EVALUATION OF WNT AND HEDGEHOG SIGNALING PATHWAYS IN PEDIATRIC B ACUTE LYMPHOBLASTIC LEUKEMIA - A PRELIMINARY STUDY
(Abstract release date: 05/19/16)
EHA Library. Coucelo M. 06/09/16; 134499; PB1599
Dr. Margarida Coucelo
Contributions
Contributions
Abstract
Abstract: PB1599
Type: Publication Only
Background
Deregulation of signaling pathways such as Wingless (Wnt) and Hedghehog (Hh) that participate in normal hematopoietic stem-cell self-renewal, differentiation and proliferation have been implied in the leukemogenic process.
Aims
Our goal was to establish the activation patterns of Wnt and Hh signaling pathways in pediatric B-ALL patients in order to identify novel prognostic markers and new targets for therapeutic strategies.
Methods
We studied 9 bone marrow samples from pediatric patients with B-ALL, 8 at diagnosis and 1 at relapse (average age 10,2y, 4F:5M). Seven B-ALL had no recurrent genetic alterations (group 1, n=6), including the relapsed patient (group 2, n=1), and 2 B-ALL had a t(4;11) (MLL-AF4) (group 3, n=2). Three bone marrow samples without neoplastic disease were used as controls (average age 9y, 3F). All samples were submitted to a gene expression array that included 84 genes for each signaling pathway, Wnt (RT2 Profiler PCR Array, Qiagen) and Hh (Hedgehog Signaling Pathway, Biorad). Results were analyzed by RT2 Profiler PCR Array Data Analysis v3.5 (Qiagen) and considered statistically significant when p ≤0,05.
Results
In B-ALL patients Wnt signaling pathway genes were tendentiously downregulated. Group 1, comparing with control group, showed downregulation of WNT (WNT1/2B/5B/6/7A/7B/10A/10B/16) (p≤0,05) and FZD (FZD4/5/7/9) (p≤0,05) family genes, Wnt negative regulators (DKK3,KREMEN1,SFRP4) (p≤0,05) and cell cycle target genes (CCND1,RHOU)(p≤0,05). Group 3, when compared with group 1 revealed upregulation of WNT (WNT1,WNT10B) (p≤0,05), FZD (FZD3,FZD5,FZD9) (p≤0,05), negatives regulators (WIF1, KREMEN1) (p≤0,05)and target genes WISP1 and FOSL1 (p≤0,05). B-ALL patients at relapse, when compared with the other groups, showed a tendency for Wnt upregulation, including LEF-1.Hh signaling pathway results were more heterogeneous. Group 1, comparing to controls, presented a downregulation of some ligands (SHH) and receptors genes (PTCHD1,BOC,LRP2) (p<0,05) and upregulation of others (CDON,PTCHD2,RAB23) (p<0,05), with downregulation of some important Hh regulators and target genes (GLI2,ZIC2,FGF9,OTX2,GREM1,SFRP1,VEGFA)(p<0,05) and upregulation of others (CSNK1E, BCL2,p<0,05). Both, group 3 and the B-ALL patient at relapse, showed a tendency for downregulation of Hh ligands, target genes and transcription factors, when compared to group 1.
Conclusion
Our results, although very preliminary, suggest that B-ALL pediatric patients with no recurrent genetic alterations tend to present downregulation of Wnt signaling pathway genes and abnormal expression of Hh signaling pathway. Present results suggest that these pathways may provide novel prognostic markers and therapeutic targets, and are currently being validated in a larger patient cohort.
Session topic: E-poster
Keyword(s): Leukemia, Pediatric, Signaling, Wnt
Type: Publication Only
Background
Deregulation of signaling pathways such as Wingless (Wnt) and Hedghehog (Hh) that participate in normal hematopoietic stem-cell self-renewal, differentiation and proliferation have been implied in the leukemogenic process.
Aims
Our goal was to establish the activation patterns of Wnt and Hh signaling pathways in pediatric B-ALL patients in order to identify novel prognostic markers and new targets for therapeutic strategies.
