Ultrasensitive quantitation of FLT3-ITD mutation in patients with acute myeloid leukemia using ddPCR.

Background: FLT3-ITD mutations occur in 45-50% of cytogenetically normal AML patients. Conventional fragment analysis using capillary electrophoresis is routinely used to quantitate FLT3-ITD mutations. Fragment analysis however has limited sensitivity.

Inhibition of Skp2 enhances doxorubicin-induced cell death in B cell precursor acute lymphoblastic leukemia.

S-phase kinase-associated protein 2 (Skp2) is a well-defined component of the Skp2-Culin1-F-box (SCF) E3 ubiquitin ligase complex, which is involved in cell cycle progression and considered a prognostic marker in cancers. Overexpression of Skp2 is frequently observed in patients with acute lymphoblastic leukemia (ALL). Inhibition of this protein may be a valuable strategy to induce apoptosis in malignant cells.

Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment.

Chromosomal translocations are the main etiological factor of hematologic malignancies. These translocations are generally the consequence of aberrant DNA double-strand break (DSB) repair. DSBs arise either exogenously or endogenously in cells and are repaired by major pathways, including non-homologous end-joining (NHEJ), homologous recombination (HR), and other minor pathways such as alternative end-joining (A-EJ).

MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies.

MYC oncogene is a transcription factor with a wide array of functions affecting cellular activities such as cell cycle, apoptosis, DNA damage response, and hematopoiesis. Due to the multi-functionality of MYC, its expression is regulated at multiple levels. Deregulation of this oncogene can give rise to a variety of cancers.

Plasma levels of norepinephrine and expression levels of ß2-adrenergic receptor gene correlate with the incidence of acute graft-versus-host disease.

Acute graft-versus-host disease is a major complication in allogeneic hematopoietic stem-cell transplantation. Epinephrine and norepinephrine are stress hormones which affect many cells, including immune cells through interaction with adrenergic receptors, mainly β2-adrenergic receptor. The immunomodulatory effects of epinephrine, norepinephrine, and signaling of the adrenergic receptor have been shown to decrease the probability of the acute graft-versus-host disease in animal models.

Utilization of CRISPR/Cas9 gene editing in cellular therapies for lymphoid malignancies.

The ability to change the genetic information of immune cells is a powerful tool for basic and clinical settings. CRISPR/Cas9 gene editing technology by providing an efficient approach has accelerated immune cell therapy of cancers. Lymphoid cancers comprise a wide array of disease including lymphoma, multiple myeloma and lymphocytic leukemia.

Immune checkpoints in hematologic malignancies: What made the immune cells and clinicians exhausted!

Hematologic malignancies comprise a considerable part of cancers with high mortality at any age. Since the introduction of hematopoietic stem cell transplantation (HSCT), the overall survival of patients dramatically increased. The main goal of HSCT is the induction of a graft-versus-leukemia effect to eradicate the residual cancer cells and also reconstitute a healthy immune system for patients.

Assessment of a poly-epitope candidate vaccine against Hepatitis B, C, and poliovirus in interaction with monocyte-derived dendritic cells: An ex-vivo study.

Design and application of epitope-based polyvalent vaccines have recently garnered attention as an efficient alternative for conventional vaccines. We previously have reported the in silico design of HHP antigen which encompasses the immune-dominant epitopes of Hepatitis B surface antigen (HBsAg), Hepatitis C core protein (HCVcp) and Poliovirus viral proteins (VPs). It has been shown that the HHP has desirable conformation to expose the epitopes, high antigenicity and other desired physicochemical and immunological properties.

Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate.

Hematopoietic stem cells (HSCs) are quiescent cells with self-renewal capacity and potential multilineage development. Various molecular regulatory mechanisms such as epigenetic modifications and transcription factor (TF) networks play crucial roles in establishing a balance between self-renewal and differentiation of HSCs. Histone/DNA methylations are important epigenetic modifications involved in transcriptional regulation of specific lineage HSCs via controlling chromatin structure and accessibility of DNA.

Effects of ABO incompatibility on the outcome of allogeneic hematopoietic stem cell transplantation.

Background: ABO compatibility between donor and recipient is no necessary in allogeneic hematopoietic stem cell transplantation (AHSCT). Incompatible transplantations can be divided into three groups based on the donor and recipient blood groups. The influence of each kind of incompatibilities on the outcome of patients does not seem to be consistent.

Evaluation of H3 histone methylation and colony formation in erythroid progenitors treated with thalidomide and sodium butyrate.

Objectives: β-thalassemia and sickle cell disease are hemoglobinopathies with reduced/absent β chains in the former and dysfunctional β chains in the latter. In both conditions, up-regulation of hemoglobin F through demethylation can alleviate the symptoms. This can be attained with drugs such as thalidomide and sodium butyrate.

Functional analysis of three recombinant A1-VWF domain mutants in comparison to wild type and plasma-derived VWF facilitates subtyping in type 2 von Willebrand disease.

Phenotypic diagnosis of VWD, in particular type 2, is challenging. Molecular diagnosis may fail to provide clarity since mutations within a short stretch of the same domain may cause various phenotypes, and since even experts will ascribe different subtypes to similar mutations. We assessed diagnostic difficulty in VWD by investigating five cases where phenotypic data was unclear.

Recombinant and plasma-derived factor VIII products induce distinct splenic cytokine microenvironments in hemophilia A mice.

The use of plasma-derived factor VIII (pdFVIII) concentrates in hemophilia A has been reported to result in reduced anti-FVIII antibody formation. In this study, we have investigated whether the cytokine microenvironment induced by pdFVIII has an influence on reducing anti-FVIII antibody titers in hemophilic mice. Microarray and confirmatory quantitative reverse transcription polymerase chain reaction (RT-PCR) experiments show that pdFVIII infusion causes a different transcriptional profile in dendritic cells than recombinant FVIII (rFVIII).

Molecular genetic testing of hemostasis and thrombosis in developing countries: achievements, hopes, and challenges.

In today's developing world, how do we define a "developing country"? What level of effort and resources is invested in diagnosis, patient care, and research in those countries that we define to be developing? In particular, what is the situation with respect to molecular genetic testing in these countries? How much has been achieved to date, and what are the challenges to further achievements? This article describes the current status, challenges, and future hopes with respect to molecular genetic testing in hemostasis and thrombosis from the perspective of experts from three countries: Brazil, Colombia, and Iran. These individuals have lived and practiced genetic testing in their countries and have also had the experience to work and/or interact with the developed world to enable an appreciation of the difference.

Anti-CD3 prevents factor VIII inhibitor development in hemophilia A mice by a regulatory CD4+CD25+-dependent mechanism and by shifting cytokine production to favor a Th1 response.

Non-Fc-receptor binding anti-CD3 Ab therapy, in the setting of several different autoimmune disorders, can induce antigen-specific and long-lasting immunologic tolerance. Because factor VIII (FVIII) inhibitor formation is the most serious treatment-related complication for hemophilia A patients, we tested the efficacy of anti-CD3 to prevent FVIII inhibitor formation in hemophilia A BALB/c and C57BL/6 mice. A short course of low-dose anti-CD3 significantly increased expression of CD25 and the proportion of CD4+CD25+ regulatory T cells in the spleen and potently prevented the production of inhibitory and non-neutralizing anti-FVIII antibodies in both strains of mouse.