Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population
In conclusion, we present a novel population prevalence of CALR and a JAK2 V617F prevalence that is 3 to 30 times higher compared with less sensitive methods. Mutation-positive non-MPNs with elevated blood cell counts raise concerns of MPN underdiagnosis in the population. (Source: Blood)
Source: Blood - July 31, 2019 Category: Hematology Authors: Cordua, S., Kjaer, L., Skov, V., Pallisgaard, N., Hasselbalch, H. C., Ellervik, C. Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia Source Type: research
Frequency and prognostic impact of KIT and other genetic variants in indolent systemic mastocytosis
Indolent systemic mastocytosis (ISM) patients have a normal life expectancy, except in the 5% to 10% of cases that progress to more advanced SM (advSM), which has a significantly poorer outcome. Mutations in genes other than KIT frequently found in myeloid neoplasms have been associated with a poorer outcome among advSM, whereas limited information exists about their frequency and prognostic impact in ISM. We investigated the frequency and prognostic impact of variants in 18 genes, found to be altered in advSM, in 322 ISM patients (median follow-up, 5.7 years) divided into discovery (n = 200) and validation (n = 122) cohor...
Source: Blood - July 31, 2019 Category: Hematology Authors: Munoz-Gonzalez, J. I., Alvarez-Twose, I., Jara-Acevedo, M., Henriques, A., Vinas, E., Prieto, C., Sanchez-Munoz, L., Caldas, C., Mayado, A., Matito, A., Dasilva-Freire, N., Orfao, A., Garcia-Montero, A. C. Tags: Myeloid Neoplasia Source Type: research
Combined inhibition of Bcl-2 and NF{kappa}B synergistically induces cell death in cutaneous T-cell lymphoma
Therapeutic options for cutaneous T-cell lymphoma (CTCL) are limited and curative treatment regimens are not available. Thus, new targeted and well-tolerated therapeutic approaches are urgently needed. In this respect, we have recently shown that dimethyl fumerate (DMF) inhibits NF-B acting as a survival factor in CTCL. Similarly, inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) has been shown to induce cell death in CTCL especially when combined with histone deacetylase inhibitors. Therefore, we hypothesized that inhibition of Bcl-2 should potentiate NF-B inhibition in a novel combination treatment of CTC...
Source: Blood - July 31, 2019 Category: Hematology Authors: Froehlich, T. C., Müller-Decker, K., Braun, J. D., Albrecht, T., Schroeder, A., Gülow, K., Goerdt, S., Krammer, P. H., Nicolay, J. P. Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research
ROR1-targeted delivery of miR-29b induces cell cycle arrest and therapeutic benefit in vivo in a CLL mouse model
Chronic lymphocytic leukemia (CLL) occurs in 2 major forms: aggressive and indolent. Low miR-29b expression in aggressive CLL is associated with poor prognosis. Indiscriminate miR-29b overexpression in the B-lineage of mice causes aberrance, thus warranting the need for selective introduction of miR-29b into B-CLL cells for therapeutic benefit. The oncofetal antigen receptor tyrosine kinase orphan receptor 1 (ROR1) is expressed on malignant B-CLL cells, but not normal B cells, encouraging us with ROR1-targeted delivery for therapeutic miRs. Here, we describe targeted delivery of miR-29b to ROR1+ CLL cells leading to downre...
Source: Blood - July 31, 2019 Category: Hematology Authors: Chiang, C.-L., Goswami, S., Frissora, F. W., Xie, Z., Yan, P. S., Bundschuh, R., Walker, L. A., Huang, X., Mani, R., Mo, X. M., Baskar, S., Rader, C., Phelps, M. A., Marcucci, G., Byrd, J. C., Lee, L. J., Muthusamy, N. Tags: Lymphoid Neoplasia Source Type: research
Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma
Patients with relapsed or refractory multiple myeloma (RRMM) have limited treatment options and poor survival outcomes. The increasing adoption of lenalidomide-based therapy for frontline treatment of multiple myeloma has resulted in a need for effective regimens for lenalidomide-refractory patients. This phase 1b study evaluated daratumumab plus carfilzomib and dexamethasone (D-Kd) in patients with RRMM after 1 to 3 prior lines of therapy, including bortezomib and an immunomodulatory drug; lenalidomide-refractory patients were eligible. Carfilzomib- and daratumumab-naïve patients (n = 85) received carfilzomib week...
