO1B1
8
384 SNPs151 B-ALLLAL/SHOP
Gene SNP Allele OR (CI 95%) p Function
ABCC4 rs9516519 C 0.17 (0.05-0.5) 0.0003086(0.0188)
Putative miRNA binding site
ABCC2 rs3740065 C 3.75 (1.6-8.79) 0.002009(0.0340) Putative intronic enhancer
9
E. Lopez-Lopez et al. Pharmacogenetics and Genomics 2013
IntroductionIntroduction
Gene SNP Allele OR (CI 95%) p Function
ABCC4 rs9516519 C 0.17 (0.05-0.5) 0.0003086(0.0188)
Putative miRNA binding site
ABCC2 rs3740065 C 3.75 (1.6-8.79) 0.002009(0.0340) Putative intronic enhancer
10
E. Lopez-Lopez et al. Pharmacogenetics and Genomics 2013
IntroductionIntroduction
Gene SNP Allele OR (CI 95%) p Function
ABCC4 rs9516519 C 0.17 (0.05-0.5) 0.0003086(0.0188)
Putative miRNA binding site
ABCC2 rs3740065 C 3.75 (1.6-8.79) 0.002009(0.0340) Putative intronic enhancer
11
E. Lopez-Lopez et al. Pharmacogenetics and Genomics 2013
IntroductionIntroduction
Gene SNP Allele OR (CI 95%) p Function
ABCC4 rs9516519 C 0.17 (0.05-0.5) 0.0003086(0.0188)
Putative miRNA binding site
ABCC2 rs3740065 C 3.75 (1.6-8.79) 0.002009(0.0340) Putative intronic enhancer
12
E. Lopez-Lopez et al. Pharmacogenetics and Genomics 2013
IntroductionIntroduction
ABCB1
ABCG2
SLCO1A2
ABCC3
SLC22A6 SLC22A8
SLC19A1
SLCO1B3
ABCC1ABCG2
LIVER CELL
KIDNEY CELL
Via bile
Via bloodstream
SLCO1B1
ABCC2
MTX MTX
ABCC2
ABCC4Elimination
Elimination
MicroRNAs
1-BINDING
13
IntroductionIntroduction
MicroRNAs
IntroductionIntroduction
1-BINDING
2-LEVEL
14
MicroRNAs
IntroductionIntroduction
1-BINDING
2-LEVEL
15Adapted from Ryan et al, 2010
MicroRNAs
IntroductionIntroduction
1-BINDING
2-LEVEL
16Adapted from Ryan et al, 2010
To detect new toxicity markers in pediatric B-ALL patients studying miRNA-related polymorphisms