Clinically indicated ibrutinib dose interruptions and reductions do not compromise long-term outcomes in CLL
(Source: Blood)
Source: Blood - May 29, 2019 Category: Hematology Authors: Ahn, I. E., Basumallik, N., Tian, X., Soto, S., Wiestner, A. Tags: Lymphoid Neoplasia, Clinical Trials and Observations Letter to Blood Source Type: research
Dysfunctional endogenous FIX impairs prophylaxis in a mouse hemophilia B model
Factor IX (FIX) binds to collagen IV (Col4) in the subendothelial basement membrane. In hemophilia B, this FIX-Col4 interaction reduces the plasma recovery of infused FIX and plays a role in hemostasis. Studies examining the recovery of infused BeneFix (FIXWT) in null (cross-reactive material negative, CRM–) hemophilia B mice suggest the concentration of Col4 readily available for binding FIX is ~405 nM with a 95% confidence interval of 374 to 436 nM. Thus, the vascular cache of FIX bound to Col4 is several-fold the FIX level measured in plasma. In a mouse model of prophylactic therapy (testing hemostasis by saphenou...
Source: Blood - May 29, 2019 Category: Hematology Authors: Cooley, B., Broze, G. J., Mann, D. M., Lin, F.-C., Pedersen, L. G., Stafford, D. W. Tags: Thrombosis and Hemostasis, Vascular Biology Source Type: research
Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia
Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying t...
Source: Blood - May 29, 2019 Category: Hematology Authors: Fields, M. E., Guilliams, K. P., Ragan, D., Binkley, M. M., Mirro, A., Fellah, S., Hulbert, M. L., Blinder, M., Eldeniz, C., Vo, K., Shimony, J. S., Chen, Y., McKinstry, R. C., An, H., Lee, J.-M., Ford, A. L. Tags: Sickle Cell Disease, Red Cells, Iron, and Erythropoiesis Source Type: research
Cleavage of anti-PF4/heparin IgG by a bacterial protease and potential benefit in heparin-induced thrombocytopenia
In conclusion, cleavage of anti-PF4/H IgG by IdeS abolishes heparin-dependent cellular activation induced by HIT antibodies. IdeS injection could be a potential treatment of patients with severe HIT. (Source: Blood)
Source: Blood - May 29, 2019 Category: Hematology Authors: Kizlik-Masson, C., Deveuve, Q., Zhou, Y., Vayne, C., Thibault, G., McKenzie, S. E., Pouplard, C., Loyau, S., Gruel, Y., Rollin, J. Tags: Thrombocytopenia, Platelets and Thrombopoiesis Source Type: research
Trib1 regulates eosinophil lineage commitment and identity by restraining the neutrophil program
Eosinophils and neutrophils are critical for host defense, yet gaps in understanding how granulocytes differentiate from hematopoietic stem cells (HSCs) into mature effectors remain. The pseudokinase tribbles homolog 1 (Trib1) is an important regulator of granulocytes; knockout mice lack eosinophils and have increased neutrophils. However, how Trib1 regulates cellular identity and function during eosinophilopoiesis is not understood. Trib1 expression markedly increases with eosinophil-lineage commitment in eosinophil progenitors (EoPs), downstream of the granulocyte/macrophage progenitor (GMP). Using hematopoietic- and eos...
Source: Blood - May 29, 2019 Category: Hematology Authors: Mack, E. A., Stein, S. J., Rome, K. S., Xu, L., Wertheim, G. B., Melo, R. C. N., Pear, W. S. Tags: Hematopoiesis and Stem Cells, Phagocytes, Granulocytes, and Myelopoiesis Source Type: research
PD-1/PD-L1 immune checkpoint and p53 loss facilitate tumor progression in activated B-cell diffuse large B-cell lymphomas
Refractory or relapsed diffuse large B-cell lymphoma (DLBCL) often associates with the activated B-cell-like (ABC) subtype and genetic alterations that drive constitutive NF-B activation and impair B-cell terminal differentiation. Here, we show that DNA damage response by p53 is a central mechanism suppressing the pathogenic cooperation of IKK2ca-enforced canonical NF-B and impaired differentiation resulting from Blimp1 loss in ABC-DLBCL lymphomagenesis. We provide evidences that the interplay between these genetic alterations and the tumor microenvironment select for additional molecular addictions that promote lymphoma p...
Source: Blood - May 29, 2019 Category: Hematology Authors: Pascual, M., Mena-Varas, M., Robles, E. F., Garcia-Barchino, M.-J., Panizo, C., Hervas-Stubbs, S., Alignani, D., Sagardoy, A., Martinez-Ferrandis, J. I., Bunting, K. L., Meier, S., Sagaert, X., Bagnara, D., Guruceaga, E., Blanco, O., Celay, J., Martinez-B Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research
Asrij/OCIAD1 suppresses CSN5-mediated p53 degradation and maintains mouse hematopoietic stem cell quiescence
Inactivation of the tumor suppressor p53 is essential for unrestrained growth of cancers. However, only 11% of hematological malignancies have mutant p53. Mechanisms that cause wild-type p53 dysfunction and promote leukemia are inadequately deciphered. The stem cell protein Asrij/OCIAD1 is misexpressed in several human hematological malignancies and implicated in the p53 pathway and DNA damage response. However, Asrij function in vertebrate hematopoiesis remains unknown. We generated the first asrij null (knockout [KO]) mice and show that they are viable and fertile with no gross abnormalities. However, by 6 months, they e...
