Role of Genomic Biomarkers in Increasing Fetal Hemoglobin Levels Upon Hydroxyurea Therapy and in β-Thalassemia Intermedia: A Validation Cohort Study.

Hemoglobinopathies exhibit a remarkable phenotypic diversity in terms of disease severity, while individual genetic background plays a key role in differential response to drug treatment. In the last decade, genomic variants in genes located within, as well as outside the human β-globin cluster have been shown to be significantly associated with Hb F increase, in relation to hydroxyurea (HU) therapy in patients with these diseases. Here, we aim to determine the effect of genomic variants located in genes, such as , , , , , and , previously shown to modulate fetal hemoglobin (Hb F) levels in patients with β type hemoglobinopathies and reflecting disease severity and response to HU therapy in an independent cohort of Greek patients with these diseases.

First Report of a Coincidental Discovery of Hb Shimonoseki [α54(E3)Gln→Arg, HBA2: c.164A > G (or HBA1)] in a Greek Family.

The rare Hb Shimonoseki [α54(E3)Gln→Arg, HBA2: c.164A > G (or HBA1)] has been reported in Western Japan. Hb Shimonoseki seems to be an innocuous variant and few published data are available.

Impact of ZBTB7A hypomethylation and expression patterns on treatment response to hydroxyurea.

Background: We aimed to clarify the emerging epigenetic landscape in a group of genes classified as "modifier genes" of the β-type globin genes (HBB cluster), known to operate in trans to accomplish the two natural developmental switches in globin expression, from embryonic to fetal during the first trimester of conception and from fetal to adult around the time of birth. The epigenetic alterations were determined in adult sickle cell anemia (SCA) homozygotes and SCA/β-thalassemia compound heterozygotes of Greek origin, who are under hydroxyurea (HU) treatment. Patients were distinguished in HU responders and HU non-responders (those not benefited from the HU) and both, and in vivo and in vitro approaches were implemented.

National registry of hemoglobinopathies in Greece: updated demographics, current trends in affected births, and causes of mortality.

National registries constitute an invaluable source of information and contribute to the improvement of hemoglobinopathy management. Herein, we present the second updated report of the National Registry for Haemoglobinopathies in Greece (NRHG) and critically discuss the time trends in demographics, affected births, and causes of mortality. Thirty-eight Greek hemoglobinopathy units reported data from diagnosis to the last follow-up or death by retrospectively completing an electronic form.

Polyneuropathy and myopathy in beta-thalassemia major patients.

The thalassemias are the most common single gene disorder in the world. Nowadays, the average life expectancy of patients in developed countries has increased significantly, while, there was an increase of complications. We aimed to investigate peripheral neuropathy and myopathy in this patient group using a neurophysiological study.

Insulin Secretion and Resistance in Normoglycemic Patients with Sickle Cell Disease.

Diabetes mellitus has been described in chronic hemolytic anemias, but data are scarce regarding glucose metabolism in normoglycemic patients. To address this issue, we evaluated insulin sensitivity and secretion in patients with sickle cell disease (SCD) and normal oral glucose tolerance test (OGTT). Forty-five adult patients with homozygous sickle cell disease and Hb S/β-thalassemia (β-thal) (mean age 42.

Arterial Stiffness and Peripheral and Central Blood Pressure in Patients With Sickle Cell Disease.

Blood pressure (BP) in patients with sickle cell disease (SCD) has been reported to be lower than in persons in the general population. Data on arterial stiffness, which is an important risk factor for the progression of BP, are inconclusive for this patient population. Forty-five adult patients with SCD and 40 controls matched for sex, age, and body mass index were studied.

Response of biochemical markers of bone turnover to oral glucose load in diseases that affect bone metabolism.

Objective: Postprandial suppression of bone resorption is considered one of the main contributors in the circadian rhythm of bone turnover markers. The aim of this study was to investigate this physiological response of bone tissue in diseases that affect bone metabolism.

Patients And Methods: In this study, 118 patients (45 hypothyroid, 40 hyperthyroid, and 33 β-thalassemic patients) and 78 healthy individuals matched for age and body mass index were included.

Pregnancy in beta-thalassemia trait carriers: an uneventful journey.

Normochromic normocytic anemia during pregnancy reflects the significant increase in plasma volume, which disproportionately exceeds the increase in the red cell volume. In beta-thalassemia (beta-thal) trait carriers who become pregnant the plasma volume expansion may cause more pronounced anemia because the anemia of pregnancy is added to the pre-existed hypochromic microcytic anemia. In beta-thal women, pregnancy outcome and obstetric complications do not differ from the general population.

Non-Hodgkin's lymphomas in Greece according to the WHO classification of lymphoid neoplasms. A retrospective analysis of 810 cases.

The purpose of this retrospective study, the largest unselected series in our country, was to illustrate the clinicopathological features of non-Hodgkin's lymphoma (NHL) classified according to the World Health Organization (WHO) classification of lymphoid neoplasms. A retrospective analysis was conducted and clinical features of histological subtypes were established in 810 patients (age > or = 15 years) with NHL who were treated at 8 major centers representative of Greece. There were 435 males and 375 females 95% of them aged >30 years.

Amifostine stimulates the formation of hematopoietic bone marrow progenitors from B-cell chronic lymphocytic leukemia.

Amifostine is a phosphorylated aminothiol that not only protects hematopoietic progenitor cells from chemotherapy and radiotherapy, but also stimulates normal hematopoiesis. The effect of amifostine on the in vitro growth of hematopoietic progenitors derived from B-cell chronic lymphocytic leukemia(B-CLL) was investigated. The colony-forming units (CFU)-granulocyte macrophage (CFU-GM), the burst-forming units-erythroid (BFU-E) and the CFU-granulocyte erythroid macrophage megakaryocytes (CFU-GEMM) increased 38, 20 and 100%, respectively, after the incubation with amifostine.

Responsiveness to recombinant human erythropoietin (rh-Epo) of marrow erythroid progenitors (CFU-E and BFU-E) from B-chronic lymphocytic leukemia (B-CLL).

The responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to various concentrations of recombinant human erythropoietin (rh-Epo) (2,5,20,40,100,200 and 500 U/ml) was investigated in vitro in 18 patients with B-chronic lymphocytic leukemia to assess the clinical usefulness of rh-Epo in this disease. Bone marrow mononuclear cells were cultured by methylcellulose methods for CFU-E and BFU-E assays. The B-chronic lymphocytic leukemia patients were divided into two groups according to the percentage of lymphocytes in the bone marrow (under 70% and over 70%).

Increased peripheral blood normal myeloid progenitor cells (CFU-GM) in chronic lymphocytic leukemia: a perspective for autologous peripheral blood stem cell transplantation.

We assayed granulocyte-macrophage committed progenitor cells (CFU-GM) in the peripheral blood of 34 patients with chronic lymphocytic leukemia (CLL) and 12 normal individuals. The patients were divided into separate groups on the basis of previous therapy (i.e.