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Diffuse large B-cell lymphoma in the elderly
(Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Tags: Free Research Articles, CME article CONTINUING MEDICAL EDUCATION (CME) QUESTIONS Source Type: research

Nasrallah R, Fast EM, Solaimani P, et al. Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes. Blood. 2016;128(15):1928-1939.
(Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Tags: Free Research Articles ERRATUM Source Type: research

Leukemic presentation of diffuse large B-cell lymphoma: an unusual pattern associated with splenic involvement
(Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Crane, G. M., Perkins, A. S. Tags: Free Research Articles, BloodWork, Lymphoid Neoplasia BLOOD WORK Source Type: research

A genome-wide association study of LCH identifies a variant in SMAD6 associated with susceptibility
(Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Peckham-Gregory, E. C., Chakraborty, R., Scheurer, M. E., Belmont, J. W., Abhyankar, H., Sengal, A. G., Scull, B. P., Eckstein, O., Zinn, D. J., Mayer, L., Shih, A., Merad, M., Parsons, D. W., McClain, K. L., Lupo, P. J., Allen, C. E. Tags: Pediatric Hematology, Myeloid Neoplasia, Phagocytes, Granulocytes, and Myelopoiesis Letter to Blood Source Type: research

CLEC-2 contributes to hemostasis independently of classical hemITAM signaling in mice
In this report, we present a novel knockin mouse model that maintains the expression of a CLEC-2 receptor that cannot signal through its hemITAM (Y7A KI). Remarkably, this mouse phenocopies the blood-lymphatic mixing and lethality of CLEC-2 KO models, but not their hemostatic/thrombotic defect. However, treatment of Y7A KI mice with Fab' fragments of the function-blocking anti–CLEC-2 antibody, INU1, resulted in a thrombus formation defect in vivo and ex vivo, revealing a hemITAM signaling–independent role for CLEC-2 in hemostasis and thrombosis. (Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Haining, E. J., Cherpokova, D., Wolf, K., Becker, I. C., Beck, S., Eble, J. A., Stegner, D., Watson, S. P., Nieswandt, B. Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis, Vascular Biology, Brief Reports Source Type: research

Degree of anemia, indirect markers of hemolysis, and vascular complications of sickle cell disease in Africa
In conclusion, severe anemia at steady state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy. (Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Dubert, M., Elion, J., Tolo, A., Diallo, D. A., Diop, S., Diagne, I., Sanogo, I., Belinga, S., Guifo, O., Wamba, G., Ngo Sack, F., Boidy, K., Kamara, I., Traore, Y., Diakite, C. O., Gbonon, V., Faye, B. F., Seck, M., Deme Ly, I., Chelo, D., NGuetta, R., D Tags: Sickle Cell Disease, Red Cells, Iron, and Erythropoiesis Source Type: research

H3K27M/I mutations promote context-dependent transformation in acute myeloid leukemia with RUNX1 alterations
Neomorphic missense mutations affecting crucial lysine residues in histone H3 genes significantly contribute to a variety of solid cancers. Despite the high prevalence of H3K27M mutations in pediatric glioblastoma and their well-established impact on global histone H3 lysine 27 di- and trimethylation (H3K27me2/3), the relevance of these mutations has not been studied in acute myeloid leukemia (AML). Here, we report the first identification of H3K27M and H3K27I mutations in patients with AML. We find that these lesions are major determinants of reduced H3K27me2/3 in these patients and that they are associated with common ab...
Source: Blood - November 16, 2017 Category: Hematology Authors: Lehnertz, B., Zhang, Y. W., Boivin, I., Mayotte, N., Tomellini, E., Chagraoui, J., Lavallee, V.-P., Hebert, J., Sauvageau, G. Tags: Myeloid Neoplasia Source Type: research

