Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML project.
We report the technical cross-validation results for next-generation sequencing panel genes during the standardization process and the clinical validation in 823 samples of 751 patients with newly diagnosed or refractory/relapse acute myeloid leukemia. Two cross-validation rounds were performed in seven nationwide reference laboratories in order to reach a consensus regarding quality metrics criteria and variant reporting. In the pre-standardization cross-validation round, an overall concordance of 60.98% was obtained with a great variability in selected genes and conditions across laboratories. After consensus of relevant...
Source: Haematologica - November 12, 2020 Category: Hematology Authors: Sargas C, Ayala R, Chillón MC, Larráyoz MJ, Carrillo-Cruz E, Bilbao C, Yébenes-Ramírez M, Llop M, Rapado I, García-Sanz R, Vázquez I, Soria E, Florido-Ortega Y, Janusz K, Botella C, Serrano J, Martínez-Cuadrón D, Bergua J, Amigo ML, Martínez-Sán Tags: Haematologica Source Type: research

A prognostic index predicting survival in transformed Waldenstr öm macroglobulinemia.
The objective of this study was to develop and validate a prognostic index for survival in transformed WM patients. Through this multicenter, international collaborative effort, we developed a scoring system based on data from 133 patients with transformed WM who were evaluated between 1995 and 2016 (training cohort). Univariate and multivariate analyses were used to propose a prognostic index with 2-year survival after transformation as an end-point. For external validation, a data set of 67 patients was used to evaluate the performance of the model (validation cohort). By multivariate analysis, three adverse covariates w...
Source: Haematologica - November 12, 2020 Category: Hematology Authors: Durot E, Kanagaratnam L, Zanwar S, Kastritis E, D'Sa S, Garcia-Sanz R, Tomowiak C, Hivert B, Toussaint E, Protin C, Abeykoon JP, Guerrero-Garcia T, Itchaki G, Vos JM, Michallet AS, Godet S, Dupuis J, Leprêtre S, Bomsztyk J, Morel P, Leblond V, Treon SP, Tags: Haematologica Source Type: research

Structural aberrations are associated with poor survival in patients with clonal cytopenia of undetermined significance.
æk K Abstract Not available. PMID: 33179473 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 12, 2020 Category: Hematology Authors: Mikkelsen SU, Safavi S, Dimopoulos K, O'Rourke CJ, Andersen MK, Holm MS, Marcher CW, Andersen JB, Hansen JW, Grønbæk K Tags: Haematologica Source Type: research

Rapid decline in estimated glomerular filtration rate in sickle cell anemia: results of a multicenter pooled analysis.
Abstract Not available. PMID: 33179474 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 12, 2020 Category: Hematology Authors: Ataga KI, Zhou Q, Derebail VK, Saraf SL, Hankins JS, Loehr LR, Garrett ME, Ashley-Koch AE, Cai J, Telen MJ Tags: Haematologica Source Type: research

Homozygous Southeast Asian Ovalocytosis in five live-born neonates.
Abstract Not available. PMID: 33179475 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 12, 2020 Category: Hematology Authors: Lavinya AA, Razali RA, Razak MA, Mohamed R, Moses EJ, Soundararajan M, Bruce LJ, Eswaran J, Yusoff NM Tags: Haematologica Source Type: research

Inherited platelet diseases with normal platelet count: phenotypes, genotypes and diagnostic strategy.
Abstract Inherited platelet disorders resulting from platelet function defects and a normal platelet count cause a moderate or severe bleeding diathesis. Since the description of Glanzmann thrombasthenia resulting from defects of ITGA2B and ITGB3, new inherited platelet disorders have been discovered, facilitated by the use of high throughput sequencing and genomic analyses. Defects of RASGRP2 and FERMT3 responsible for severe bleeding syndromes and integrin activation have illustrated the critical role of signaling molecules. Important are mutations of P2RY12 encoding the major ADP receptor causal for an inherite...
Source: Haematologica - November 5, 2020 Category: Hematology Authors: Nurden P, Stritt S, Favier R, Nurden AT Tags: Haematologica Source Type: research

Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or naturalkiller/T-cell lymphoma.
Abstract Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose (MTD) of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory (R/R) T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with R/R TCL and NKTL were treated with standard dose ICE, dexamethasone 20mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose level (DL) 1, 2 and 3 were 40, 60 and 80mg respectively. Eleven p...
Source: Haematologica - November 5, 2020 Category: Hematology Authors: Tang T, Martin P, Somasundaram N, Lim C, Tao M, Poon E, Yunon MJ, Toh SQ, Yan SX, Farid M, Chan JY, Lim ST Tags: Haematologica Source Type: research

Expression of the chemokine receptor CCR1 promotes the dissemination of multiple myeloma plasma cells < em > in vivo < /em > .
Expression of the chemokine receptor CCR1 promotes the dissemination of multiple myeloma plasma cells in vivo. Haematologica. 2020 Nov 05;Online ahead of print:0 Authors: Zeissig MN, Hewett DR, Panagopoulos V, Mrozik KM, To LB, Croucher PI, Zannettino ACW, Vandyke K Abstract Multiple myeloma (MM) disease progression is dependent on the ability of MM plasma cells (PCs) to egress from the bone marrow (BM), enter the circulation and disseminate to distal BM sites. Expression of the chemokine CXCL12 by BM stromal cells is crucial for MM PC retention within the BM. However, the mechanisms which overcome CX...
Source: Haematologica - November 5, 2020 Category: Hematology Authors: Zeissig MN, Hewett DR, Panagopoulos V, Mrozik KM, To LB, Croucher PI, Zannettino ACW, Vandyke K Tags: Haematologica Source Type: research

PVRIG is a novel NK cell immune checkpoint receptor in acute myeloid leukemia.
This study explored the novel immune checkpoint poliovirus receptor-related immunoglobulin domain-containing (PVRIG) in acute myeloid leukemia (AML). We showed that AML patient blasts consistently expressed the PVRIG ligand (poliovirus receptor-related 2, PVRL2). Furthermore, PVRIG blockade significantly enhanced NK cell killing of PVRL2+, poliovirus receptor (PVR)lo AML cell lines, and significantly increased NK cell activation and degranulation in the context of patient primary AML blasts. However, in AML patient bone marrow, NK cell PVRIG expression levels were not increased. To understand how PVRIG blockade might poten...
Source: Haematologica - November 5, 2020 Category: Hematology Authors: Li J, Whelan S, Kotturi MF, Meyran D, D'Souza C, Hansen K, Liang S, Hunter J, Trapani JA, Neeson PJ Tags: Haematologica Source Type: research

Multiclonal complexity of pediatric acute lymphoblastic leukemia and the prognostic relevance of subclonal mutations.
Abstract Genomic studies of pediatric acute lymphoblastic leukemia (ALL) have shown remarkable heterogeneity in initial diagnosis, with multiple (sub)clones harboring lesions in relapse-associated genes. However, the clinical relevance of these subclonal alterations remains unclear. We assessed the clinical relevance and prognostic value of subclonal alterations in the relapse-associated genes IKZF1, CREBBP, KRAS, NRAS, PTPN11, TP53, NT5C2, and WHSC1 in 503 ALL cases. Using Molecular Inversion Probe sequencing and breakpoint-spanning PCR we reliably detected alterations below 1% allele frequency. We identified 660...
Source: Haematologica - November 5, 2020 Category: Hematology Authors: Antić Ž, Yu J, Van Reijmersdal SV, Van Dijk A, Dekker L, Segerink WH, Sonneveld E, Fiocco M, Pieters R, Hoogerbrugge PM, Van Leeuwen FN, Van Kessel AG, Waanders E, Kuiper RP Tags: Haematologica Source Type: research

Serum monoclonal component in chronic lymphocytic leukemia: baseline correlations and prognostic impact.
PMID: 33147939 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 5, 2020 Category: Hematology Authors: Mozas P, Pineyroa JA, Nadeu F, Magnano L, Rivero A, Rivas-Delgado A, Bataller A, Fabregat A, Gine E, Baumann T, Villamor N, Arostegui JI, Aymerich M, Lopez-Guillermo A, Campo E, Delgado J Tags: Haematologica Source Type: research

100-year-old Haematologica images: bothriocephalus and pernicious anemia.
PMID: 33131236 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 1, 2020 Category: Hematology Authors: Balduini CL Tags: Haematologica Source Type: research

Forward into the second century of Haematologica.
PMID: 33131237 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 1, 2020 Category: Hematology Authors: Rowe JM Tags: Haematologica Source Type: research

