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Journal Prestige (SJR): 6.434
Citation Impact (citeScore): 7
Number of Followers: 323  
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ISSN (Print) 0006-4971 - ISSN (Online) 1528-0020
Published by American Society of Hematology Homepage  [2 journals]
  • T-PLL: harmonizing criteria for research
    • Authors: Risitano A. M.
      Pages: 1113 - 1114
      Keywords: Free Research Articles
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019002303
      Issue No: Vol. 134, No. 14 (2019)
  • Pembrolizumab: living up to expectations
    • Authors: Ansell S. M.
      Pages: 1114 - 1115
      Keywords: Free Research Articles
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019002417
      Issue No: Vol. 134, No. 14 (2019)
  • Myelomas sound of silencing
    • Authors: Boise L. H.
      Pages: 1116 - 1117
      Keywords: Free Research Articles
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019002742
      Issue No: Vol. 134, No. 14 (2019)
  • Tissue factor pathway inhibitor primes monocytes for antiphospholipid
           antibody-induced thrombosis
    • Authors: Müller-Calleja, N; Hollerbach, A, Ritter, S, Pedrosa, D. G, Strand, D, Graf, C, Reinhardt, C, Strand, S, Poncelet, P, Griffin, J. H, Lackner, K. J, Ruf, W.
      Pages: 1119 - 1131
      Abstract: Antiphospholipid antibodies (aPLs) with complex lipid and/or protein reactivities cause complement-dependent thrombosis and pregnancy complications. Although cross-reactivities with coagulation regulatory proteins contribute to the risk for developing thrombosis in patients with antiphospholipid syndrome, the majority of pathogenic aPLs retain reactivity with membrane lipid components and rapidly induce reactive oxygen species-dependent proinflammatory signaling and tissue factor (TF) procoagulant activation. Here, we show that lipid-reactive aPLs activate a common species-conserved TF signaling pathway. aPLs dissociate an inhibited TF coagulation initiation complex on the cell surface of monocytes, thereby liberating factor Xa for thrombin generation and protease activated receptor 1/2 heterodimer signaling. In addition to proteolytic signaling, aPLs promote complement- and protein disulfide isomerase-dependent TF-integrin β1 trafficking that translocates aPLs and NADPH oxidase to the endosome. Cell surface TF pathway inhibitor (TFPI) synthesized by monocytes is required for TF inhibition, and disabling TFPI prevents aPL signaling, indicating a paradoxical prothrombotic role for TFPI. Myeloid cell-specific TFPI inactivation has no effect on models of arterial or venous thrombus development, but remarkably prevents experimental aPL-induced thrombosis in mice. Thus, the physiological control of TF primes monocytes for rapid aPL pathogenic signaling and thrombosis amplification in an unexpected crosstalk between complement activation and coagulation signaling.
      Keywords: Plenary Papers, Thrombosis and Hemostasis
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019001530
      Issue No: Vol. 134, No. 14 (2019)
  • Consensus criteria for diagnosis, staging, and treatment response
           assessment of T-cell prolymphocytic leukemia
    • Authors: Staber, P. B; Herling, M, Bellido, M, Jacobsen, E. D, Davids, M. S, Kadia, T. M, Shustov, A, Tournilhac, O, Bachy, E, Zaja, F, Porkka, K, Hoermann, G, Simonitsch-Klupp, I, Haferlach, C, Kubicek, S, Mayerhoefer, M. E, Hopfinger, G, Jaeger, U, Dearden, C.
      Pages: 1132 - 1143
      Abstract: T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course. With the advent of novel treatment options that will potentially change the management of patients with T-PLL, it has become necessary to produce consensus guidelines for the design and conduct of clinical trials. The T-PLL International Study group (TPLL-ISG) set out to define standardized criteria for diagnosis, treatment indication, and evaluation of response. These criteria will facilitate comparison of results from clinical trials in T-PLL, and will thus support clinical decision making, as well as the approval of new therapeutics by healthcare authorities.