Prognostic significance of baseline metabolic tumor volume in relapsed and refractory Hodgkin lymphoma
Identification of prognostic factors for patients with relapsed/refractory Hodgkin lymphoma (HL) is essential for optimizing therapy with risk-adapted approaches. In our phase 2 study of positron emission tomography (PET)–adapted salvage therapy with brentuximab vedotin (BV) and augmented ifosfamide, carboplatin, and etoposide (augICE), we assessed clinical factors, quantitative PET assessments, and cytokine and chemokine values. Transplant-eligible patients with relapsed/refractory HL received 2 (cohort 1) or 3 (cohort 2) cycles of weekly BV; PET-negative patients (Deauville score ≤2) proceeded to autologous stem...
Source: Blood - November 16, 2017 Category: Hematology Authors: Moskowitz, A. J., Schöder, H., Gavane, S., Thoren, K. L., Fleisher, M., Yahalom, J., McCall, S. J., Cadzin, B. R., Fox, S. Y., Gerecitano, J., Grewal, R., Hamlin, P. A., Horwitz, S. M., Kumar, A., Matasar, M., Ni, A., Noy, A., Palomba, M. L., Pera Tags: Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

Rituximab-based first-line treatment of cGVHD after allogeneic SCT: results of a phase 2 study
This study was registered at www.clinicaltrials.gov as identifier NCT01135641. (Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Malard, F., Labopin, M., Yakoub-Agha, I., Chantepie, S., Guillaume, T., Blaise, D., Tabrizi, R., Magro, L., Vanhove, B., Blancho, G., Moreau, P., Gaugler, B., Chevallier, P., Mohty, M. Tags: Transplantation, Free Research Articles, Clinical Trials and Observations Source Type: research

Role of anthracycline and comprehensive geriatric assessment for elderly patients with diffuse large B-cell lymphoma
Survival outcome for elderly patients with newly diagnosed diffuse large B-cell lymphoma remains suboptimal in the rituximab era. In this systematic review, we summarize available evidence relevant to the inclusion of anthracycline in upfront chemoimmunotherapy for these elderly patients and highlight the need of prospective clinical trials. With limited prospective data, we find that pretreatment comprehensive geriatric assessment accurately predicts survival and treatment-related toxicities, suggesting its potential role in guiding overall treatment decision-making. (Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Lin, R. J., Behera, M., Diefenbach, C. S., Flowers, C. R. Tags: Free Research Articles, Lymphoid Neoplasia, CME article, Evidence-Based Focused Reviews, Clinical Trials and Observations Source Type: research

Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis
Current understanding of how platelets localize coagulation to wound sites has come mainly from studies of a subpopulation of activated platelets. In this review, we summarize data from the last 4 decades that have described these platelets with a range of descriptive titles and attributes. We identify striking overlaps in the reported characteristics of these platelets, which imply a single subpopulation of versatile platelets and thus suggest that their commonality requires unification of their description. We therefore propose the term procoagulant platelet as the unifying terminology. We discuss the agonist requirement...
Source: Blood - November 16, 2017 Category: Hematology Authors: Agbani, E. O., Poole, A. W. Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis, Review Articles Source Type: research

Thyroid hormone regulates hematopoiesis via the TR-KLF9 axis
Congenital hypothyroidism (CH) is one of the most prevalent endocrine diseases, for which the underlying mechanisms remain unknown; it is often accompanied by anemia and immunodeficiency in patients. Here, we created a severe CH model together with anemia and T lymphopenia to mimic the clinical features of hypothyroid patients by ethylnitrosourea (ENU) mutagenesis in Bama miniature pigs. A novel recessive c.1226A>G transition of the dual oxidase 2 (DUOX2) gene was identified as the causative mutation. This mutation hindered the production of hydrogen peroxide (H2O2) and thus contributed to thyroid hormone (TH) synthesis...
Source: Blood - November 16, 2017 Category: Hematology Authors: Zhang, Y., Xue, Y., Cao, C., Huang, J., Hong, Q., Hai, T., Jia, Q., Wang, X., Qin, G., Yao, J., Wang, X., Zheng, Q., Zhang, R., Li, Y., Luo, A., Zhang, N., Shi, G., Wang, Y., Ying, H., Liu, Z., Wang, H., Meng, A., Zhou, Q., Wei, H., Liu, F., Zhao, J. Tags: Hematopoiesis and Stem Cells, Plenary Papers Source Type: research

Platelet CLEC-2: a molecule with 2 faces
(Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Xia, L. Tags: Free Research Articles COMMENTS Source Type: research