Finding erythroid stress progenitors: cell surface markers revealed.
PMID: 33131238 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 1, 2020 Category: Hematology Authors: Ji P Tags: Haematologica Source Type: research

COVID-19 and sickle cell disease.
PMID: 33131239 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 1, 2020 Category: Hematology Authors: Menapace LA, Thein SL Tags: Haematologica Source Type: research

A CD205-directed antibody drug conjugate - lymphoma precision oncology or sophisticated chemotherapy?
PMID: 33131240 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 1, 2020 Category: Hematology Authors: Rieke DT, Keller U Tags: Haematologica Source Type: research

Splenectomy for immune thrombocytopenia: the evolution and preservation of treatment.
PMID: 33131241 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 1, 2020 Category: Hematology Authors: Remiker A, Neunert C Tags: Haematologica Source Type: research

Transforming the major autoantibody site on ADAMTS13: spacer domain variants retaining von Willebrand factor cleavage activity.
PMID: 33131242 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 1, 2020 Category: Hematology Authors: Scully M Tags: Haematologica Source Type: research

A new drug for an old concept: aptamer to von Willebrand factor for prevention of arterial and microvascular thrombosis.
PMID: 33131243 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 1, 2020 Category: Hematology Authors: Veyradier A Tags: Haematologica Source Type: research

Genetic platelet depletion is superior in platelet transfusion compared to current models.
PMID: 33131266 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - November 1, 2020 Category: Hematology Authors: Salzmann M, Schrottmaier WC, Kral-Pointner JB, Mussbacher M, Volz J, Hoesel B, Moser B, Bleichert S, Morava S, Nieswandt B, Schmid JA, Assinger A Tags: Haematologica Source Type: research

Pituitary iron and factors predictive of fertility status in transfusion dependent thalassemia.
Abstract Not available. PMID: 33121232 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 29, 2020 Category: Hematology Authors: Singer ST, Fischer R, Allen I, Lal A, Vichinsky E, Yuan Q, Wang ZJ Tags: Haematologica Source Type: research

The IL1-IL1RAP axis plays an important role in the inflammatory leukemic niche that favors acute myeloid leukemia proliferation over normal hematopoiesis.
Abstract Upregulation of the plasma membrane receptor IL1RAP in Acute Myeloid Leukemia (AML) has been reported but its role in the context of the leukemic bone marrow niche is unclear. Here, we studied the signaling events downstream of IL1RAP in relation to leukemogenesis and normal hematopoiesis. High IL1RAP expression was associated with a leukemic GMP-like state, and knockdown of IL1RAP in AML reduced colony-forming capacity. Stimulation with IL1β resulted in the induction of multiple chemokines and an inflammatory secretome via the p38 MAPK and NFκB signaling pathways in IL1RAP-expressing AML cells...
Source: Haematologica - October 29, 2020 Category: Hematology Authors: De Boer B, Sheveleva S, Apelt K, Vellenga E, Mulder AB, Schuringa GH, Jacob J Tags: Haematologica Source Type: research

Recapitulation of erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I) identifies defects in differentiation and nucleolar abnormalities.
Abstract The investigation of inherited disorders of erythropoiesis has elucidated many of the principles underlying the production of normal red blood cells and how this is perturbed in human disease. Congenital Dyserythropoietic Anaemia type 1 (CDA-I) is a rare form of anaemia caused by mutations in two genes of unknown function: CDAN1 and CDIN1 (previously called C15orf41), whilst in some cases, the underlying genetic abnormality is completely unknown. Consequently, the pathways affected in CDA-I remain to be discovered. To enable detailed analysis of this rare disorder we have validated a culture system which ...
Source: Haematologica - October 29, 2020 Category: Hematology Authors: Scott C, Downes DJ, Brown JM, Beagrie R, Olijnik AA, Gosden M, Schwessinger R, Fisher CA, Rose A, Ferguson DJP, Johnson E, Hill QA, Okoli S, Renella R, Ryan K, Brand M, Hughes J, Roy NBA, Higgs DR, Babbs C, Buckle VJ Tags: Haematologica Source Type: research

