ERCC6L2 defines a novel entity within inherited acute myeloid leukemia
(Source: Blood)
Source: Blood - June 19, 2019 Category: Hematology Authors: Douglas, S. P. M., Siipola, P., Kovanen, P. E., Pyörälä, M., Kakko, S., Savolainen, E.-R., Salmenniemi, U., Orte, K., Kytölä, S., Pitkänen, E., Porkka, K., Kilpivaara, O., Wartiovaara-Kautto, U. Tags: Myeloid Neoplasia Letter to Blood Source Type: research
Familial predisposition to TP53/complex karyotype MDS and leukemia in DNA repair-deficient xeroderma pigmentosum
(Source: Blood)
Source: Blood - June 19, 2019 Category: Hematology Authors: Sarasin, A., Quentin, S., Droin, N., Sahbatou, M., Saada, V., Auger, N., Boursin, Y., Dessen, P., Raimbault, A., Asnafi, V., Schmutz, J.-L., Taïeb, A., Menck, C. F. M., Rosselli, F., La Rochelle, L. D., Robert, C., Sicre de Fontbrune, F., Sebert, Tags: Myeloid Neoplasia Letter to Blood Source Type: research
Stimulated release of intraluminal vesicles from Weibel-Palade bodies
Weibel-Palade bodies (WPBs) are secretory granules that contain von Willebrand factor and P-selectin, molecules that regulate hemostasis and inflammation, respectively. The presence of CD63/LAMP3 in the limiting membrane of WPBs has led to their classification as lysosome-related organelles. Many lysosome-related organelles contain intraluminal vesicles (ILVs) enriched in CD63 that are secreted into the extracellular environment during cell activation to mediate intercellular communication. To date, there are no reports that WPBs contain or release ILVs. By light microscopy and live-cell imaging, we show that CD63 is enric...
Source: Blood - June 19, 2019 Category: Hematology Authors: Streetley, J., Fonseca, A.-V., Turner, J., Kiskin, N. I., Knipe, L., Rosenthal, P. B., Carter, T. Tags: Platelets and Thrombopoiesis, Vascular Biology Source Type: research
Inhibition of platelet GPVI induces intratumor hemorrhage and increases efficacy of chemotherapy in mice
Maintenance of tumor vasculature integrity is indispensable for tumor growth and thus affects tumor progression. Previous studies have identified platelets as major regulators of tumor vascular integrity, as their depletion selectively rendered tumor vessels highly permeable and caused massive intratumoral hemorrhage. While these results established platelets as potential targets for antitumor therapy, their depletion is not a treatment option due to their essential role in hemostasis. Thus, a detailed understanding of how platelets safeguard vascular integrity in tumors is urgently demanded. Here, we show for the first ti...
Source: Blood - June 19, 2019 Category: Hematology Authors: Volz, J., Mammadova-Bach, E., Gil-Pulido, J., Nandigama, R., Remer, K., Sorokin, L., Zernecke, A., Abrams, S. I., Ergün, S., Henke, E., Nieswandt, B. Tags: Platelets and Thrombopoiesis Source Type: research
Prognostic impact of circulating tumor DNA status post-allogeneic hematopoietic stem cell transplantation in AML and MDS
This study was performed to assess the utility of tumor-derived fragmentary DNA, or circulating tumor DNA (ctDNA), for identifying high-risk patients for relapse of acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloSCT). We retrospectively collected tumor and available matched serum samples at diagnosis and 1 and 3 months post-alloSCT from 53 patients with AML/MDS. After identifying driver mutations in 51 patients using next-generation sequencing, we designed at least 1 personalized digital polymerase chain reaction assay per...
Source: Blood - June 19, 2019 Category: Hematology Authors: Nakamura, S., Yokoyama, K., Shimizu, E., Yusa, N., Kondoh, K., Ogawa, M., Takei, T., Kobayashi, A., Ito, M., Isobe, M., Konuma, T., Kato, S., Kasajima, R., Wada, Y., Nagamura-Inoue, T., Yamaguchi, R., Takahashi, S., Imoto, S., Miyano, S., Tojo, A. Tags: Transplantation, Myeloid Neoplasia, Clinical Trials and Observations Source Type: research
Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants
Calreticulin (CALR) +1 frameshift mutations in exon 9 are prevalent in myeloproliferative neoplasms. Mutant CALRs possess a new C-terminal sequence rich in positively charged amino acids, leading to activation of the thrombopoietin receptor (TpoR/MPL). We show that the new sequence endows the mutant CALR with rogue chaperone activity, stabilizing a dimeric state and transporting TpoR and mutants thereof to the cell surface in states that would not pass quality control; this function is absolutely required for oncogenic transformation. Mutant CALRs determine traffic via the secretory pathway of partially immature TpoR, as t...