Source: Blood - July 31, 2019 Category: Hematology Authors: Chari, A., Martinez-Lopez, J., Mateos, M.-V., Blade, J., Benboubker, L., Oriol, A., Arnulf, B., Rodriguez-Otero, P., Pineiro, L., Jakubowiak, A., de Boer, C., Wang, J., Clemens, P. L., Ukropec, J., Schecter, J., Lonial, S., Moreau, P. Tags: Multiple Myeloma, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research
How targeted therapy disrupts the treatment paradigm for acquired TTP: the risks, benefits, and unknowns
Insights into immune-mediated thrombotic thrombocytopenic purpura (iTTP) pathophysiology have led to novel targeted therapies. Immunomodulatory strategies target anti-ADAMTS13 antibodies: rituximab is effective in inducing responses in refractory/relapsed TTP and increasing relapse-free survival; caplacizumab targets the von Willebrand factor–platelet interaction to hasten platelet count recovery and reduce mortality and TTP-related ischemic events. Bortezomib and recombinant ADAMTS13 are under investigation. This review examines how targeted therapies are disrupting current treatment paradigms to improve outcomes of...
Source: Blood - July 31, 2019 Category: Hematology Authors: Mazepa, M. A., Masias, C., Chaturvedi, S. Tags: Thrombocytopenia, Platelets and Thrombopoiesis, Thrombosis and Hemostasis, Blood Spotlight, Clinical Trials and Observations Source Type: research
Epo receptor marks the spot
(Source: Blood)
Source: Blood - July 31, 2019 Category: Hematology Authors: Paulson, R. F. Tags: Free Research Articles COMMENTS Source Type: research
T-cell prolymphocytic leukemia presenting as ascites
(Source: Blood)
Source: Blood - July 24, 2019 Category: Hematology Authors: Hermans, S. J. F., Sandberg, Y. Tags: Free Research Articles, BloodWork, Lymphoid Neoplasia BLOOD WORK Source Type: research
Trends in survival of young adult patients with acute lymphoblastic leukemia in Sweden and the United States
(Source: Blood)
Source: Blood - July 24, 2019 Category: Hematology Authors: Björkholm, M., Edgren, G., Dickman, P. W. Tags: Lymphoid Neoplasia, Clinical Trials and Observations Letter to Blood Source Type: research
Deficiency of adenosine deaminase 2 triggers adenosine-mediated NETosis and TNF production in patients with DADA2
Reduction of adenosine deaminase 2 (ADA2) activity due to autosomal-recessive loss-of-function mutations in the ADA2 gene (previously known as CECR1) results in a systemic vasculitis known as deficiency of ADA2 (DADA2). Neutrophils and a subset of neutrophils known as low-density granulocytes (LDGs) have been implicated in the pathogenesis of vasculitis, at least in part, through the formation of neutrophil extracellular traps (NETs). The study objective was to determine whether neutrophils and NETs play a pathogenic role in DADA2. In vivo evidence demonstrated NETs and macrophages in affected gastrointestinal tissue from ...
Source: Blood - July 24, 2019 Category: Hematology Authors: Carmona-Rivera, C., Khaznadar, S. S., Shwin, K. W., Irizarry-Caro, J. A., ONeil, L. J., Liu, Y., Jacobson, K. A., Ombrello, A. K., Stone, D. L., Tsai, W. L., Kastner, D. L., Aksentijevich, I., Kaplan, M. J., Grayson, P. C. Tags: Immunobiology and Immunotherapy, Phagocytes, Granulocytes, and Myelopoiesis Source Type: research
Cysteine depletion targets leukemia stem cells through inhibition of electron transport complex II
We have previously demonstrated that oxidative phosphorylation is required for the survival of human leukemia stem cells (LSCs) from patients with acute myeloid leukemia (AML). More recently, we demonstrated that LSCs in patients with de novo AML rely on amino acid metabolism to drive oxidative phosphorylation. Notably, although overall levels of amino acids contribute to LSC energy metabolism, our current findings suggest that cysteine may be of particular importance for LSC survival. We demonstrate that exogenous cysteine is metabolized exclusively to glutathione. Upon cysteine depletion, glutathione synthesis is impaire...