Methods
We studied 9 bone marrow samples from pediatric patients with B-ALL, 8 at diagnosis and 1 at relapse (average age 10,2y, 4F:5M). Seven B-ALL had no recurrent genetic alterations (group 1, n=6), including the relapsed patient (group 2, n=1), and 2 B-ALL had a t(4;11) (MLL-AF4) (group 3, n=2). Three bone marrow samples without neoplastic disease were used as controls (average age 9y, 3F). All samples were submitted to a gene expression array that included 84 genes for each signaling pathway, Wnt (RT2 Profiler PCR Array, Qiagen) and Hh (Hedgehog Signaling Pathway, Biorad). Results were analyzed by RT2 Profiler PCR Array Data Analysis v3.5 (Qiagen) and considered statistically significant when p ≤0,05.
Results
In B-ALL patients Wnt signaling pathway genes were tendentiously downregulated. Group 1, comparing with control group, showed downregulation of WNT (WNT1/2B/5B/6/7A/7B/10A/10B/16) (p≤0,05) and FZD (FZD4/5/7/9) (p≤0,05) family genes, Wnt negative regulators (DKK3,KREMEN1,SFRP4) (p≤0,05) and cell cycle target genes (CCND1,RHOU)(p≤0,05). Group 3, when compared with group 1 revealed upregulation of WNT (WNT1,WNT10B) (p≤0,05), FZD (FZD3,FZD5,FZD9) (p≤0,05), negatives regulators (WIF1, KREMEN1) (p≤0,05)and target genes WISP1 and FOSL1 (p≤0,05). B-ALL patients at relapse, when compared with the other groups, showed a tendency for Wnt upregulation, including LEF-1.Hh signaling pathway results were more heterogeneous. Group 1, comparing to controls, presented a downregulation of some ligands (SHH) and receptors genes (PTCHD1,BOC,LRP2) (p<0,05) and upregulation of others (CDON,PTCHD2,RAB23) (p<0,05), with downregulation of some important Hh regulators and target genes (GLI2,ZIC2,FGF9,OTX2,GREM1,SFRP1,VEGFA)(p<0,05) and upregulation of others (CSNK1E, BCL2,p<0,05). Both, group 3 and the B-ALL patient at relapse, showed a tendency for downregulation of Hh ligands, target genes and transcription factors, when compared to group 1.
Conclusion
Our results, although very preliminary, suggest that B-ALL pediatric patients with no recurrent genetic alterations tend to present downregulation of Wnt signaling pathway genes and abnormal expression of Hh signaling pathway. Present results suggest that these pathways may provide novel prognostic markers and therapeutic targets, and are currently being validated in a larger patient cohort.
Session topic: E-poster
Keyword(s): Leukemia, Pediatric, Signaling, Wnt
Abstract: PB1599
Type: Publication Only
Background
Deregulation of signaling pathways such as Wingless (Wnt) and Hedghehog (Hh) that participate in normal hematopoietic stem-cell self-renewal, differentiation and proliferation have been implied in the leukemogenic process.
Aims
Our goal was to establish the activation patterns of Wnt and Hh signaling pathways in pediatric B-ALL patients in order to identify novel prognostic markers and new targets for therapeutic strategies.
Methods
We studied 9 bone marrow samples from pediatric patients with B-ALL, 8 at diagnosis and 1 at relapse (average age 10,2y, 4F:5M). Seven B-ALL had no recurrent genetic alterations (group 1, n=6), including the relapsed patient (group 2, n=1), and 2 B-ALL had a t(4;11) (MLL-AF4) (group 3, n=2). Three bone marrow samples without neoplastic disease were used as controls (average age 9y, 3F). All samples were submitted to a gene expression array that included 84 genes for each signaling pathway, Wnt (RT2 Profiler PCR Array, Qiagen) and Hh (Hedgehog Signaling Pathway, Biorad). Results were analyzed by RT2 Profiler PCR Array Data Analysis v3.5 (Qiagen) and considered statistically significant when p ≤0,05.