Subphenotypes of sickle cell disease in Africa
(Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Piel, F. B., Williams, T. N. Tags: Free Research Articles COMMENTS Source Type: research

Mutant RUNX1 and histone tales
(Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Godley, L. A. Tags: Free Research Articles COMMENTS Source Type: research

Relapsed/refractory HL: FDG-PET is the trump card
(Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Gallamini, A. Tags: Free Research Articles COMMENTS Source Type: research

Miss Piggy on the catwalk again
(Source: Blood)
Source: Blood - November 16, 2017 Category: Hematology Authors: Migliaccio, A. R. Tags: Free Research Articles COMMENTS Source Type: research

Classical Hodgkin lymphoma arising in a patient with chronic lymphocytic leukemia (Richter syndrome)
(Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Quesada, A. E., Konoplev, S. Tags: Free Research Articles, BloodWork, Lymphoid Neoplasia BLOOD WORK Source Type: research

Aleukemic mast cell leukemia associated with chronic myelomonocytic leukemia and chronic lymphocytic leukemia
(Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Hu, Z., Konoplev, S. Tags: Hematopoiesis and Stem Cells, Free Research Articles, BloodWork, Myeloid Neoplasia, Lymphoid Neoplasia BLOOD WORK Source Type: research

Protocol II vs protocol III given twice during reinduction therapy in children with medium-risk ALL
(Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Locatelli, F., Valsecchi, M. G., Möricke, A., Zimmermann, M., Gruhn, B., Biondi, A., Kulozik, A. E., Silvestri, D., Bodmer, N., Putti, M. C., Burdach, S., Micalizzi, C., Teigler-Schlegel, A., Ritter, J., Pession, A., Cario, G., Bielack, S., Basso, Tags: Pediatric Hematology, Lymphoid Neoplasia, Clinical Trials and Observations Letter to Blood Source Type: research

An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD
B-cell receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B-cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B-cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy because NOTCH has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from hematopoietic stem cell transplantation patients with and without cGVHD. Consistent with a molecular link between pathways, we fou...
Source: Blood - November 9, 2017 Category: Hematology Authors: Poe, J. C., Jia, W., Su, H., Anand, S., Rose, J. J., Tata, P. V., Suthers, A. N., Jones, C. D., Kuan, P. F., Vincent, B. G., Serody, J. S., Horwitz, M. E., Ho, V. T., Pavletic, S. Z., Hakim, F. T., Owzar, K., Zhang, D., Blazar, B. R., Siebel, C. W., Chao, Tags: Immunobiology and Immunotherapy, Transplantation Source Type: research

Nonclassical FCGR2C haplotype is associated with protection from red blood cell alloimmunization in sickle cell disease
In conclusion, SCD patients with the FCGR2C.nc-ORF polymorphism have over a 3-fold lower risk for RBC alloimmunization in comparison with patients without this mutation. This protective effect was strongest for exposure to antigens other than the immunogenic Rh or K antigens. (Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Meinderts, S. M., Sins, J. W. R., Fijnvandraat, K., Nagelkerke, S. Q., Geissler, J., Tanck, M. W., Bruggeman, C., Biemond, B. J., Rijneveld, A. W., Kerkhoffs, J.-L. H., Pakdaman, S., Habibi, A., van Bruggen, R., Kuijpers, T. W., Pirenne, F., van den Berg, Tags: Sickle Cell Disease, Transfusion Medicine, Red Cells, Iron, and Erythropoiesis Source Type: research

The immunophilin FKBP12 inhibits hepcidin expression by binding the BMP type I receptor ALK2 in hepatocytes
The expression of the key regulator of iron homeostasis hepcidin is activated by the BMP-SMAD pathway in response to iron and inflammation and among drugs, by rapamycin, which inhibits mTOR in complex with the immunophilin FKBP12. FKBP12 interacts with BMP type I receptors to avoid uncontrolled signaling. By pharmacologic and genetic studies, we identify FKBP12 as a novel hepcidin regulator. Sequestration of FKBP12 by rapamycin or tacrolimus activates hepcidin both in vitro and in murine hepatocytes. Acute tacrolimus treatment transiently increases hepcidin in wild-type mice. FKBP12 preferentially targets the BMP receptor ...
Source: Blood - November 9, 2017 Category: Hematology Authors: Colucci, S., Pagani, A., Pettinato, M., Artuso, I., Nai, A., Camaschella, C., Silvestri, L. Tags: Red Cells, Iron, and Erythropoiesis Source Type: research

