Lack of Gdf11 does not improve anemia or prevent the activity of RAP-536 in a mouse model of {beta}-thalassemia
(Source: Blood)
Source: Blood - August 7, 2019 Category: Hematology Authors: Guerra, A., Oikonomidou, P. R., Sinha, S., Zhang, J., Lo Presti, V., Hamilton, C. R., Breda, L., Casu, C., La, P., Martins, A. C., Sendamarai, A. K., Fleming, M., Rivella, S. Tags: Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis Letter to Blood Source Type: research
Differential expression of Plg-RKT and its effects on migration of proinflammatory monocyte and macrophage subsets
Membrane-bound plasmin is used by immune cells to degrade extracellular matrices, which facilitates migration. The plasminogen receptor Plg-RKT is expressed by immune cells, including monocytes and macrophages. Among monocytes and macrophages, distinct subsets can be distinguished based on cell surface markers and pathophysiological function. We investigated expression of Plg-RKT by monocyte and macrophage subsets and whether potential differential expression might have functional consequences for cell migration. Proinflammatory CD14++CD16+ human monocytes and Ly6Chigh mouse monocytes expressed the highest levels of Plg-RK...
Source: Blood - August 7, 2019 Category: Hematology Authors: Thaler, B., Baik, N., Hohensinner, P. J., Baumgartner, J., Panzenböck, A., Stojkovic, S., Demyanets, S., Huk, I., Rega-Kaun, G., Kaun, C., Prager, M., Fischer, M. B., Huber, K., Speidl, W. S., Parmer, R. J., Miles, L. A., Wojta, J. Tags: Phagocytes, Granulocytes, and Myelopoiesis, Thrombosis and Hemostasis, Brief Reports Source Type: research
PRMT1-mediated FLT3 arginine methylation promotes maintenance of FLT3-ITD+ acute myeloid leukemia
The presence of FMS-like receptor tyrosine kinase-3 internal tandem duplication (FLT3-ITD) mutations in patients with acute myeloid leukemia (AML) is associated with poor clinical outcome. FLT3 tyrosine kinase inhibitors (TKIs), although effective in kinase ablation, do not eliminate primitive FLT3-ITD+ leukemia cells, which are potential sources of relapse. Thus, understanding the mechanisms underlying FLT3-ITD+ AML cell persistence is essential to devise future AML therapies. Here, we show that expression of protein arginine methyltransferase 1 (PRMT1), the primary type I arginine methyltransferase, is increased signific...
Source: Blood - August 7, 2019 Category: Hematology Authors: He, X., Zhu, Y., Lin, Y.-C., Li, M., Du, J., Dong, H., Sun, J., Zhu, L., Wang, H., Ding, Z., Zhang, L., Zhang, L., Zhao, D., Wang, Z., Wu, H., Zhang, H., Jiang, W., Xu, Y., Jin, J., Shen, Y., Perry, J., Zhao, X., Zhang, B., Liu, S., Xue, S.-L., Shen, B., Tags: Myeloid Neoplasia Source Type: research
IGF1R as druggable target mediating PI3K-{delta} inhibitor resistance in a murine model of chronic lymphocytic leukemia
Targeted therapy is revolutionizing the treatment of cancers, but resistance evolves against these therapies and derogates their success. The phosphatidylinositol 3-kinase delta (PI3K-) inhibitor idelalisib has been approved for treatment of chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma, but the mechanisms conferring resistance in a subset of patients are unknown. Here, we modeled resistance to PI3K- inhibitor in vivo using a serial tumor transfer and treatment scheme in mice. Whole-exome sequencing did not identify any recurrent mutation explaining resistance to PI3K- inhibitor. In the murine model, resistan...
Source: Blood - August 7, 2019 Category: Hematology Authors: Scheffold, A., Jebaraj, B. M. C., Tausch, E., Bloehdorn, J., Ghia, P., Yahiaoui, A., Dolnik, A., Blätte, T. J., Bullinger, L., Dheenadayalan, R. P., Li, L., Schneider, C., Chen, S.-S., Chiorazzi, N., Dietrich, S., Seiffert, M., Tannheimer, S., Do& Tags: Lymphoid Neoplasia Source Type: research
Oral idasanutlin in patients with polycythemia vera
A limited number of drugs are available to treat patients with polycythemia vera (PV) and essential thrombocythemia (ET). We attempted to identify alternative agents that may target abnormalities within malignant hematopoietic stem (HSCs) and progenitor cells (HPCs). Previously, MDM2 protein levels were shown to be upregulated in PV/ET CD34+ cells, and exposure to a nutlin, an MDM2 antagonist, induced activation of the TP53 pathway and selective depletion of PV HPCs/HSCs. This anticlonal activity was mediated by upregulation of p53 and potentiated by the addition of interferon-α2a (IFN-α2a). Therefore, we perfo...
