Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased bleeding tendency and thrombocytopenia. In fact, the precise pathogenesis of this disease is still not clear. Megakaryopoiesis involves complete differentiation of megakaryocyte (MK) progenitors to functional platelets. This complex process occurs in specific bone marrow (BM) niches composed of several hematopoietic and non-hematopoietic cell types, soluble factors, and extracellular matrix proteins. These specialized microenvironments sustain MK maturation and localization to sinusoids as well as platelet release into circulation. However, MKs in ITP patients show impaired maturation and signs of degradation. Intrinsic defects in MKs and their extrinsic environment have been implicated in altered megakaryopoiesis in this disease. In particular, aberrant expression of miRNAs directing MK proliferation, differentiation, and platelet production; defective MK apoptosis; and reduced proliferation and differentiation rate of the MSC compartment observed in these patients may account for BM defects in ITP. Furthermore, insufficient production of thrombopoietin is another likely reason for ITP development. Therefore, identifying the signaling pathways and transcription factors influencing the interaction between MKs and BM niche in ITP patients will contribute to increased platelet production in order to prevent incomplete MK maturation and destruction as well as BM fibrosis and apoptosis in ITP. In this review, we will examine the interaction and role of BM niches in orchestrating megakaryopoiesis in ITP patients and discuss how these factors can be exploited to improve the quality of patient treatment and prognosis.

Objective and Background: Chronic myeloid leukemia (CML) is a neoplastic disease whose genetic and cytogenetic changes play important roles in prognosis and treatment strategies. Philadelphia (Ph) translocation t(9;22)(q34;q11) is a diagnostic and prognostic biomarker in CML.

This study evaluated the incidence of sensory neural hearing loss (SNHL) in beta-thalassemia major patients treated with deferoxamine in Mofid Children's Hospital. Based on the patients' file review, this descriptive and cross-sectional study was performed in all thalassemia patients older than 5 years old who were treated with regular blood transfusion and deferoxamine pump injection during the year 2006. The first visit with the otolaryngologist was performed in all patients to demarcate the presence of cerumen, otitis, and congenital abnormalities of ears. Then pure tone audiometery in frequency ranges of 250-8000 Hz was performed. Data statistical analysis was done by Mann-Whitney, chi square, and Fisher tests. There were 67 patients over 5 years old in our study. Five patients (7.4%), including 2 boys and 3 girls, in the age range of 7-24 years (mean:17.8 +/- 6.6 years) had SNHL. Their hearing loss was bilateral and in the frequency range of 2000-4000 Hz, with a mean of 3200 +/- 836.66 Hz. There were no significant differences between SNHL and non-SNHL patients in age, sex, serum ferritin level, age of the first transfusion, starting age of deferoxamine infusion, or duration and dosage of deferoxamine therapy. It seems that SNHL is not directly related to the serum ferritin level or deferoxamine dosage and other factors, including genetic or constitutional characteristics, may be also related. On the other hand, this complication may occur with doses lower than 50 mg/kg/day of deferoxamine, so no dosage can be considered safe for this drug. Despite the results of this study, hearing evaluation of beta-thalassemia major patients by audiometry is recommended because of the importance of this complication and the consequent disabilities.

Pax5 transcription factor, also known as B-cell specific activator protein (BSAP), plays a dual role in the hematopoietic system. Pax5 expression is essential in B-cell precursors for normal differentiation and maturation of B-cells. On the other hand, it inhibits the differentiation and progress toward other lineages. The expression of this factor is involved in several aspects of B-cell differentiation, including commitment, immunoglobulin gene rearrangement, BCR signal transduction and B-cell survival, so that the deletion or inactivating mutations of Pax5 cause cell arrest in Pro-B-cell stage. In recent years, point mutations, deletions and various rearrangements in Pax5 gene have been reported in several types of human cancers. However, no clear relationship has been found between these aberrations and disease prognosis. Specific expression of Pax5 in B-cells can raise it as a marker for the diagnosis and differentiation of B-cell leukemias and lymphomas as well as account for remission or relapse. Extensive studies on Pax5 along with other genes and immunomarkers are necessary for decisive results in this regard.

: Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which increased platelet destruction and thrombocytopenia are diagnostic features. In fact, the exact pathogenesis of this disease is still unknown, but genetic changes can be a potential factor in the development of ITP. In this study, the relationship between polymorphisms with platelet destruction has been studied, which leads to decreased platelet count. Relevant literature was identified by a PubMed search (2000-2016) of English language papers using the terms 'ITP', 'polymorphism,' and 'immune system'. The majority of genetic changes (polymorphisms) occur in immune system genes, including interferon (IFN)-γ gene. These changes lead to the dysfunction of immune system and production of pathogenic antibodies against platelet surface glycoproteins such as glycoprotein IIb/IIIa, which eventually result in the destruction of platelets and increasing disease severity. In addition, IFN-γ as well as factors and cytokines involved in megakaryopoiesis, including stem cell factor and interleukin-3 (IL-3), leads to the differentiation of megakaryocytes and platelet release. Considering the fact that IFN-γ is a factor of inflammation and thrombocytopenia, coexistence of this cytokine with thrombopoietin, stem cell factor, and IL-3 results in megakaryocytes differentiation and platelet production, which can be effective to reduce disease severity and increase the platelet counts.

The impaired biosynthesis of the β-globin chain in β-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major β-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects. Metabolic parameters including glycemic and iron indices, hepatic and renal functions tests, oxidative stress markers, and AGEs (carboxymethyl-lysine and pentosidine) levels were measured. All parameters were significantly increased in β-thalassemia compared to the control except for glutathione levels. Blood glucose, iron, serum ferritin, non-transferrin-bound iron (NTBI), MDA, soluble form of low-density lipoprotein receptor, glutathione peroxidase, total reactive oxygen species (ROS), and AGE levels were significantly higher in the β-thalassemia patients. Iron and ferritin showed a significant positive correlation with pentosidine (P < 0.01) but not with carboxymethyl-lysine. The NTBI was markedly increased in the β-thalassemia patients, and its levels correlated significantly with both carboxymethyl-lysine and pentosidine (P < 0.05). Our findings confirm the oxidative status generated by the iron overload in β-thalassemia major patients and highlight the enhanced formation of AGEs, which may play an important role in the pathogenesis of β-thalassemia major.

Background: The process of antigen presentation to immune cells is an undeniable contributor to the pathogenesis of autoimmune diseases. Different studies have indicated several factors that are related to autoimmunity. Human Leukocyte Antigens (HLAs) are among such factors, which have a key role in autoimmunity because of their involvement in antigen presentation process. Methods: Relevant English language literature was searched and retrieved from Google Scholar search engine and PubMed database (1996-2018). The following keywords were used: "Human leukocyte antigen", "Behcet’s syndrome", "Rheumatoid arthritis", "Systemic lupus erythematosus", "Type 1 diabetes", "Celiac Disease" and "Autoimmunity". Results: There is a strong association between HLA alleles and autoimmune diseases. For instance, HLA-B alleles and Behcet’s syndrome are strongly correlated, and systemic lupus erythematosus and Type 1 diabetes are related to HLA-DQA1 and HLA-DQB1, respectively. Conclusion: Association between numerous HLA alleles and autoimmune diseases may justify and rationalize their use as biomarkers as well as possible diagnostic laboratory parameters.

Background: Autoimmune thrombocytopenia in immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and heparin-induced thrombocytopenia (HIT) is associated with immunologic degradation of platelets and reduced platelet counts in patients, leading to bleeding risk in patients. Considering the role of human leukocyte antigens (HLA) in the development of immune response, in this review, we examine the relationship between HLA and pathogenesis of the above-mentioned diseases. Methods: Relevant English-language literature was searched and retrieved from Google Scholar search engine and PubMed database (1979 to 2018). The following keywords were used: “Immune Thrombocytopenic purpura,” “Thrombotic Thrombocytopenic Purpura,” Human Leukocyte Antigen,” and “Heparin-induced thrombocytopenia.” Results: In autoimmune thrombocytopenia, HLA molecule presents self-antigens or foreign antigens similar to self-antigens, provoking an immune response against platelets that results in the degradation of platelets in peripheral blood and possible bleeding in the patient. For example, HLA-DRB1 *11 presents the self-antigen and induces an immune response against ADAMTS13, which is associated with thrombocytopenia in TTP patients. Conclusions: HLA alleles can be used as prognostic biomarkers for immunologic disorders of platelet such as ITP, TTP, and HIT. Different DRB1 alleles enable the assessment of resistance to common ITP treatments as well as disease prognosis. Due to the genetic association between HLA-DR1 and HLA-DQ1 alleles and the role of HLA-DRB1 *11 in TTP, the HLA-DQB1 *02: 02 allele may also play a role in TTP pathogenesis.