Venetoclax plus bendamustine-rituximab or bendamustine-obinutuzumab in chronic lymphocytic leukemia: final results of a phase 1b study (GO28440).
In conclusion, addition of bendamustine to Ven-R/-G increased toxicity without apparent efficacy benefit. PMID: 33121235 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 29, 2020 Category: Hematology Authors: Stilgenbauer S, Morschhauser F, Wendtner CM, Cartron G, Hallek M, Eichhorst B, Kozloff MF, Giever T, Lozanski G, Jiang Y, Huang H, Pignataro DS, Schary W, Humphrey K, Mobasher M, Salles G Tags: Haematologica Source Type: research

Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria.
Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is characterised by complement-mediated intravascular hemolysis (IVH) due to absence of complement regulators CD55 and CD59 on affected erythrocytes. Danicopan is a first-in-class oral proximal, complement alternative pathway factor D (FD) inhibitor. Therapeutic FD inhibition was designed to control IVH and prevent C3-mediated extravascular hemolysis (EVH). In this open-label, phase 2, dose-finding trial, 10 untreated hemolytic PNH patients received danicopan monotherapy (100-200 mg thrice daily). Endpoints included change in lactate dehydrogenase (LDH) at day 28 ...
Source: Haematologica - October 29, 2020 Category: Hematology Authors: Risitano AM, Kulasekararaj AG, Lee JW, Maciejewski JP, Notaro R, Brodsky R, Huang M, Geffner M, Browett P Tags: Haematologica Source Type: research

< i > SF3B1 < /i > -mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation.
SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation. Haematologica. 2020 Oct 29;Online ahead of print:0 Authors: Pozzo F, Bittolo T, Tissino E, Vit F, Vendramini E, Laurenti L, D'Arena G, Olivieri J, Pozzato G, Zaja F, Chiarenza A, Di Raimondo F, Zucchetto A, Bomben R, Rossi FM, Del Poeta G, Dal Bo M, Gattei V Abstract Chronic lymphocytic leukemia (CLL) is characterized by a low CD20 expression, in part explained by an epigenetic-driven downregulation triggered by mutations of the NOTCH1 gene. In the present study, by taking advantage of...
Source: Haematologica - October 29, 2020 Category: Hematology Authors: Pozzo F, Bittolo T, Tissino E, Vit F, Vendramini E, Laurenti L, D'Arena G, Olivieri J, Pozzato G, Zaja F, Chiarenza A, Di Raimondo F, Zucchetto A, Bomben R, Rossi FM, Del Poeta G, Dal Bo M, Gattei V Tags: Haematologica Source Type: research

Use of the HLA-B leader to optimize cord-blood transplantation.
Abstract Cord-blood transplantation (CBT) can cure life-threatening blood disorders. The HLA-B leader affects the success of unrelated donor transplantation but its role in CBT is unknown. We tested the hypothesis that the HLA-B leader influences CBT outcomes in unrelated single-unit cord-blood transplants performed by Eurocord/European Blood and Marrow Transplant (EBMT) centers between 1990 and 2018 with data reported to Eurocord. Among 4822 transplants, 2178 had one HLA-B mismatch of which 1013 were HLA-A and HLA-DRB1-matched. The leader (M or T) was determined for each HLA-B allele in patients and units to defi...
Source: Haematologica - October 29, 2020 Category: Hematology Authors: Petersdorf EW, Gooley T, Volt F, Kenzey C, Madrigal A, McKallor C, Querol S, Rafii H, Rocha V, Tamouza R, Chabannon C, Ruggeri A, Gluckman E Tags: Haematologica Source Type: research

Antimicrobial resistance is a risk factor for mortality in adults with sickle cell disease.
Abstract Not available. PMID: 33121239 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 29, 2020 Category: Hematology Authors: Srisuwananukorn A, Han J, Raslan R, Gowhari M, Hussain F, Njoku F, Molokie RE, Gordeuk VR, Saraf SL Tags: Haematologica Source Type: research

Unusual survival of a twin with homozygous α < sup > 0 < /sup > -thalassemia due to Chimerism.
Unusual survival of a twin with homozygous α0-thalassemia due to Chimerism. Haematologica. 2020 Oct 29;Online ahead of print:0 Authors: Pang D, Shang X, Cai D, Yang F, Lu H, Cheng Y, Wei X, He F, Xu X Abstract Not available. PMID: 33124788 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 29, 2020 Category: Hematology Authors: Pang D, Shang X, Cai D, Yang F, Lu H, Cheng Y, Wei X, He F, Xu X Tags: Haematologica Source Type: research

