Differential gene expression in umbilical cord blood and maternal peripheral blood.

Objectives: Umbilical cord blood (UCB) has become a useful alternative source of hematopoietic stem cells for clinical and research applications. UCB represents neonatal blood and differs from adult blood in many aspects, displaying different cell composition and various features of cellular immaturity. To understand molecular basis of phenotypic differences between neonatal and adult blood, we studied variations in transcriptome of UCB and maternal peripheral blood (PB).

MicroRNA expression profiles in umbilical cord blood cell lineages.

MicroRNAs (miRNAs), important regulators of cellular processes, show specific expression signatures in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation, indicating their role in the control of hematopoiesis. Because neonatal blood displays various features of immaturity, we might expect differential miRNA regulation. Herein, we determined miRNA expression profiles of umbilical cord blood (UCB) cell lineages and compared them to those of bone marrow (BM) and peripheral blood (PB) cell counterparts.

Erythropoiesis in polycythemia vera is hyper-proliferative and has accelerated maturation.

Polycythemia vera (PV) is an acquired myeloproliferative clonal disorder, characterized by augmented erythropoiesis. To better define PV pathogenesis, we performed an in vitro erythroid expansion from peripheral blood mononuclear cells of controls and PV patients and evaluated the cells for proliferation, apoptosis, erythroid differentiation, and morphology at the defined time points. PV erythroid progenitors exhibited increased proliferation at days 9-14 and accelerated maturation at days 7-14, with a larger S-phase population (40%) than controls (20%) at day 11; however, the proportion of apoptotic cells was comparable to controls.

High expression of ERCC1, FLT1, NME4 and PCNA associated with poor prognosis and advanced stages in myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) represents a good model for research of prognostic/progression markers due to frequent transformation into acute myeloid leukemia (AML). We analysed expression profiles of 26 MDS and 6 AML patients using cDNA arrays comprising 588 gene probes. The array data were validated in a larger set of 46 patients by qRT-PCR.

Differential expression of microRNAs in hematopoietic cell lineages.

Objectives: MicroRNAs (miRNAs) play key roles in a wide variety of normal and pathological cellular processes. A number of studies identified hematopoietic-specific miRNAs that are necessary for correct function of blood cells. Out of our microarray data, we chose 13 miRNAs that showed differential expression in peripheral blood cells (miR-15b, miR-16, miR-24, miR-30c, miR-106b, miR-142-3p, miR-142-5p, miR-150, miR-155, miR-181, miR-223, miR-342, and miR-451) and examined their expression in separated hematopoietic cell lineages.

Aberrant expression of microRNA in polycythemia vera.

Background: Polycythemia vera is a clonal hematopoietic stem cell disorder in which the JAK2 V617F mutation is observed in >95% of patients, but an as yet unidentified process appears to initiate the clonal expansion of hematopoiesis. Because microRNA regulate hematopoietic differentiation, we hypothesized that dysregulated expression of microRNA may contribute to the pathophysiology of polycythemia vera.

Design And Methods: We performed gene expression profiling in five patients with polycythemia vera and in five controls using CombiMatrix MicroRNA CustomArray.

Regulated expression of microRNAs in normal and polycythemia vera erythropoiesis.

Objective: Polycythemia vera (PV) is a myeloproliferative disorder, arising from the acquired mutation(s) of a hematopoietic stem cell. The JAK2 V617F somatic mutation is found in most PV patients; however, it is not the disease-initiating mutation. Because microRNAs (miRNAs) play a regulatory role in hematopoiesis, we studied miRNA expressions in PV and normal erythropoiesis.

Bmi-1 over-expression plays a secondary role in chronic myeloid leukemia transformation.

It has been demonstrated that over-expression of Bmi-1 occurs in a variety of cancers, including several types of leukemia. This gene plays a key role in the self-renewal of stem cells. Leukemic cells lacking Bmi-1 underwent proliferation arrest and showed signs of differentiation and apoptosis.

Targeting of gene expression by siRNA in CML primary cells.

Development of array methods contributes to elucidation of many genes expressed during oncogenesis. Our array-based analyses of gene expression in patients with chronic myeloid leukemia (CML) revealed several genes (MMP8, MMP9, PCNA, JNK2, MAPK p38) with significant increased expression. We suppose that the genes may be implicated in the disease development and a siRNA-suppression can elucidate their functions in leukemogenesis.

Expression analysis of PCNA gene in chronic myelogenous leukemia--combined application of siRNA silencing and expression arrays.

Imatinib metylase is the first choice treatment for BCR/ABL positive chronic myelogenous leukemia (CML). However, as some CML patients develop resistance to imatinib therapy, there is a significant interest in development of alternative treatment strategies, such as identifying targets other than BCR/ABL that may participate in CML. Previously, we demonstrated strong PCNA up-regulation in CML patients.

Array-based analysis of gene expression in childhood acute lymphoblastic leukemia.

Gene expression profiles of 10 children with acute lymphoblastic leukemia (ALL) were detected using cDNA arrays. Total RNAs were isolated from peripheral blood leukocytes of the patients at diagnosis. For detection of expression profiles we used Atlas Human Cancer cDNA Arrays (Clontech) with 588 genes.

Gene expression profiling in chronic myeloid leukemia patients treated with hydroxyurea.

Using array technology that allows the simultaneous detection of gene expression of hundreds of genes, four patients with chronic myeloid leukemia (CML) were investigated at diagnosis and after starting administration of hydroxyurea. To detect the gene expression of peripheral blood mononuclears and granulocytes Human Cancer cDNA Array (CLONTECH) with 588 gene probes was used. Gene expression mononuclear and granulocyte profiles of patients at diagnosis were compared with the control profiles.