Selectin catch-bonds mechanotransduce integrin activation and neutrophil arrest on inflamed endothelium under shear flow
E-selectin extends from the plasma membrane of inflamed endothelium and serves to capture leukocytes from flowing blood via long-lived catch-bonds that support slow leukocyte rolling under shear stress. Its ligands are glycosylated with the tetrasaccharide sialyl Lewisx (sLex), which contributes to bond affinity and specificity. E-selectin-mediated rolling transmits signals into neutrophils that trigger activation of high-affinity β2-integrins necessary for transition to shear-resistant adhesion and transendothelial migration. Rivipansel is a glycomimetic drug that inhibits E-selectin-mediated vaso-occlusion induced b...
Source: Blood - November 9, 2017 Category: Hematology Authors: Morikis, V. A., Chase, S., Wun, T., Chaikof, E. L., Magnani, J. L., Simon, S. I. Tags: Immunobiology and Immunotherapy, Phagocytes, Granulocytes, and Myelopoiesis Source Type: research

CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation
CD177 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the antineutrophil cytoplasmic antibody antigen proteinase 3. CD177 associates with β2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM-1), suggesting a role in neutrophil migration. However, CD177pos neutrophils exhibit no clear migratory advantage in vivo, despite interruption of in vitro transendothelial migration by CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system, we found that CD177...
Source: Blood - November 9, 2017 Category: Hematology Authors: Bai, M., Grieshaber-Bouyer, R., Wang, J., Schmider, A. B., Wilson, Z. S., Zeng, L., Halyabar, O., Godin, M. D., Nguyen, H. N., Levescot, A., Cunin, P., Lefort, C. T., Soberman, R. J., Nigrovic, P. A. Tags: Immunobiology and Immunotherapy, Phagocytes, Granulocytes, and Myelopoiesis Source Type: research

Clonal chromosomal abnormalities appearing in Philadelphia chromosome-negative metaphases during CML treatment
Clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph–) metaphases emerge as patients with chronic phase chronic myeloid leukemia (CP-CML) are treated with tyrosine kinase inhibitors (TKIs). We assessed the characteristics and prognostic impact of 598 patients with CP-CML treated on clinical trials with various TKIs. CCA/Ph– occurred in 58 patients (10%); the most common were –Y in 25 (43%) and trisomy 8 in 7 patients (12%). Response to TKI therapy was similar for patients with CCA/Ph– and those without additional chromosomal abnormalities (ACAs). We further categorized CCA/Ph...
Source: Blood - November 9, 2017 Category: Hematology Authors: Issa, G. C., Kantarjian, H. M., Gonzalez, G. N., Borthakur, G., Tang, G., Wierda, W., Sasaki, K., Short, N. J., Ravandi, F., Kadia, T., Patel, K., Luthra, R., Ferrajoli, A., Garcia-Manero, G., Rios, M. B., Dellasala, S., Jabbour, E., Cortes, J. E. Tags: Myeloid Neoplasia, Clinical Trials and Observations Source Type: research

Synergy of BCL2 and histone deacetylase inhibition against leukemic cells from cutaneous T-cell lymphoma patients
The presence and degree of peripheral blood involvement in patients with cutaneous T-cell lymphoma (CTCL) portend a worse clinical outcome. Available systemic therapies for CTCL may variably decrease tumor burden and improve quality of life, but offer limited effects on survival; thus, novel approaches to the treatment of advanced stages of this non-Hodgkin lymphoma are clearly warranted. Mutational analyses of CTCL patient peripheral blood malignant cell samples suggested the antiapoptotic mediator B-cell lymphoma 2 (BCL2) as a potential therapeutic target. To test this, we developed a screening assay for evaluating the s...
Source: Blood - November 9, 2017 Category: Hematology Authors: Cyrenne, B. M., Lewis, J. M., Weed, J. G., Carlson, K. R., Mirza, F. N., Foss, F. M., Girardi, M. Tags: Lymphoid Neoplasia Source Type: research

