13 research outputs found
Asymmetric Division and Lineage Commitment at the Level of Hematopoietic Stem Cells: Inference from Differentiation in Daughter Cell and Granddaughter Cell Pairs
How hematopoietic stem cells (HSCs) commit to a particular lineage is unclear. A high degree of HSC purification enabled us to address this issue at the clonal level. Single-cell transplantation studies revealed that 40% of the CD34â/low, c-Kit+, Sca-1+, and lineage markerâ (CD34âKSL) cells in adult mouse bone marrow were able, as individual cells, to reconstitute myeloid and B- and T-lymphoid lineages over the long-term. Single-cell culture showed that >40% of CD34âKSL cells could form neutrophil (n)/macrophage (m)/erythroblast (E)/megakaryocyte (M) (nmEM) colonies. Assuming that a substantial portion of long-term repopulating cells can be detected as nmEM cells within this population, we compared differentiation potentials between individual pairs of daughter and granddaughter cells derived in vitro from single nmEM cells. One of the two daughter or granddaughter cells remained an nmEM cell. The other showed a variety of combinations of differentiation potential. In particular, an nmEM cell directly gave rise, after one cell division, to progenitor cells committed to nm, EM, or M lineages. The probability of asymmetric division of nmEM cells depended on the cytokines used. These data strongly suggest that lineage commitment takes place asymmetrically at the level of HSCs under the influence of external factors
Dasatinib cessation after deep molecular response exceeding 2 years and natural killer cell transition during dasatinib consolidation
Tyrosine kinase inhibitors (TKI) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMR); some patients have successfully discontinued TKI therapy after maintaining DMR for â„1 year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for â„2 years. This study included 54 patients with CML who were enrolled in a DâSTOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2âyear consolidation. Peripheral lymphocyte profiles were analyzed by flow cytometry. The estimated 12âmonth treatmentâfree survival (TFS) was 62.9% (95% confidence interval: 48.5%â74.2%). During dasatinib consolidation, the percentage of total lymphocytes and numbers of CD3â» CD56âș natural killer (NK) cells, CD16âș CD56âș NK cells and CD56âș CD57âș NKâlarge granular lymphocytes (LGL) were significantly higher in patients with molecular relapse after discontinuation but remained unchanged in patients without molecular relapse for >7 months. At the end of consolidation, patients whose total lymphocytes comprised <41% CD3â» CD56âș NK cells, <35% CD16âș CD56âș NK cells, or <27% CD56âș CD57âș NKâLGL cells had higher TFS relative to other patients (77% vs 18%; P < .0008; 76% vs 10%; P < .0001; 84% vs 46%; P = .0059, respectively). The increase in the number of these NK cells occurred only during dasatinib consolidation. In patients with DMR, dasatinib discontinuation after 2âyear consolidation can lead to high TFS. This outcome depends significantly on a smaller increase in NK cells during dasatinib consolidation
Transcriptional Responses of a Bicarbonate-Tolerant Monocot, Puccinellia tenuiflora, and a Related Bicarbonate-Sensitive Species, Poa annua, to NaHCO3 Stress
Puccinellia tenuiflora is an alkaline salt-tolerant monocot found in saline-alkali soil in China. To identify the genes which are determining the higher tolerance of P. tenuiflora compared to bicarbonate sensitive species, we examined the responses of P. tenuiflora and a related bicarbonate-sensitive Poeae plant, Poa annua, to two days of 20 mM NaHCO3 stress by RNA-seq analysis. We obtained 28 and 38 million reads for P. tenuiflora and P. annua, respectively. For each species, the reads of both unstressed and stressed samples were combined for de novo assembly of contigs. We obtained 77,329 contigs for P. tenuiflora and 115,335 contigs for P. annua. NaHCO3 stress resulted in greater than two-fold absolute expression value changes in 157 of the P. tenuiflora contigs and 1090 of P. annua contigs. Homologs of the genes involved in Fe acquisition, which are important for the survival of plants under alkaline stress, were up-regulated in P. tenuiflora and down-regulated in P. annua. The smaller number of the genes differentially regulated in P. tenuiflora suggests that the genes regulating bicarbonate tolerance are constitutively expressed in P. tenuiflora
Adult paroxysmal cold hemoglobinuria following mRNA COVIDâ19 vaccination
Abstract Paroxysmal cold hemoglobinuria (PCH) is an extremely rare subtype of autoimmune hemolytic anemia (AIHA) in adults. PCH is caused by the biphasic DonathâLandsteiner (DL) antibody which fixes complement to red blood cells at low temperatures and dissociates at warmer temperatures, leading to complementâmediated intravascular hemolysis. Autoimmune hematological disorders including AIHA and immune thrombocytopenia have been reported to develop following the mRNA COVIDâ19 vaccination. However, PCH developing subsequent to mRNA vaccination has never been reported. We report a 59âyearâold male who developed PCH approximately a month after his second mRNA COVIDâ19 vaccination