Emerging epigenetic therapeutics for myeloid leukemia: modulating demethylase activity with ascorbate.
s MCM Abstract The past decade has seen a proliferation of drugs that target epigenetic pathways. Many of these drugs were developed to treat acute myeloid leukemia, a condition in which dysregulation of the epigenetic landscape is well established. While these drugs have shown promise, critical issues persist. Specifically, patients with the same mutations respond quite differently to treatment. This is true even with highly specific drugs that are designed to target the underlying oncogenic driver mutations. Furthermore, patients who do respond may eventually develop resistance. There is now evidence that epigen...
Source: Haematologica - October 22, 2020 Category: Hematology Authors: Das AB, Smith-Díaz CC, Vissers MCM Tags: Haematologica Source Type: research

Cell-specific expression of < i > Hfe < /i > determines the outcome of < i > Salmonella enterica < /i > serovar Typhimurium infection in mice.
Cell-specific expression of Hfe determines the outcome of Salmonella enterica serovar Typhimurium infection in mice. Haematologica. 2020 Oct 13;Online ahead of print: Authors: Nairz M, Metzendorf C, Vujic-Spasic M, Mitterstiller AM, Schroll A, Haschka D, Hoffmann A, Von Raffay L, Sparla R, Huck CW, Talasz H, Moser PL, Muckenthaler MU, Weiss G Abstract Mutations in HFE cause hereditary hemochromatosis type I hallmarked by increased iron absorption, iron accumulation in hepatocytes and iron deficiency in myeloid cells. HFE encodes an MHC-I like molecule, but its function in immune responses to infection...
Source: Haematologica - October 13, 2020 Category: Hematology Authors: Nairz M, Metzendorf C, Vujic-Spasic M, Mitterstiller AM, Schroll A, Haschka D, Hoffmann A, Von Raffay L, Sparla R, Huck CW, Talasz H, Moser PL, Muckenthaler MU, Weiss G Tags: Haematologica Source Type: research

Pediatric-inspired chemotherapy incorporating pegaspargase is safe and results in high rates of minimal residual disease negativity in adults up to age 60 with Philadelphia chromosome-negative acute lymphoblastic leukemia.
Abstract Administration of pediatric-inspired chemotherapy to adults up to age 60 with acute lymphoblastic leukemia (ALL) is challenging in part due to toxicities of asparaginase as well as myelosuppression. We conducted a multicenter phase II clinical trial (NCT01920737) investigating a pediatric-inspired regimen, based on the augmented arm of the Children's Cancer Group 1882 protocol, incorporating 6 doses of pegaspargase 2000 IU/m2, rationally synchronized to avoid overlapping toxicity with other agents. We treated 39 adults ages 20-60 years (median, 38 years) with newly-diagnosed ALL (n=31) or lymphoblastic ly...
Source: Haematologica - October 13, 2020 Category: Hematology Authors: Geyer MB, Ritchie EK, Rao AV, Vemuri S, Flynn J, Hsu M, Devlin SM, Roshal M, Gao Q, Shukla M, Salcedo JM, Maslak P, Tallman MS, Douer D, Park JH Tags: Haematologica Source Type: research

Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape.
rd J, Brun S, Drenou B, Mayeur-Rousse C, Okamba P, Dorvaux V, Tichionni M, Rose J, Rubio MT, Jacob MC, Raggueneau V, Preudhomme C, Saas P, Ferrand C, Adotevi O, Roumier C, Jardin F, Garnache-Ottou F, Renosi F Abstract Neoplasms involving plasmacytoid Dendritic Cells (pDCs) include Blastic pDC Neoplasms (BPDCN) and other pDC proliferations, where pDCs are associated with myeloid malignancies: most frequently Chronic MyeloMonocytic Leukemia (CMML) but also Acute Myeloid Leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDCs in pDC-AML, and their link with the CD34+ b...
Source: Haematologica - October 13, 2020 Category: Hematology Authors: Zalmaï L, Viailly PJ, Biichle S, Cheok M, Soret L, Angelot-Delettre F, Petrella T, Collonge-Rame MA, Seilles E, Geffroy S, Deconinck E, Daguindau E, Bouyer S, Dindinaud E, Baunin V, Le Garff-Tavernier M, Roos-Weil D, Wagner-Ballon O, Salaun V, Feuillard Tags: Haematologica Source Type: research

