Primary spinal ligament-derived cells (SLDCs) from cervical herniated nucleus pulposus tissue (control, Ctrl) and ossification of the posterior longitudinal ligament (OPLL) tissue of surgical patients were analyzed for pathogenesis elucidation. Here, we found that decreased levels of ferritin and increased levels of alkaline phosphatase (ALP), a bone formation marker, provoked osteogenesis in SLDCs in OPLL. SLDCs from the Ctrl and OPLL groups satisfied the definition of mesenchymal stem/stromal cells. RNA sequencing revealed that oxidative phosphorylation and the citric acid cycle pathway were upregulated in the OPLL group. SLDCs in the OPLL group showed increased mitochondrial mass, increased mitochondrial reactive oxygen species (ROS) production, decreased levels of ROS scavengers including ferritin. ROS and ferritin levels were upregulated and downregulated in a time-dependent manner, and both types of molecules repressed ALP. Osteogenesis was mitigated by apoferritin addition. We propose that enhancing ferritin levels might alleviate osteogenesis in OPLL.

This study aimed to determine the clinical impact of CD25+/CD123+ coexpression in adult B-cell acute lymphoblastic leukemia (B-ALL) cases. One hundred and twenty newly diagnosed B-ALL patients (≤60 years old) were included in this study. CD123 and CD25 expression on leukemic blast cells were assessed using flow cytometry. CD25+/CD123+ coexpression was detected in 40/120 B-ALL patients (33.3%). All B-ALL patients showed CD25+/CD123+ coexpression had lower induction of remission response and shorter overall survival as compared to B-ALL cases lacking coexpression. In conclusion, CD25+/CD123+ positive coexpression is a reliable flow cytometry marker for prediction of the outcome of adult B-ALL patients and could be used as a novel parameter for risk stratification of adult B-ALL cases.
Copyright © 2020 Salah Aref et al.

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder. It is characterized by the presence of the Philadelphia (Ph) chromosome, t(9;22)(q34.1;q11.2), which carries the BCR-ABL1 fusion gene. Tyrosine kinase inhibitors (TKIs) have markedly changed the treatment approach of CML and have become the first-line agents for almost all CML patients. However, certain patients experience resistance to these medications, which occurs through several mechanisms, including the accumulation of TKI-resistant chromosomal abnormalities. The present study reports a case of a 27-year-old Saudi male with CML receiving TKI treatment, who presented with precursor B-cell lymphoblastic crisis demonstrating the presence of the novel combined chromosomal abnormalities; non-Ph der(22), i(9) and der(20), carrying the BCR-ABL1 fusion gene. This case report adds to the literature on novel TKI-resistance-conferring chromosomal abnormalities and links them to precursor B-cell lymphoblastic crisis.

B lymphopoiesis declines with age, and in rabbits this occurs by 8 wk of age. We found that CFU fibroblasts (CFU-Fs) in the bone marrow (BM) decrease 10-fold by a few weeks of age and that the CFU-Fs preferentially differentiate into adipocytes instead of osteoblasts. BM becomes filled with fat spaces during this time, making rabbit a unique model to study the effects of accelerated fat accumulation on B lymphopoiesis. We show that adipocytes of both rabbit and human secrete a soluble factor(s) that inhibits B lymphopoiesis, and we tested if this inhibition was due to effects on the BM stroma or hematopoietic progenitors. Pretreatment of BM mononuclear cells with adipocyte conditioned medium dramatically inhibited their differentiation into proB cells in cocultures with OP9 stromal cells. In contrast, pretreatment of OP9 stromal cells with adipocyte conditioned medium had no effect on B lymphopoiesis. Using human hematopoietic stem cells, we show that inhibition by the adipocyte-derived factor occurred at the common lymphoid progenitor to preproB cell stage. We propose that the age-related decline in B lymphopoiesis is due to a decrease in CFU-Fs, an increase in adipocytes, and an adipocyte-derived factor that blocks B lymphopoiesis at the common lymphoid progenitor to preproB cell stage.

Pre-BCR signaling is a critical checkpoint in B cell development in which B-lineage cells expressing functional IgH μ-chain are selectively expanded. B cell development is delayed in mutant ali/ali rabbits because the a-allotype encoding V(H)1 gene, which is normally used in VDJ gene rearrangements in wt rabbits, is deleted, and instead, most B-lineage cells use the a-allotype encoding V(H)4 gene [V(H)4(a)], which results in a severe developmental block at the pre-B cell stage. We found that V(H)4(a)-utilizing pre-B cells exhibit reduced pre-BCR signaling and do not undergo normal expansion in vitro. Transduction of murine 38B9 pre-B cells with chimeric rabbit-VDJ mouse-Cμ encoding retroviruses showed V(H)4(a)-encoded μ-chains do not readily form signal-competent pre-BCR, thereby explaining the reduction in pre-BCR signaling and pre-B cell expansion. Development of V(H)4(a)-utilizing B cells can be rescued in vivo by the expression of an Igκ transgene, indicating that V(H)4(a)-μ chains are not defective for conventional BCR formation and signaling. The ali/ali rabbit model system is unique because V(H)4(a)-μ chains have the capacity to pair with a variety of conventional IgL chains and yet lack the capacity to form a signal-competent pre-BCR. This system could allow for identification of critical structural parameters that govern pre-BCR formation/signaling.