Source: Blood - August 7, 2019 Category: Hematology Authors: Mascarenhas, J., Lu, M., Kosiorek, H., Virtgaym, E., Xia, L., Sandy, L., Mesa, R., Petersen, B., Farnoud, N., Najfeld, V., Rampal, R., Dueck, A., Hoffman, R. Tags: Myeloid Neoplasia, Clinical Trials and Observations Source Type: research
How I treat primary cutaneous CD30+ lymphoproliferative disorders
The primary cutaneous CD30+ lymphoproliferative disorders are a family of extranodal lymphoid neoplasms that arise from mature postthymic T cells and localize to the skin. Current classification systems recognize lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma, and borderline cases. In the majority of patients, the prognosis of primary cutaneous CD30+ lymphoproliferative disorders is excellent; however, relapses are common, and complete cures are rare. Skin-directed and systemic therapies are used as monotherapy or in combination to achieve the best disease control and minimize overall toxici...
Source: Blood - August 7, 2019 Category: Hematology Authors: Shinohara, M. M., Shustov, A. Tags: How I Treat, Lymphoid Neoplasia Source Type: research
Comprehensive viromewide antibody responses by systematic epitope scanning after hematopoietic cell transplantation
Further insight into humoral viral immunity after hematopoietic cell transplantation (HCT) could have potential impact on donor selection or monitoring of patients. Currently, estimation of humoral immune recovery is inferred from lymphocyte counts or immunoglobulin levels and does not address vulnerability to specific viral infections. We interrogated the viral antibody repertoire before and after HCT using a novel serosurvey (VirScan) that detects immunoglobulin G responses to 206 viruses. We performed VirScan on cryopreserved serum from pre-HCT and 30, 100, and 365 days after myeloablative HCT from 37 donor-recipient pa...
Source: Blood - August 7, 2019 Category: Hematology Authors: Bender Ignacio, R. A., Dasgupta, S., Stevens-Ayers, T., Kula, T., Hill, J. A., Lee, S. J., Mielcarek, M., Duerr, A., Elledge, S. J., Boeckh, M. Tags: Immunobiology and Immunotherapy, Plenary Papers Source Type: research
Factor IX for treating factor XI deficiency?
(Source: Blood)
Source: Blood - August 7, 2019 Category: Hematology Authors: Gailani, D. Tags: Free Research Articles COMMENTS Source Type: research
GDF11 is not the target of luspatercept
(Source: Blood)
Source: Blood - August 7, 2019 Category: Hematology Authors: Camaschella, C. Tags: Free Research Articles COMMENTS Source Type: research
FLT3-ITD gets by with a little help from PRMT1
(Source: Blood)
Source: Blood - August 7, 2019 Category: Hematology Authors: Gritsman, K. Tags: Free Research Articles COMMENTS Source Type: research
Resolving PI3K-{delta} inhibitor resistance in CLL
(Source: Blood)
Source: Blood - August 7, 2019 Category: Hematology Authors: Klein, U. Tags: Free Research Articles COMMENTS Source Type: research
Drug development challenges in polycythemia vera
(Source: Blood)
Source: Blood - August 7, 2019 Category: Hematology Authors: Ritchie, E. K. Tags: Free Research Articles COMMENTS Source Type: research
Viromewide antibody responses after transplantation
(Source: Blood)
Source: Blood - August 7, 2019 Category: Hematology Authors: Michonneau, D., Socie, G. Tags: Free Research Articles COMMENTS Source Type: research
Giant intracytoplasmic inclusions in a T-cell large granular lymphocytic leukemia patient with acute severe anemia
(Source: Blood)
Source: Blood - July 31, 2019 Category: Hematology Authors: Coffy, S., Shi, M. Tags: Free Research Articles, BloodWork, Lymphoid Neoplasia BLOOD WORK Source Type: research
Identification and transcriptome analysis of erythroblastic island macrophages
The erythroblastic island (EBI), composed of a central macrophage and surrounding erythroid cells, was the first hematopoietic niche discovered. The identity of EBI macrophages has thus far remained elusive. Given that Epo is essential for erythropoiesis and that Epor is expressed in numerous nonerythroid cells, we hypothesized that EBI macrophages express Epor so that Epo can act on both erythroid cells and EBI macrophages simultaneously to ensure efficient erythropoiesis. To test this notion, we used Epor-eGFPcre knockin mouse model. We show that in bone marrow (BM) and fetal liver, a subset of macrophages express Epor-e...
Source: Blood - July 31, 2019 Category: Hematology Authors: Li, W., Wang, Y., Zhao, H., Zhang, H., Xu, Y., Wang, S., Guo, X., Huang, Y., Zhang, S., Han, Y., Wu, X., Rice, C. M., Huang, G., Gallagher, P. G., Mendelson, A., Yazdanbakhsh, K., Liu, J., Chen, L., An, X. Tags: Red Cells, Iron, and Erythropoiesis Source Type: research