The survival impact of maintenance lenalidomide: an analysis of real-world data from the Canadian Myeloma Research Group national database.
PMID: 33054120 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 13, 2020 Category: Hematology Authors: Cherniawsky HM, Kukreti V, Reece D, Masih-Khan E, McCurdy A, Jimenez-Zepeda VH, Sebag M, Song K, White D, Stakiw J, LeBlanc R, Reiman A, Aslam M, Louzada M, Kotb R, Gul E, Atenafu E, Venner CP Tags: Haematologica Source Type: research

Zanubrutinib monotherapy for patients with treatment na ïve chronic lymphocytic leukemia and 17p deletion.
Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. Haematologica. 2020 Oct 13;Online ahead of print: Authors: Tam CS, Robak T, Ghia P, Kahl BS, Walker P, Janowski W, Simpson D, Shadman M, Ganly PS, Laurenti L, Opat S, Tani M, Ciepluch H, Verner E, Šimkovič M, Österborg A, Trněný M, Tedeschi A, Paik JC, Kuwahara SB, Feng S, Ramakrishnan V, Cohen A, Huang J, Hillmen P, Brown JR Abstract Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have ...
Source: Haematologica - October 13, 2020 Category: Hematology Authors: Tam CS, Robak T, Ghia P, Kahl BS, Walker P, Janowski W, Simpson D, Shadman M, Ganly PS, Laurenti L, Opat S, Tani M, Ciepluch H, Verner E, Šimkovič M, Österborg A, Trněný M, Tedeschi A, Paik JC, Kuwahara SB, Feng S, Ramakrishnan V, Cohen A, Huang J, H Tags: Haematologica Source Type: research

No association between < i > ECSIT < /i > germline mutations and hemophagocytic lymphohistiocytosis in natural killer/T-cell lymphoma.
No association between ECSIT germline mutations and hemophagocytic lymphohistiocytosis in natural killer/T-cell lymphoma. Haematologica. 2020 Oct 13;Online ahead of print: Authors: Ong SY, Lim JQ, Grigoropoulos N, Laurensia Y, Huang D, Chia BKH, Zhe DCM, Saraf SA, Cheng CL, Chuang WY, Kuo MC, Su YJ, Phipps C, Nagarajan C, Lee YS, Lung DTC, Shih LY, Goh YT, Lim ST, Ong CK PMID: 33054138 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 13, 2020 Category: Hematology Authors: Ong SY, Lim JQ, Grigoropoulos N, Laurensia Y, Huang D, Chia BKH, Zhe DCM, Saraf SA, Cheng CL, Chuang WY, Kuo MC, Su YJ, Phipps C, Nagarajan C, Lee YS, Lung DTC, Shih LY, Goh YT, Lim ST, Ong CK Tags: Haematologica Source Type: research

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when and for whom?
Abstract Treatment discontinuation is considered one of the main goals of therapy for patients with chronic myeloid leukemia. Several criteria are felt to be necessary to consider discontinuation, while others may predict a better chance of achieving treatment-free remission. Criteria for discontinuation include patients in chronic phase chronic myeloid leukemia, a minimum duration of tyrosine kinase inhibitor therapy of 3 years, sustained deep molecular response for at least 2 years and a molecular response of at least MR4. In addition, proper education of the patient on the need for more frequent monitoring, pos...
Source: Haematologica - October 9, 2020 Category: Hematology Authors: Atallah E, Schiffer CA Tags: Haematologica Source Type: research

History of hematopoietic cell transplantation: challenges and progress.
Abstract After more than 60 years of research in allogeneic hematopoietic cell transplantation (HCT), this therapy has advanced from one that was declared dead in the 1960s to a standard treatment of otherwise fatal malignant and non-malignant blood diseases. To date, close to 1.5 million hematopoietic cell transplants have been performed in more than 1,500 transplantation centers worldwide. This review will highlight the enormous efforts by numerous investigators throughout the world who have brought the experimental field of HCT to clinical reality, examine ongoing challenges, and provide insights for the future...
Source: Haematologica - October 9, 2020 Category: Hematology Authors: Granot N, Storb R Tags: Haematologica Source Type: research