      Keywords: Special Reports, Free Research Articles, Lymphoid Neoplasia
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019000402
      Issue No: Vol. 134, No. 14 (2019)
  • Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up
           of KEYNOTE-087
    • Authors: Chen, R; Zinzani, P. L, Lee, H. J, Armand, P, Johnson, N. A, Brice, P, Radford, J, Ribrag, V, Molin, D, Vassilakopoulos, T. P, Tomita, A, von Tresckow, B, Shipp, M. A, Lin, J, Kim, E, Nahar, A, Balakumaran, A, Moskowitz, C. H.
      Pages: 1144 - 1153
      Abstract: Programmed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5 months (range, 0.0+ to 27.0+ [+, no progressive disease at last assessment]) in all patients, 22.1 months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL. This trial was registered at as #NCT02453594.
      Keywords: Lymphoid Neoplasia, Clinical Trials and Observations
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019000324
      Issue No: Vol. 134, No. 14 (2019)
  • The KDM4/JMJD2 histone demethylases are required for hematopoietic stem
           cell maintenance
    • Authors: Agger, K; Nishimura, K, Miyagi, S, Messling, J.-E, Rasmussen, K. D, Helin, K.
      Pages: 1154 - 1158
      Abstract: KDM4/JMJD2 are H3K9- and H3K36-specific demethylases, which are considered promising therapeutic targets for the treatment of acute myeloid leukemia (AML) harboring MLL translocations. Here, we investigate the long-term effects of depleting KDM4 activity on normal hematopoiesis to probe potential side effects of continuous inhibition of these enzymes. Utilizing conditional Kdm4a/Kdm4b/Kdm4c triple-knockout mice, we show that KDM4 activity is required for hematopoietic stem cell (HSC) maintenance in vivo. The knockout of the KDM4 demethylases leads to accumulation of H3K9me3 on transcription start sites and the corresponding downregulation of expression of several genes in HSCs. We show that 2 of these genes, Taf1b and Nom1, are essential for the maintenance of hematopoietic cells. Taken together, our results show that the KDM4 demethylases are required for the expression of genes essential for the long-term maintenance of normal hematopoiesis.
      Keywords: Hematopoiesis and Stem Cells, Myeloid Neoplasia, Brief Reports
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019000855
      Issue No: Vol. 134, No. 14 (2019)
  • LMO2 activation by deacetylation is indispensable for hematopoiesis and
           T-ALL leukemogenesis
    • Authors: Morishima, T; Krahl, A.-C, Nasri, M, Xu, Y, Aghaallaei, N, Findik, B, Klimiankou, M, Ritter, M, Hartmann, M. D, Gloeckner, C. J, Stefanczyk, S, Lindner, C, Oswald, B, Bernhard, R, Hähnel, K, Hermanutz-Klein, U, Ebinger, M, Handgretinger, R, Casadei, N, Welte, K, Andre, M, Müller, P, Bajoghli, B, Skokowa, J.
      Pages: 1159 - 1175
      Abstract: Hematopoietic transcription factor LIM domain only 2 (LMO2), a member of the TAL1 transcriptional complex, plays an essential role during early hematopoiesis and is frequently activated in T-cell acute lymphoblastic leukemia (T-ALL) patients. Here, we demonstrate that LMO2 is activated by deacetylation on lysine 74 and 78 via the nicotinamide phosphoribosyltransferase (NAMPT)/sirtuin 2 (SIRT2) pathway. LMO2 deacetylation enables LMO2 to interact with LIM domain binding 1 and activate the TAL1 complex. NAMPT/SIRT2-mediated activation of LMO2 by deacetylation appears to be important for hematopoietic differentiation of induced pluripotent stem cells and blood formation in zebrafish embryos. In T-ALL, deacetylated LMO2 induces expression of TAL1 complex target genes HHEX and NKX3.1 as well as LMO2 autoregulation. Consistent with this, inhibition of NAMPT or SIRT2 suppressed the in vitro growth and in vivo engraftment of T-ALL cells via diminished LMO2 deacetylation. This new molecular mechanism may provide new therapeutic possibilities in T-ALL and may contribute to the development of new methods for in vitro generation of blood cells.