Source: Blood - July 24, 2019 Category: Hematology Authors: Jones, C. L., Stevens, B. M., DAlessandro, A., Culp-Hill, R., Reisz, J. A., Pei, S., Gustafson, A., Khan, N., DeGregori, J., Pollyea, D. A., Jordan, C. T. Tags: Myeloid Neoplasia, Brief Reports Source Type: research
NPM1c alters FLT3-D835Y localization and signaling in acute myeloid leukemia
Activating mutations in FMS-like tyrosine kinase receptor-3 (FLT3) and Nucleophosmin-1 (NPM1) are most frequent alterations in acute myeloid leukemia (AML), and are often coincidental. The mutational status of NPM1 has strong prognostic relevance to patients with point mutations of the FLT3 tyrosine kinase domain (TKD), but the biological mechanism underlying this effect remains unclear. In the present study, we investigated the effect of the coincidence of NPM1c and FLT3-TKD. Although expression of FLT3-TKD is not sufficient to induce a disease in mice, coexpression with NPM1c rapidly leads to an aggressive myeloprolifera...
Source: Blood - July 24, 2019 Category: Hematology Authors: Rudorf, A., Müller, T. A., Klingeberg, C., Kreutmair, S., Poggio, T., Gorantla, S. P., Rückert, T., Schmitt-Graeff, A., Gengenbacher, A., Paschka, P., Baldus, C., Zeiser, R., Vassiliou, G. S., Bradley, A., Duyster, J., Illert, A. L. Tags: Myeloid Neoplasia, Brief Reports Source Type: research
Gait speed, grip strength, and clinical outcomes in older patients with hematologic malignancies
This study aimed to evaluate whether gait speed and grip strength predicted clinical outcomes among older adults with blood cancers. We prospectively recruited 448 patients aged 75 years and older presenting for initial consultation at the myelodysplastic syndrome/leukemia, myeloma, or lymphoma clinic of a large tertiary hospital, who agreed to assessment of gait and grip. A subset of 314 patients followed for ≥6 months at local institutions was evaluated for unplanned hospital or emergency department (ED) use. We used Cox proportional hazard models calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for s...
Source: Blood - July 24, 2019 Category: Hematology Authors: Liu, M. A., DuMontier, C., Murillo, A., Hshieh, T. T., Bean, J. F., Soiffer, R. J., Stone, R. M., Abel, G. A., Driver, J. A. Tags: Free Research Articles, Myeloid Neoplasia, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research
Targeting glycogen synthase kinase 3 for therapeutic benefit in lymphoma
Targeting the B-cell receptor and phosphatidylinositol 3-kinase/mTOR signaling pathways has shown meaningful, but incomplete, antitumor activity in lymphoma. Glycogen synthase kinase 3 (GSK3) α and β are 2 homologous and functionally overlapping serine/threonine kinases that phosphorylate multiple protein substrates in several key signaling pathways. To date, no agent targeting GSK3 has been approved for lymphoma therapy. We show that lymphoma cells abundantly express GSK3α and GSK3β compared with normal B and T lymphocytes at the messenger RNA and protein levels. Utilizing a new GSK3 inhibitor 9-ING-...
Source: Blood - July 24, 2019 Category: Hematology Authors: Wu, X., Stenson, M., Abeykoon, J., Nowakowski, K., Zhang, L., Lawson, J., Wellik, L., Li, Y., Krull, J., Wenzl, K., Novak, A. J., Ansell, S. M., Bishop, G. A., Billadeau, D. D., Peng, K. W., Giles, F., Schmitt, D. M., Witzig, T. E. Tags: Lymphoid Neoplasia Source Type: research
Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy
The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy a...
Source: Blood - July 24, 2019 Category: Hematology Authors: Zucca, E., Rondeau, S., Vanazzi, A., Ostenstad, B., Mey, U. J. M., Rauch, D., Wahlin, B. E., Hitz, F., Hernberg, M., Johansson, A.-S., de Nully Brown, P., Hagberg, H., Ferreri, A. J. M., Lohri, A., Novak, U., Zander, T., Bersvendsen, H., Bargetzi, M., Min Tags: Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research