Results
In B-ALL patients Wnt signaling pathway genes were tendentiously downregulated. Group 1, comparing with control group, showed downregulation of WNT (WNT1/2B/5B/6/7A/7B/10A/10B/16) (p≤0,05) and FZD (FZD4/5/7/9) (p≤0,05) family genes, Wnt negative regulators (DKK3,KREMEN1,SFRP4) (p≤0,05) and cell cycle target genes (CCND1,RHOU)(p≤0,05). Group 3, when compared with group 1 revealed upregulation of WNT (WNT1,WNT10B) (p≤0,05), FZD (FZD3,FZD5,FZD9) (p≤0,05), negatives regulators (WIF1, KREMEN1) (p≤0,05)and target genes WISP1 and FOSL1 (p≤0,05). B-ALL patients at relapse, when compared with the other groups, showed a tendency for Wnt upregulation, including LEF-1.Hh signaling pathway results were more heterogeneous. Group 1, comparing to controls, presented a downregulation of some ligands (SHH) and receptors genes (PTCHD1,BOC,LRP2) (p<0,05) and upregulation of others (CDON,PTCHD2,RAB23) (p<0,05), with downregulation of some important Hh regulators and target genes (GLI2,ZIC2,FGF9,OTX2,GREM1,SFRP1,VEGFA)(p<0,05) and upregulation of others (CSNK1E, BCL2,p<0,05). Both, group 3 and the B-ALL patient at relapse, showed a tendency for downregulation of Hh ligands, target genes and transcription factors, when compared to group 1.
Conclusion
Our results, although very preliminary, suggest that B-ALL pediatric patients with no recurrent genetic alterations tend to present downregulation of Wnt signaling pathway genes and abnormal expression of Hh signaling pathway. Present results suggest that these pathways may provide novel prognostic markers and therapeutic targets, and are currently being validated in a larger patient cohort.
Session topic: E-poster
Keyword(s): Leukemia, Pediatric, Signaling, Wnt
Type: Publication Only
Background
Deregulation of signaling pathways such as Wingless (Wnt) and Hedghehog (Hh) that participate in normal hematopoietic stem-cell self-renewal, differentiation and proliferation have been implied in the leukemogenic process.
Aims
Our goal was to establish the activation patterns of Wnt and Hh signaling pathways in pediatric B-ALL patients in order to identify novel prognostic markers and new targets for therapeutic strategies.
Methods
We studied 9 bone marrow samples from pediatric patients with B-ALL, 8 at diagnosis and 1 at relapse (average age 10,2y, 4F:5M). Seven B-ALL had no recurrent genetic alterations (group 1, n=6), including the relapsed patient (group 2, n=1), and 2 B-ALL had a t(4;11) (MLL-AF4) (group 3, n=2). Three bone marrow samples without neoplastic disease were used as controls (average age 9y, 3F). All samples were submitted to a gene expression array that included 84 genes for each signaling pathway, Wnt (RT2 Profiler PCR Array, Qiagen) and Hh (Hedgehog Signaling Pathway, Biorad). Results were analyzed by RT2 Profiler PCR Array Data Analysis v3.5 (Qiagen) and considered statistically significant when p ≤0,05.
Results
In B-ALL patients Wnt signaling pathway genes were tendentiously downregulated. Group 1, comparing with control group, showed downregulation of WNT (WNT1/2B/5B/6/7A/7B/10A/10B/16) (p≤0,05) and FZD (FZD4/5/7/9) (p≤0,05) family genes, Wnt negative regulators (DKK3,KREMEN1,SFRP4) (p≤0,05) and cell cycle target genes (CCND1,RHOU)(p≤0,05). Group 3, when compared with group 1 revealed upregulation of WNT (WNT1,WNT10B) (p≤0,05), FZD (FZD3,FZD5,FZD9) (p≤0,05), negatives regulators (WIF1, KREMEN1) (p≤0,05)and target genes WISP1 and FOSL1 (p≤0,05). B-ALL patients at relapse, when compared with the other groups, showed a tendency for Wnt upregulation, including LEF-1.Hh signaling pathway results were more heterogeneous. Group 1, comparing to controls, presented a downregulation of some ligands (SHH) and receptors genes (PTCHD1,BOC,LRP2) (p<0,05) and upregulation of others (CDON,PTCHD2,RAB23) (p<0,05), with downregulation of some important Hh regulators and target genes (GLI2,ZIC2,FGF9,OTX2,GREM1,SFRP1,VEGFA)(p<0,05) and upregulation of others (CSNK1E, BCL2,p<0,05). Both, group 3 and the B-ALL patient at relapse, showed a tendency for downregulation of Hh ligands, target genes and transcription factors, when compared to group 1.
Conclusion
Our results, although very preliminary, suggest that B-ALL pediatric patients with no recurrent genetic alterations tend to present downregulation of Wnt signaling pathway genes and abnormal expression of Hh signaling pathway. Present results suggest that these pathways may provide novel prognostic markers and therapeutic targets, and are currently being validated in a larger patient cohort.
Session topic: E-poster
Keyword(s): Leukemia, Pediatric, Signaling, Wnt
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