      Keywords: Lymphoid Neoplasia
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019000095
      Issue No: Vol. 134, No. 14 (2019)
  • PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation and
           broad H3K27me3 domain formation
    • Authors: Ren, Z; Ahn, J. H, Liu, H, Tsai, Y.-H, Bhanu, N. V, Koss, B, Allison, D. F, Ma, A, Storey, A. J, Wang, P, Mackintosh, S. G, Edmondson, R. D, Groen, R. W. J, Martens, A. C, Garcia, B. A, Tackett, A. J, Jin, J, Cai, L, Zheng, D, Wang, G. G.
      Pages: 1176 - 1189
      Abstract: Dysregulation of polycomb repressive complex 2 (PRC2) promotes oncogenesis partly through its enzymatic function for inducing trimethylation of histone H3 lysine 27 (H3K27me3). However, it remains to be determined how PRC2 activity is regulated in normal and diseased settings. We here report a PRC2-associated cofactor, PHD finger protein 19 (PHF19; also known as polycomb-like 3), as a crucial mediator of tumorigenicity in multiple myeloma (MM). Overexpression and/or genomic amplification of PHF19 is found associated with malignant progression of MM and plasma cell leukemia, correlating to worse treatment outcomes. Using various MM models, we demonstrated a critical requirement of PHF19 for tumor growth in vitro and in vivo. Mechanistically, PHF19-mediated oncogenic effect relies on its PRC2-interacting and chromatin-binding functions. Chromatin immunoprecipitation followed by sequencing profiling showed a critical role for PHF19 in maintaining the H3K27me3 landscape. PHF19 depletion led to loss of broad H3K27me3 domains, possibly due to impaired H3K27me3 spreading from cytosine guanine dinucleotide islands, which is reminiscent to the reported effect of an "onco"-histone mutation, H3K27 to methionine (H3K27M). RNA-sequencing–based transcriptome profiling in MM lines also demonstrated a requirement of PHF19 for optimal silencing of PRC2 targets, which include cell cycle inhibitors and interferon-JAK-STAT signaling genes critically involved in tumor suppression. Correlation studies using patient sample data sets further support a clinical relevance of the PHF19-regulated pathways. Lastly, we show that MM cells are generally sensitive to PRC2 inhibitors. Collectively, this study demonstrates that PHF19 promotes MM tumorigenesis through enhancing H3K27me3 deposition and PRC2’s gene-regulatory functions, lending support for PRC2 blockade as a means for MM therapeutics.
      Keywords: Multiple Myeloma, Lymphoid Neoplasia
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019000578
      Issue No: Vol. 134, No. 14 (2019)
  • A method for noninvasive prenatal diagnosis of monogenic autosomal
           recessive disorders
    • Authors: Cutts, A; Vavoulis, D. V, Petrou, M, Smith, F, Clark, B, Henderson, S, Schuh, A.
      Pages: 1190 - 1193
      Keywords: Sickle Cell Disease, Red Cells, Iron, and Erythropoiesis
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019002099
      Issue No: Vol. 134, No. 14 (2019)
  • Lymphocytes in Sanfilippo syndrome display characteristic Alder-Reilly
    • Authors: Do, L; Pasalic, L.
      Pages: 1194 - 1194
      Keywords: Free Research Articles, BloodWork
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019002412
      Issue No: Vol. 134, No. 14 (2019)
  • Cordua S, Kjaer L, Skov V, Pallisgaard N, Hasselbalch HC, Ellervik C.
           Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a
           Danish general population. Blood. 2019;134(5):469-479.
    • Pages: 1195 - 1195
      Keywords: Free Research Articles
      PubDate: 2019-10-03T09:00:30-07:00
      DOI: 10.1182/blood.2019002756
      Issue No: Vol. 134, No. 14 (2019)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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