ABSTRACT
Today the regulatory role of microRNAs [miRs] is well characterized in many diverse cellular processes. MiR-based regulation is categorized under epigenetic regulatory mechanisms. These small non-coding RNAs participate in producing and maturing erythrocytes, expressing hematopoietic factors and regulating expression of globin genes by post-transcriptional gene silencing. The changes in expression of miRs [miR-144/-320/-451/-503] in thalassemic/sickle cells compared with normal erythrocytes may cause clinical severity. According to the suppressive effects of certain miRs [miR-15a/-16-1/-23a/-26b/-27a/-451] on a number of transcription factors [myeloblastosis oncogene [MYB], B-cell lymphoma 11A [BCL11A], GATA1, Krüppel-like factor 3 [KLF3] and specificity protein 1 [Sp1]] during beta globin gene expression, It has been possible to increasing ? globin gene expression and fetal hemoglobin [HbF] production. Therefore, this strategy can be used as a novel therapy in infusing HbF and improving clinical complications of patients with hemoglobinopathies
ABSTRACT
Hematopoietic stem/progenitor cells [HSPCs] which give rise to different blood cell types are present within the bone marrow microenvironment, especially in flat bones such as skull, vertebrae, pelvis and chest. Interacting factors such as stromal derived factor-1/CXCR4, very late antigen-4/vascular cell adhesion molecule-1, Lymphocyte function-associated antigen-1/ intercellular adhesion molecule-1 retain the cells in the microenvironment. Any factor affecting these links may lead to migration and mobilization of HSPCs into peripheral blood. Several factors are involved in hematopoietic stem cells [HSC] mobilization such as granulocyte-colony stimulating factor, sphingosine-1-phosphate, hepatocyte growth factor, complement system, plasminogen system and matrix metalloproteinases. In bone marrow transplantation, HSC is transferred to the recipient from bone marrow of the donor, which can be performed in two ways. In the first method, Jamshidi needle is used for aspiration of bone marrow to extract hematopoietic cells usually from the hip. The second method uses mobilizer factors such as granulocyte-colony stimulating factor and granulocyte-macrophage colony-stimulating factor to mobilize the HSC into peripheral blood. Mobilized hematopoietic stem cells are suitable for the bone marrow transplantation in leukemias such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocyte leukemia, Hairy cell leukemia, etc
ABSTRACT
Acute lymphoblastic leukemia[ALL] is due to early stage arrest of lymphoblast development. The translocation of Philadelphia [Ph] chromosome occurs as a result of the BCR-ABL fusion gene, which constitutively produced activated tyrosine kinase. This gene fusion is an important indicator for prognosis in ALL and is associated with poor overall survival and remission duration. BCR-ABL could interfere in establishment of ALL. Therefore, in this study, we will try to investigate most pathological aspects involved in BCR-ABL fusion. Strategies for genetic alterations in B-ALL pathogenesis are discussed. Then, the main cytogenetic changes and genetic subtypes for ALL are highlighted. Moreover, intermediate reactions between cancer stem cells [CSC] related to ALL, its niche and microenvironment is discussed. The main objective in this review is to understand the principle prognosis in ALL to introduce new approaches and treatment alternatives
ABSTRACT
Background and Aims: iron deficiency anemia [IDA] and beta thalassemia minor [BTM] are the most common hypochromic microcytic anemias, and it is regarded important to differentiate between them. Several formulae can be taken into consideration based on red blood cell [RBC] parameters in order to distinguish between these two disorders. Hence, the present study intended to evaluate the sensitivity as well as specificity of some of these formulae
Materials and Methods: in this cross-sectional study, IDA was diagnosed in 200 patients based on hypochromic and microcytic RBC appearance, reduced mean cell volume, mean cell hemoglobin and ferritin as well as increased total iron binding capacity. Furthermore, BTM was diagnosed via hypochromic microcytic appearance of RBC and increased hemoglobin A2 level. Then, IDA and BTM diagnosis were confirmed using the formulae of King-Green, Mentzer index, England and Fraser, Shine and Lal, Srivastava and Sirdah. The sensitivity and specificity of these formulae were calculated as well
Results: the study findings demonstrated that based on the study criteria, out of 200 patients with hypochromic microcytic RBC appearance, 120 were afflicted with IDA and 80 suffered from BTM. The formulae-based diagnosis demonstrated that King- Green formula was the most reliable one
Conclusions: although King-Green formula had the highest sensitivity and specificity and was the most reliable formula, none of the formulae revealed 100% sensitivity and specificity. As a result, making definitive distinction between IDA and BTM is not possible using these formulae
ABSTRACT
Beta-thalassemia is the most common single gene disorder worldwide, in which hemoglobin beta-chain production is decreased. Today, the life expectancy of thalassemic patients is increased because of a variety of treatment methods; however treatment related complications have also increased. The most common side effect is osteoporosis, which usually occurs in early adulthood as a consequence of increased bone resorption. Increased bone resorption mainly results from factors such as delayed puberty, diabetes mellitus, hypothyroidism, ineffective hematopoiesis as well as hyperplasia of the bone marrow, parathyroid gland dysfunction, toxic effect of iron on osteoblasts, growth hormone [GH] and insulin-like growth factor-1 [IGF-1] deficiency. These factors disrupt the balance between osteoblasts and osteoclasts by interfering with various molecular mechanisms and result in decreased bone density. Given the high prevalence of osteopenia and osteoporosis in thalassemic patients and complexity of their development process, the goal of this review is to evaluate the molecular aspects involved in osteopenia and osteoporosis in thalassemic patients, which may be useful for therapeutic purposes