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

Alessandra Trojani, Ester Pungolino, Giuseppe Rossi, Mariella D'Adda, Milena Lodola, Barbara Di Camillo, Alessandra Perego, Mauro Turrini, Ester Orlandi, Lorenza Borin, Alessandra Iurlo, Simona Malato, Francesco Spina, Maria Luisa Latargia, Francesco Lanza, Salvatore Artale, Michela Anghilieri, Maria Cristina Carraro, Gabriella De Canal, Enrica MorraRoberto Cairoli

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish
Pages (from-to)41-53
Number of pages13
JournalCancer Biomarkers
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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Leukemia, Myeloid, Chronic Phase
Gene Expression Profiling
Bone Marrow
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Therapeutics
Myeloproliferative Disorders
Sphingolipids
Platelet Activation
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Cell Adhesion
Protein-Tyrosine Kinases
Genes
Insulin Resistance
Cell Differentiation
Intercellular Signaling Peptides and Proteins
B-Lymphocytes
Apoptosis
Lipids
Glucose

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 journalArticle

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, ML, Lanza, F, Artale, S, Anghilieri, M, Carraro, MC, De Canal, G, Morra, E & Cairoli, R 2017, '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', Cancer Biomarkers, vol. 21, no. 1, pp. 41-53. https://doi.org/10.3233/CBM-170209
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. / 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. In: Cancer Biomarkers. 2017 ; Vol. 21, No. 1. pp. 41-53.
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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.",
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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

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DO - 10.3233/CBM-170209

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