Abstract
BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin-cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib.
| Original language | English |
|---|---|
| Pages (from-to) | 41-53 |
| Number of pages | 13 |
| Journal | Cancer Biomarkers |
| Volume | 21 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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Keywords
- bone marrow CD34+/lin-cells
- CML
- GEP
- nilotinib
ASJC Scopus subject areas
- Oncology
- Genetics
- Cancer Research
Cite this
Wide-transcriptome analysis and cellularity of bone marrow CD34+/lin- cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs. 12 months of first-line nilotinib treatment. / Trojani, Alessandra; Pungolino, Ester; Rossi, Giuseppe; D'Adda, Mariella; Lodola, Milena; Di Camillo, Barbara; Perego, Alessandra; Turrini, Mauro; Orlandi, Ester; Borin, Lorenza; Iurlo, Alessandra; Malato, Simona; Spina, Francesco; Latargia, Maria Luisa; Lanza, Francesco; Artale, Salvatore; Anghilieri, Michela; Carraro, Maria Cristina; De Canal, Gabriella; Morra, Enrica; Cairoli, Roberto.
In: Cancer Biomarkers, Vol. 21, No. 1, 01.01.2017, p. 41-53.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Wide-transcriptome analysis and cellularity of bone marrow CD34+/lin- cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs. 12 months of first-line nilotinib treatment
AU - Trojani, Alessandra
AU - Pungolino, Ester
AU - Rossi, Giuseppe
AU - D'Adda, Mariella
AU - Lodola, Milena
AU - Di Camillo, Barbara
AU - Perego, Alessandra
AU - Turrini, Mauro
AU - Orlandi, Ester
AU - Borin, Lorenza
AU - Iurlo, Alessandra
AU - Malato, Simona
AU - Spina, Francesco
AU - Latargia, Maria Luisa
AU - Lanza, Francesco
AU - Artale, Salvatore
AU - Anghilieri, Michela
AU - Carraro, Maria Cristina
AU - De Canal, Gabriella
AU - Morra, Enrica
AU - Cairoli, Roberto
PY - 2017/1/1
Y1 - 2017/1/1
N2 - BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin-cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib.
AB - BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin-cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib.
KW - bone marrow CD34+/lin-cells
KW - CML
KW - GEP
KW - nilotinib
UR - http://www.scopus.com/inward/record.url?scp=85038859397&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038859397&partnerID=8YFLogxK
U2 - 10.3233/CBM-170209
DO - 10.3233/CBM-170209
M3 - Article
AN - SCOPUS:85038859397
VL - 21
SP - 41
EP - 53
JO - Cancer Biomarkers
JF - Cancer Biomarkers
SN - 1574-0153
IS - 1
ER -