Differentiation therapy of myeloid leukemia: four decades of development.
Abstract Acute myeloid leukemia is characterized by arrested differentiation, and agents that overcome this block are therapeutically useful, as shown by the efficacy of all-trans retinoic acid in acute promyelocytic leukemia. However, the early promise of differentiation therapy did not translate into clinical benefit for other subtypes of acute myeloid leukemia, in which cytotoxic chemotherapeutic regimens remained the standard of care. Recent advances, including insights from sequencing of acute myeloid leukemia genomes, have led to the development of targeted therapies, comprising agents that induce differenti...
Source: Haematologica - October 9, 2020 Category: Hematology Authors: Madan V, Koeffler HP Tags: Haematologica Source Type: research

Characterization and evolutionary origin of novel C < sub > 2 < /sub > H < sub > 2 < /sub > zinc finger protein (ZNF648) required for both erythroid and megakaryocyte differentiation in humans.
Characterization and evolutionary origin of novel C2H2 zinc finger protein (ZNF648) required for both erythroid and megakaryocyte differentiation in humans. Haematologica. 2020 Oct 05;Online ahead of print: Authors: Ferguson DCJ, Mokim JH, Meinders M, Moody ERR, Williams TA, Cooke S, Trakarnsanga K, Daniels DE, Ferrer-Vicens I, Shoemark D, Tipgomut C, Macinnes KA, Wilson MC, Singleton BK, Frayne J Abstract Human ZNF648 is a novel poly C-terminal C2H2 zinc finger protein identified amongst the most dysregulated proteins in erythroid cells differentiated from iPSC. Its nuclear localisation and structure...
Source: Haematologica - October 5, 2020 Category: Hematology Authors: Ferguson DCJ, Mokim JH, Meinders M, Moody ERR, Williams TA, Cooke S, Trakarnsanga K, Daniels DE, Ferrer-Vicens I, Shoemark D, Tipgomut C, Macinnes KA, Wilson MC, Singleton BK, Frayne J Tags: Haematologica Source Type: research

Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration.
Abstract Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of patients with Hodgkin Transformation (HT) of CLL. Clinicobiologic characteristics, treatment type, and survival outcomes were analyzed and compared with historic case series. Ninety-four patients were identified. Median age at HT was 67 years (range, 38-85). Median time from CLL diagnosis to HT was 5.5 years (range, 0-20.2). Prior to HT, patients received a median of 2 therapies for CLL (range, 0-12). As init...
Source: Haematologica - October 5, 2020 Category: Hematology Authors: Stephens DM, Boucher K, Kander E, Parikh SA, Parry EM, Shadman M, Pagel JM, Cooperrider J, Rhodes J, Mato A, Winter A, Hill B, Gaballa S, Danilov A, Phillips T, Brander DM, Smith SM, Davids M, Rogers K, Glenn MJ, Byrd JC Tags: Haematologica Source Type: research

Modulated expression of adhesion, migration and activation molecules may predict the degree of response in chronic lymphocytic leukemia patients treated with ibrutinib plus rituximab.
ini A PMID: 33054124 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 5, 2020 Category: Hematology Authors: Peragine N, De Propris MS, Intoppa S, Milani ML, Mariglia P, Mauro FR, Raponi S, Soddu S, Cuneo A, Rigolin GM, Del Giudice I, Foà R, Guarini A Tags: Haematologica Source Type: research

The < i > TMPRSS6 < /i > variant (SNP rs855791) affects iron metabolism and oral iron absorption - a stable iron isotope study in Taiwanese women.
The TMPRSS6 variant (SNP rs855791) affects iron metabolism and oral iron absorption - a stable iron isotope study in Taiwanese women. Haematologica. 2020 Oct 05;Online ahead of print: Authors: Buerkli S, Pei SN, Hsiao SC, Lee CT, Zeder C, Zimmermann MB, Moretti D Abstract Genome wide studies have associated TMPRSS6 rs855791 (2321 C>T) with iron status and hepcidin. It is unclear whether this polymorphism affects iron absorption. In nonanemic Taiwanese women (n=79, 44 TT variant, 35 CC variant), we administered standardized rice-based test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on al...
Source: Haematologica - October 5, 2020 Category: Hematology Authors: Buerkli S, Pei SN, Hsiao SC, Lee CT, Zeder C, Zimmermann MB, Moretti D Tags: Haematologica Source Type: research

