ABSTRACT
BACKGROUND: Acute lymphoblastic leukemia (ALL) occurs in both adults and children but the response to chemotherapy and survival is significantly worse in the adults. We aimed to study whether the expression of immune system-associated miRNAs would differ between adult and pediatric patients with ALL at the time of diagnosis. MATERIALS AND METHODS: Inflammation-associated miRNA analysis was performed in 19 adults and 79 pediatric patients with ALL and involved miR-10, miR-15, miR-16, miR-17-92 cluster, miR-33, miR-146a, miR-150, miR-155, miR-181a, miR-222, miR-223, and miR-339. MiRNAs were first analyzed by miRNA microarray and thereafter validated by qRT-PCR. Sufficient RNA for qRT-PCR was available for 42 pediatric and 19 adult patients. RESULTS: Of the studied miRNAs, only miR-18a differed significantly in microarray analysis between adult and pediatric ALL, being lower in children (FC, -3.74; P, 0.0037). Results were confirmed by qRT-PCR (down-regulated in pediatric patients, P 0.003161). The other members of the miR-17-92 cluster did not differ significantly. CONCLUSIONS: Pediatric and adult patients with ALL have remarkably similar patterns of immune-cell-associated miRNAs in their bone marrow at diagnosis. However, the low expression of miR-18a in pediatric ALL is interesting and demands further study.
Subject(s)
Gene Expression , MicroRNAs/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Adult , Bone Marrow/pathology , Case-Control Studies , Child , Child, Preschool , Chromosome Aberrations , Computational Biology/methods , Female , Gene Expression Profiling , Gene Expression Regulation, Leukemic , Humans , Infant , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , RNA Interference , RNA, Messenger/genetics , Reproducibility of ResultsABSTRACT
PURPOSE: Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. METHODS: We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment. Plasma immunoglobulin levels were measured, and different B cell populations in PB and BM were analyzed with flow cytometry. RESULTS: Imatinib treatment decreased plasma IgA and IgG levels, while dasatinib reduced IgM levels. At diagnosis, the proportion of patients with IgA, IgG, and IgM levels below the lower limit of normal (LLN) was 0, 11, and 6% of all CML patients, respectively, whereas at 12 months timepoint the proportions were 6% (p = 0.13), 31% (p = 0.042) and 28% (p = 0.0078). Lower initial Ig levels predisposed to the development of hypogammaglobulinemia during TKI therapy. Decreased Ig levels in imatinib-treated patients were associated with higher percentages of immature BM B cells. The patients, who had low Ig levels during the TKI therapy, had significantly more frequent minor infections during the follow-up compared with the patients with normal Ig values (33% vs. 3%, p = 0.0016). No severe infections were reported, except recurrent upper respiratory tract infections in one imatinib-treated patient, who developed severe hypogammaglobulinemia. CONCLUSIONS: TKI treatment decreases plasma Ig levels, which should be measured in patients with recurrent infections.
Subject(s)
Immunity, Humoral/drug effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/administration & dosage , Adult , Aniline Compounds/administration & dosage , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Bone Marrow Cells/metabolism , Bone Marrow Cells/pathology , Dasatinib/administration & dosage , Female , Humans , Imatinib Mesylate/administration & dosage , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Nitriles/administration & dosage , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/administration & dosage , Quinolines/administration & dosage , Treatment OutcomeABSTRACT
Jagriti Innovations developed a collaboration tool in partnership with the Cure2Children Foundation that has been used by health professionals in Italy, Pakistan, and India for the collaborative management of patients undergoing bone marrow transplantation (BMT) for thalassemia major since August 2008. This online open-access database covers data recording, analyzing, and reporting besides enabling knowledge exchange, telemedicine, capacity building, and quality assurance. As of February 2014, over 2400 patients have been registered and 112 BMTs have been performed with outcomes comparable to international standards, but at a fraction of the cost. This approach avoids medical emigration and contributes to local healthcare strengthening and competitiveness. This paper presents the experience and clinical outcomes associated with the use of this platform built using open-source tools and focusing on a locally pertinent tertiary care procedure-BMT.