Philadelphia chromosome-like acute lymphoblastic leukemia
Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as BCR-ABL1–like ALL, is a high-risk subset with a gene expression profile that shares significant overlap with that of Ph-positive (Ph+) ALL and is suggestive of activated kinase signaling. Although Ph+ ALL is defined by BCR-ABL1 fusion, Ph-like ALL cases contain a variety of genomic alterations that activate kinase and cytokine receptor signaling. These alterations can be grouped into major subclasses that include ABL-class fusions involving ABL1, ABL2, CSF1R, and PDGFRB that phenocopy BCR-ABL1 and alterations of CRLF2, JAK2, and...
Source: Blood - November 9, 2017 Category: Hematology Authors: Tasian, S. K., Loh, M. L., Hunger, S. P. Tags: Pediatric Hematology, Free Research Articles, Lymphoid Neoplasia, Review Articles, Clinical Trials and Observations Source Type: research

Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura
Safety, tolerability, and pharmacokinetics of recombinant ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; BAX 930; SHP655) were investigated in 15 patients diagnosed with severe congenital ADAMTS-13 deficiency (plasma ADAMTS-13 activity
Source: Blood - November 9, 2017 Category: Hematology Authors: Scully, M., Knöbl, P., Kentouche, K., Rice, L., Windyga, J., Schneppenheim, R., Hovinga, J. A. K., Kajiwara, M., Fujimura, Y., Maggiore, C., Doralt, J., Hibbard, C., Martell, L., Ewenstein, B. Tags: Plenary Papers, Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research

Notching up B-cell pathology in chronic GVHD
(Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Radojcic, V., Luznik, L. Tags: Free Research Articles COMMENTS Source Type: research

Fc{gamma}R and SCD alloimmunization: a nonclass(ical) act
(Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Yazdanbakhsh, K. Tags: Free Research Articles COMMENTS Source Type: research

Releasing the FKBP12 brake on hepcidin
(Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Parrow, N. L., Fleming, R. E. Tags: Free Research Articles COMMENTS Source Type: research

Tis one thing to adhere, another to migrate
(Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Kuckleburg, C. J. Tags: Free Research Articles COMMENTS Source Type: research

Prognostic relevance of CCAs/Ph- in CML settled
(Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Hehlmann, R. Tags: Free Research Articles COMMENTS Source Type: research

Recombinant ADAMTS-13: goodbye, allergic reactions!
(Source: Blood)
Source: Blood - November 9, 2017 Category: Hematology Authors: Sarode, R. Tags: Free Research Articles COMMENTS Source Type: research

Striking a chord
(Source: Blood)
Source: Blood - November 2, 2017 Category: Hematology Authors: Gardner, J.-A., Devitt, K. A. Tags: Free Research Articles, BloodWork BLOOD WORK Source Type: research

A dual role for the class III PI3K, Vps34, in platelet production and thrombus growth
This study uncovers a dual role for Vps34 as a regulator of platelet production by MKs and as an unexpected regulator of platelet activation and arterial thrombus formation dynamics. (Source: Blood)
Source: Blood - November 2, 2017 Category: Hematology Authors: Valet, C., Levade, M., Chicanne, G., Bilanges, B., Cabou, C., Viaud, J., Gratacap, M.-P., Gaits-Iacovoni, F., Vanhaesebroeck, B., Payrastre, B., Severin, S. Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research