Source: Blood - June 19, 2019 Category: Hematology Authors: Pecquet, C., Chachoua, I., Roy, A., Balligand, T., Vertenoeil, G., Leroy, E., Albu, R.-I., Defour, J.-P., Nivarthi, H., Hug, E., Xu, E., Ould-Amer, Y., Mouton, C., Colau, D., Vertommen, D., Shwe, M. M., Marty, C., Plo, I., Vainchenker, W., Kralovics, R., Tags: Myeloid Neoplasia, Platelets and Thrombopoiesis Source Type: research
Role of urine immunofixation in the complete response assessment of MM patients other than light-chain-only disease
Response criteria for multiple myeloma (MM) require monoclonal protein (M-protein)–negative status on both serum immunofixation electrophoresis (sIFE) and urine (uIFE) immunofixation electrophoresis for classification of complete response (CR). However, uIFE is not always performed for sIFE-negative patients. We analyzed M-protein evaluations from 384 MM patients (excluding those with light-chain-only disease) treated in the GEM2012MENOS65 (NCT01916252) trial to determine the uIFE-positive rate in patients who became sIFE-negative posttreatment and evaluate rates of minimal residual disease (MRD)–negative statu...
Source: Blood - June 19, 2019 Category: Hematology Authors: Lahuerta, J.-J., Jimenez-Ubieto, A., Paiva, B., Martinez-Lopez, J., Gonzalez-Medina, J., Lopez-Anglada, L., Cedena, M.-T., Puig, N., Oriol, A., Blanchard, M.-J., Rios, R., Martin, J., Martinez, R., Sureda, A., Hernandez, M. T., de la Rubia, J., Krsnik, I. Tags: Multiple Myeloma, Free Research Articles, Myeloid Neoplasia, Lymphoid Neoplasia, CME article, Brief Reports, Clinical Trials and Observations Source Type: research
Activation of hedgehog signaling associates with early disease progression in chronic lymphocytic leukemia
Targeted sequencing of 103 leukemia-associated genes in leukemia cells from 841 treatment-naive patients with chronic lymphocytic leukemia (CLL) identified 89 (11%) patients as having CLL cells with mutations in genes encoding proteins that putatively are involved in hedgehog (Hh) signaling. Consistent with this finding, there was a significant association between the presence of these mutations and the expression of GLI1 (2 test, P < .0001), reflecting activation of the Hh pathway. However, we discovered that 38% of cases without identified mutations also were GLI1+. Patients with GLI1+ CLL cells had a shorter median t...
Source: Blood - June 19, 2019 Category: Hematology Authors: Ghia, E. M., Rassenti, L. Z., Neuberg, D. S., Blanco, A., Yousif, F., Smith, E. N., McPherson, J. D., Hudson, T. J., the HALT Pan-Leukemia Gene Panel Consortium, Harismendy, O., Frazer, K. A., Kipps, T. J. Tags: Lymphoid Neoplasia Source Type: research
Low vs high hemoglobin trigger for transfusion in vascular surgery: a randomized clinical feasibility trial
In conclusion, a perioperative protocol restricting RBC transfusion successfully separated hemoglobin levels and RBC units transfused. Exploratory outcomes suggested potential harm with the low-trigger group and warrant further trials before such a strategy is universally adopted. This trial was registered at www.clinicaltrials.gov as #NCT02465125. (Source: Blood)
Source: Blood - June 19, 2019 Category: Hematology Authors: Moller, A., Nielsen, H. B., Wetterslev, J., Pedersen, O. B., Hellemann, D., Winkel, P., Marcussen, K. V., Ramsing, B. G. U., Mortensen, A., Jakobsen, J. C., Shahidi, S. Tags: Transfusion Medicine, Clinical Trials and Observations Source Type: research
FouNdER mutations confer risk for leukemias
(Source: Blood)
Source: Blood - June 19, 2019 Category: Hematology Authors: Godley, L. A. Tags: Free Research Articles COMMENTS Source Type: research
WPBs and {alpha}-granules: more and more look-alike?
(Source: Blood)
Source: Blood - June 19, 2019 Category: Hematology Authors: Heijnen, H. F. G. Tags: Free Research Articles COMMENTS Source Type: research
GPVI inhibitor as antitumor gateway drug
(Source: Blood)
Source: Blood - June 19, 2019 Category: Hematology Authors: Goldfinger, L. E. Tags: Free Research Articles COMMENTS Source Type: research
Message from the void: MRD analysis from ctDNA
(Source: Blood)
Source: Blood - June 19, 2019 Category: Hematology Authors: Heuser, M., Lai, C. K. Tags: Free Research Articles COMMENTS Source Type: research
Mutated CALR: tails from the crypt
(Source: Blood)
Source: Blood - June 19, 2019 Category: Hematology Authors: Spivak, J. L. Tags: Free Research Articles COMMENTS Source Type: research
Hedgehog activation in CLL
(Source: Blood)
Source: Blood - June 19, 2019 Category: Hematology Authors: Chiodin, G., Forconi, F. Tags: Free Research Articles COMMENTS Source Type: research
