1. 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
- Author
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Salvatore Artale, Gabriella De Canal, Enrica Morra, Maria Cristina Carraro, Giuseppe Rossi, Simona Malato, Alessandra Perego, Maria Luisa Latargia, Mariella D'Adda, Francesco Lanza, Ester Orlandi, Francesco Spina, Barbara Di Camillo, Alessandra Iurlo, Mauro Turrini, Michela Anghilieri, Roberto Cairoli, Milena Lodola, Alessandra Trojani, Lorenza Borin, Ester Pungolino, 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, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, and Cairoli, R
- Subjects
Myeloid ,0301 basic medicine ,Cancer Research ,Time Factors ,CD34 ,Antigens, CD34 ,Transcriptome ,Leukocyte Count ,0302 clinical medicine ,hemic and lymphatic diseases ,CML ,Leukemic ,Leukemia ,Gene Expression Regulation, Leukemic ,Myeloid leukemia ,General Medicine ,Protein-Tyrosine Kinases ,GEP ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Leukemia, Myeloid, Chronic-Phase ,bone marrow CD34+/lin-cell ,medicine.drug ,bone marrow CD34+/lin-cells ,Bone Marrow Cells ,NO ,03 medical and health sciences ,Genetics ,medicine ,Humans ,Antigens ,nilotinib ,business.industry ,Gene Expression Profiling ,medicine.disease ,Gene expression profiling ,Pyrimidines ,030104 developmental biology ,Gene Expression Regulation ,Nilotinib ,Cancer research ,Chronic-Phase ,Bone marrow ,business - 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.
- Published
- 2017