Hematopoietic stem cell involvement in BCR-ABL1-positive ALL as a potential mechanism of resistance to blinatumomab therapy
We present 2 BCR-ABL1 fusion–positive BCP-ALL patients with CD19– myeloid lineage relapse after blinatumomab therapy and show BCR-ABL1 positivity in their hematopoietic stem cell (HSC)/progenitor/myeloid compartments at initial diagnosis by fluorescence in situ hybridization after cell sorting. By using the same approach with 25 additional diagnostic samples from patients with BCR-ABL1–positive BCP-ALL, we identified HSC involvement in 40% of the patients. Patients (6 of 8) with major BCR-ABL1 transcript encoding P210BCR-ABL1 mainly showed HSC involvement, whereas in most of the patients (9 of 12) with mi...
Source: Blood - November 2, 2017 Category: Hematology Authors: Nagel, I., Bartels, M., Duell, J., Oberg, H.-H., Ussat, S., Bruckmueller, H., Ottmann, O., Pfeifer, H., Trautmann, H., Gökbuget, N., Caliebe, A., Kabelitz, D., Kneba, M., Horst, H.-A., Hoelzer, D., Topp, M. S., Cascorbi, I., Siebert, R., Bru0 Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia, Brief Reports Source Type: research

Therapeutic potential of SGN-CD19B, a PBD-based anti-CD19 drug conjugate, for treatment of B-cell malignancies
Patients with relapsed/refractory B-cell malignancies such as non-Hodgkin lymphoma (B-NHL) or acute lymphoblastic leukemia have a poor prognosis. Despite measurable clinical activity with new targeted therapies, many patients do not achieve a complete or durable response suggesting an opportunity to improve upon existing therapies. Here we describe SGN-CD19B, a pyrrolobenzodiazepine (PBD)-based anti-CD19 antibody drug conjugate (ADC) being investigated for treatment of B-cell malignancies, which has improved potency compared with other ADCs. CD19-expressing tumor cells rapidly internalize SGN-CD19B, and the released PBD dr...
Source: Blood - November 2, 2017 Category: Hematology Authors: Ryan, M. C., Palanca-Wessels, M. C., Schimpf, B., Gordon, K. A., Kostner, H., Meyer, B., Yu, C., Van Epps, H. A., Benjamin, D. Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research

Ectopic ILT3 controls BCR-dependent activation of Akt in B-cell chronic lymphocytic leukemia
The high proportion of long-term nonprogressors among chronic lymphocytic leukemia (CLL) patients suggests the existence of a regulatory network that restrains the proliferation of tumor B cells. The identification of molecular determinants composing such network is hence fundamental for our understanding of CLL pathogenesis. Based on our previous finding establishing a deficiency in the signaling adaptor p66Shc in CLL cells, we undertook to identify unique phenotypic traits caused by this defect. Here we show that a lack of p66Shc shapes the transcriptional profile of CLL cells and leads to an upregulation of the surface ...
Source: Blood - November 2, 2017 Category: Hematology Authors: Zurli, V., Wimmer, G., Cattaneo, F., Candi, V., Cencini, E., Gozzetti, A., Raspadori, D., Campoccia, G., Sanseviero, F., Bocchia, M., Baldari, C. T., Kabanova, A. Tags: Lymphoid Neoplasia Source Type: research

Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice
In conclusion, we propose humanized mice as a robust model for human circadian studies and reveal insights on a novel molecular clock network in the human circadian rhythm. (Source: Blood)
Source: Blood - November 2, 2017 Category: Hematology Authors: Zhao, Y., Liu, M., Chan, X. Y., Tan, S. Y., Subramaniam, S., Fan, Y., Loh, E., Chang, K. T. E., Tan, T. C., Chen, Q. Tags: Immunobiology and Immunotherapy, Phagocytes, Granulocytes, and Myelopoiesis Source Type: research

Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS
Wilms’ tumor 1 (WT1) is constantly expressed in leukemic cells of acute leukemia and myelodysplastic syndrome (MDS). A T-cell receptor (TCR) that specifically reacts with WT1 peptide in the context of HLA-A*24:02 has been identified. We conducted a first-in-human trial of TCR–gene transduced T-cell (TCR–T-cell) transfer in patients with refractory acute myeloblastic leukemia (AML) and high-risk MDS to investigate the safety and cell kinetics of the T cells. The WT1-specific TCR-gene was transduced to T cells using a retroviral vector encoding small interfering RNAs for endogenous TCR genes. The T cells we...
Source: Blood - November 2, 2017 Category: Hematology Authors: Tawara, I., Kageyama, S., Miyahara, Y., Fujiwara, H., Nishida, T., Akatsuka, Y., Ikeda, H., Tanimoto, K., Terakura, S., Murata, M., Inaguma, Y., Masuya, M., Inoue, N., Kidokoro, T., Okamoto, S., Tomura, D., Chono, H., Nukaya, I., Mineno, J., Naoe, T., Emi Tags: Immunobiology and Immunotherapy, Myeloid Neoplasia, Clinical Trials and Observations, Gene Therapy Source Type: research