Standardization of flow cytometric minimal residual disease assessment in international clinical trials - a feasibility study from the European Myeloma Network.
Velden VHJ PMID: 33054135 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 5, 2020 Category: Hematology Authors: Op Bruinink DH, Oliva S, Rihova L, Schmitz A, Gilestro M, Te Marvelde J, Kralova R, Høholt H, Broijl A, Johnsen HE, Hajek R, Boccadoro M, Sonneveld P, Omedè P, Van der Velden VHJ Tags: Haematologica Source Type: research

SARS-CoV-2 severity in african americans - A role for Duffy Null?
PMID: 33054139 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 5, 2020 Category: Hematology Authors: Hebbel RP, Vercellotti GM Tags: Haematologica Source Type: research

Platelet proteome and function in X-linked thrombocytopenia with thalassemia and < i > in silico < /i > comparisons with gray platelet syndrome.
Platelet proteome and function in X-linked thrombocytopenia with thalassemia and in silico comparisons with gray platelet syndrome. Haematologica. 2020 Sep 28;Online ahead of print: Authors: Bergemalm D, Ramström S, Kardeby C, Hultenby K, Eremo AG, Sihlbom C, Bergström J, Palmblad J, Åström M Abstract In X-linked thrombocytopenia with thalassemia (XLTT; OMIM 314050), caused by the mutation p.R216Q in exon 4 of the GATA1 gene, male hemizygous patients display macrothrombocytopenia, bleeding diathesis and a β-thalassemia trait. Herein, we describe findings in two unrelated Swed...
Source: Haematologica - September 28, 2020 Category: Hematology Authors: Bergemalm D, Ramström S, Kardeby C, Hultenby K, Eremo AG, Sihlbom C, Bergström J, Palmblad J, Åström M Tags: Haematologica Source Type: research

Engineered type 1 regulatory T cells designed for clinical use kill primary pediatric acute myeloid leukemia cells.
Abstract Type 1 regulatory (Tr1) T cells induced by enforced expression of IL-10 (LV-10) are being developed as a novel treatment for chemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft vs host disease while mediating graft vs leukemia (GvL) effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptiona...
Source: Haematologica - September 28, 2020 Category: Hematology Authors: Cieniewicz B, Uyeda MJ, Chen PP, Sayitoglu EC, Liu JM, Andolfi G, Greenthal K, Bertaina A, Gregori S, Bacchetta R, Lacayo NJ, Cepika AM, Roncarolo MG Tags: Haematologica Source Type: research

Benefit of intermediate-dose cytarabine containing induction in molecular subgroups of acute myeloid leukemia.
PMID: 33054134 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - September 28, 2020 Category: Hematology Authors: Wei H, Zhou C, Lin D, Liu B, Li Y, Zhao X, Wei S, Gong B, Liu K, Gong X, Liu Y, Zhang G, Chen J, Zhang J, Jin J, Qiu S, Gu R, Wang Y, Mi Y, Wang J Tags: Haematologica Source Type: research

Pathogenetic and clinical study of a patient with thrombocytopenia due to the p.E527K gain-of-function variant of SRC.
PMID: 33054137 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - September 28, 2020 Category: Hematology Authors: Barozzi S, Di Buduo CA, Marconi C, Bozzi V, Seri M, Romano F, Balduini A, Pecci A Tags: Haematologica Source Type: research

Targeting shear gradient activated von Willebrand factor by the novel single-chain antibody A1 reduces occlusive thrombus formation in vitro.
Abstract Intraluminal thrombus formation precipitates conditions such as acute myocardial infarction and disturbs local blood flow resulting in areas of rapidly changing blood flow velocities and steep gradients of blood shear rate. Shear rate gradients are known to be pro-thrombotic with an important role for the shear-sensitive plasma protein von Willebrand factor (VWF). Here, we developed a single-chain antibody (scFv) that targets a shear gradient specific conformation of VWF to specifically inhibit platelet adhesion at sites of SRGs but not in areas of constant shear. Microfluidic flow channels with stenotic ...
Source: Haematologica - September 21, 2020 Category: Hematology Authors: Hoefer T, Rana A, Niego B, Jagdale S, Albers HJ, Gardiner EE, Andrews RK, Van der Meer AD, Hagemeyer CE, Westein E Tags: Haematologica Source Type: research