Source: Blood - May 29, 2019 Category: Hematology Authors: Sinha, S., Dwivedi, T. R., Yengkhom, R., Bheemsetty, V. A., Abe, T., Kiyonari, H., VijayRaghavan, K., Inamdar, M. S. Tags: Hematopoiesis and Stem Cells Source Type: research
How I treat chronic myeloid leukemia in children and adolescents
Evidence-based recommendations have been established for treatment of chronic myeloid leukemia (CML) in adults treated with tyrosine kinase inhibitors (TKIs), but the rarity of this leukemia in children and adolescents makes it challenging to develop similar recommendations in pediatrics. In addition to imatinib, which was approved for pediatric CML in 2003, the second-generation TKIs dasatinib and nilotinib were recently approved for use in children, expanding the therapeutic options and pushing allogeneic stem cell transplantation to a third-line treatment of most pediatric cases. Yet, without sufficient data on efficacy...
Source: Blood - May 29, 2019 Category: Hematology Authors: Hijiya, N., Suttorp, M. Tags: Pediatric Hematology, How I Treat, Myeloid Neoplasia, Clinical Trials and Observations Source Type: research
RNA-binding proteins in hematopoiesis and hematological malignancy
RNA-binding proteins (RBPs) regulate fundamental processes, such as differentiation and self-renewal, by enabling the dynamic control of protein abundance or isoforms or through the regulation of noncoding RNA. RBPs are increasingly appreciated as being essential for normal hematopoiesis, and they are understood to play fundamental roles in hematological malignancies by acting as oncogenes or tumor suppressors. Alternative splicing has been shown to play roles in the development of specific hematopoietic lineages, and sequence-specific mutations in RBPs lead to dysregulated splicing in myeloid and lymphoid leukemias. RBPs ...
Source: Blood - May 29, 2019 Category: Hematology Authors: Hodson, D. J., Screen, M., Turner, M. Tags: Hematopoiesis and Stem Cells, Lymphoid Neoplasia, Review Articles Source Type: research
Tumor-educated platelets
Liquid biopsies have been considered the holy grail in achieving effective cancer management, with blood tests offering a minimally invasive, safe, and sensitive alternative or complementary approach for tissue biopsies. Currently, blood-based liquid biopsy measurements focus on the evaluation of biomarker types, including circulating tumor DNA, circulating tumor cells, extracellular vesicles (exosomes and oncosomes), and tumor-educated platelets (TEPs). Despite the potential of individual techniques, each has its own advantages and disadvantages. Here, we provide further insight into TEPs. (Source: Blood)
Source: Blood - May 29, 2019 Category: Hematology Authors: In 't Veld, S. G. J. G., Wurdinger, T. Tags: Platelets and Thrombopoiesis, Blood Spotlight Source Type: research
Brain O2 reserve in sickle cell disease
(Source: Blood)
Source: Blood - May 29, 2019 Category: Hematology Authors: Wood, J. C. Tags: Free Research Articles COMMENTS Source Type: research
New IDEaS for HIT treatment, anyone?
(Source: Blood)
Source: Blood - May 29, 2019 Category: Hematology Authors: Padmanabhan, A. Tags: Free Research Articles COMMENTS Source Type: research
Seronegative visceral leishmaniasis with bone marrow and hepatic involvement
(Source: Blood)
Source: Blood - May 22, 2019 Category: Hematology Authors: Martino, G., Ascani, S. Tags: Immunobiology and Immunotherapy, Free Research Articles, BloodWork, Phagocytes, Granulocytes, and Myelopoiesis BLOOD WORK Source Type: research
Reactive germinal centers in the bone marrow of an infant with autoimmune neutropenia
(Source: Blood)
Source: Blood - May 22, 2019 Category: Hematology Authors: Li, W., Iqbal, N. T. Tags: Hematopoiesis and Stem Cells, Pediatric Hematology, Immunobiology and Immunotherapy, Free Research Articles, BloodWork, Phagocytes, Granulocytes, and Myelopoiesis BLOOD WORK Source Type: research
Characteristics of patients with myeloproliferative neoplasms with lymphoma, with or without JAK inhibitor therapy
(Source: Blood)
Source: Blood - May 22, 2019 Category: Hematology Authors: Pemmaraju, N., Kantarjian, H., Nastoupil, L., Dupuis, M., Zhou, L., Pierce, S., Patel, K. P., Masarova, L., Cortes, J., Verstovsek, S. Tags: Myeloid Neoplasia, Lymphoid Neoplasia, Clinical Trials and Observations Letter to Blood Source Type: research