How I treat patients with HIV-related hematological malignancies using hematopoietic cell transplantation
Hematopoietic cell transplantation (HCT) has now been shown to be safe and effective for selected HIV-infected patients with hematological malignancies. Autologous HCT is now the standard of care for patients with HIV-related lymphomas who otherwise meet standard transplant criteria. Limited data also support use of allogeneic HCT (alloHCT) in selected HIV-infected patients who meet standard transplant criteria. We recommend enrolling patients in clinical trials that offer access to CCR532 homozygous donors, if available. HIV-infected patients requiring HCT may also be considered for participation in trials evaluating the ...
Source: Blood - November 2, 2017 Category: Hematology Authors: Alvarnas, J. C., Zaia, J. A., Forman, S. J. Tags: Immunobiology and Immunotherapy, Transplantation, How I Treat, Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

Emerging mechanisms of long noncoding RNA function during normal and malignant hematopoiesis
Long noncoding RNAs (lncRNAs) are increasingly recognized as vital components of gene programs controlling cell differentiation and function. Central to their functions is an ability to act as scaffolds or as decoys that recruit or sequester effector proteins from their DNA, RNA, or protein targets. lncRNA-modulated effectors include regulators of transcription, chromatin organization, RNA processing, and translation, such that lncRNAs can influence gene expression at multiple levels. Here we review the current understanding of how lncRNAs help coordinate gene expression to modulate cell fate in the hematopoietic system. W...
Source: Blood - November 2, 2017 Category: Hematology Authors: Alvarez-Dominguez, J. R., Lodish, H. F. Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia, Lymphoid Neoplasia, Review Articles Source Type: research

Anti-CD19 resistance can "stem" from progenitors
(Source: Blood)
Source: Blood - November 2, 2017 Category: Hematology Authors: Shah, N. N., Fry, T. J. Tags: Free Research Articles COMMENTS Source Type: research

Human and mouse leukocytes: different clockwork
(Source: Blood)
Source: Blood - November 2, 2017 Category: Hematology Authors: Mendez-Ferrer, S. Tags: Free Research Articles COMMENTS Source Type: research

Targeting WT1 in hematologic malignancies?
(Source: Blood)
Source: Blood - November 2, 2017 Category: Hematology Authors: Koehne, G. Tags: Free Research Articles COMMENTS Source Type: research

Atypical monoblasts with micronuclei
(Source: Blood)
Source: Blood - October 26, 2017 Category: Hematology Authors: Bouvier, S., Martin, M. Tags: Free Research Articles, BloodWork, Myeloid Neoplasia BLOOD WORK Source Type: research

Origins of myelodysplastic syndromes after aplastic anemia
(Source: Blood)
Source: Blood - October 26, 2017 Category: Hematology Authors: Negoro, E., Nagata, Y., Clemente, M. J., Hosono, N., Shen, W., Nazha, A., Yoshizato, T., Hirsch, C., Przychodzen, B., Mahfouz, R. Z., Kuzmanovic, T., Sekeres, M. A., Makishima, H., Ogawa, S., Maciejewski, J. P. Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia, Red Cells, Iron, and Erythropoiesis Letter to Blood Source Type: research

WIP deficiency severely affects human lymphocyte architecture during migration and synapse assembly
(Source: Blood)
Source: Blood - October 26, 2017 Category: Hematology Authors: Pfajfer, L., Seidel, M. G., Houmadi, R., Rey-Barroso, J., Hirschmugl, T., Salzer, E., Anton, I. M., Urban, C., Schwinger, W., Boztug, K., Dupre, L. Tags: Immunobiology and Immunotherapy Letter to Blood Source Type: research