Published in Experimental hematology
Although establishment and maintenance of mitochondria are essential for the production of massive amounts of heme in erythroblasts, mitochondria must be degraded upon terminal differentiation to red blood cells (RBCs), thus creating a biphasic regulatory process. Previously, we reported that iron deficiency in mice promotes mitochondrial retention...
Published in Experimental hematology
The bone marrow (BM) and spleen from patients with myelofibrosis (MF), as well as those from the Gata1low mouse model of the disease contain increased number of abnormal megakaryocytes. These cells express high levels of the adhesion receptor P-selectin on their surface, which triggers a pathologic neutrophil emperipolesis, leading to increased bio...
Published in Experimental hematology
The founder of all blood cells are hematopoietic stem cells (HSCs), which are rare stem cells that undergo key cell fate decisions to self-renew to generate more HSCs or to differentiate progressively into a hierarchy of different immature hematopoietic cell types to ultimately produce mature blood cells. These decisions are influenced both intrins...
Published in Experimental hematology
Next-generation sequencing technology, including whole-exome or whole-genome sequencing and target gene sequencing, has allowed the molecular characterization of somatic mutation spectrums in hematologic diseases. Mutations in Additional sex combs-like 1 (ASXL1), a chromatin regulator, are identified in clonal hematopoiesis of indeterminate potenti...
Published in Experimental hematology
The molecular mechanisms regulating key fate decisions of hematopoietic stem cells (HSCs) remain incompletely understood. Here, we targeted global shRNA libraries to primary human hematopoietic stem and progenitor cells (HSPCs) to screen for modifiers of self-renewal and differentiation, and identified metastasis-associated 1 (MTA1) as a negative r...
Published in Experimental hematology
Despite decades of research, standard therapies remain ineffective for most leukemias, pushing toward an essential unmet need for targeted drug screens. Moreover, preclinical drug testing is an important consideration for success of clinical trials without affecting non-transformed stem cells. Using the transgenic chronic myeloid leukemia (CML) mou...
Published in Experimental hematology
Metabolism impacts all cellular functions and plays a fundamental role in physiology. Metabolic regulation of hematopoiesis is dynamically regulated under steady-state and stress conditions. It is clear that hematopoietic stem cells (HSCs) impose different energy demands and flexibility during maintenance compared with stressed conditions. However,...
Published in Experimental hematology
Hematopoietic stem cells (HSCs) with age-associated somatic mutations that disproportionally contribute to hematopoiesis generate the condition known as clonal hematopoiesis (CH). While CH conveys increased risk of hematologic cancer, there is also strong association between CH and cardiovascular disease (CVD). Accumulating evidence suggests that i...
Published in Experimental hematology
Erythroid nuclear condensation is a complex process in which compaction to one-tenth its original size occurs in an active nucleus simultaneously undergoing transcription and cell division. We previously found that the nuclear exportin Exportin7 (Xpo7), which is erythroid- specific and highly induced during terminal erythropoiesis, facilitates nucl...
Published in Experimental hematology
5-Aza-2'-deoxycytidine (5-Aza-dC) is a demethylation agent known to deplete DNA methyltransferases (DNMTs) in leukemia cancer cells, and can restore the expression of their target genes in Jurkat cells. The goal of this study was to discern the potential effect of 5-Aza-dC on the invasion of T-ALL cells in acute lymphoblastic leukemia (ALL). The ro...
