Kooperativer Bibliotheksverbund

In: Leukemia, Springer Science and Business Media LLC, Vol. 37, No. 2 ( 2023-02), p. 339-347

Abstract: Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes ( BIRC3 , EGR2 , MYD88, NFKBIE , NOTCH1 , POT1 , SF3B1, TP53 , and XPO1 ) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53 , BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-022-01802-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2008023-2

In: Neurology, Psychiatry and Brain Research, Elsevier BV, Vol. 22, No. 1 ( 2016-03), p. 13-

Type of Medium: Online Resource

ISSN: 0941-9500

URL: Article

DOI: 10.1016/j.npbr.2015.12.029

Language: English

Publisher: Elsevier BV

Publication Date: 2016

detail.hit.zdb_id: 2611131-7

In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-6-2)

Abstract: Analyzing liquid biopsies for tumor-specific aberrations can facilitate detection of measurable residual disease (MRD) during treatment and at follow-up. In this study, we assessed the clinical potential of using whole-genome sequencing (WGS) of lymphomas at diagnosis to identify patient-specific structural (SVs) and single nucleotide variants (SNVs) to enable longitudinal, multi-targeted droplet digital PCR analysis (ddPCR) of cell-free DNA (cfDNA). Methods In 9 patients with B-cell lymphoma (diffuse large B-cell lymphoma and follicular lymphoma), comprehensive genomic profiling at diagnosis was performed by 30X WGS of paired tumor and normal specimens. Patient-specific multiplex ddPCR (m-ddPCR) assays were designed for simultaneous detection of multiple SNVs, indels and/or SVs, with a detection sensitivity of 0.0025% for SV assays and 0.02% for SNVs/indel assays. M-ddPCR was applied to analyze cfDNA isolated from serially collected plasma at clinically critical timepoints during primary and/or relapse treatment and at follow-up. Results A total of 164 SNVs/indels were identified by WGS including 30 variants known to be functionally relevant in lymphoma pathogenesis. The most frequently mutated genes included KMT2D , PIM1 , SOCS1 and BCL2 . WGS analysis further identified recurrent SVs including t(14;18)(q32;q21) ( IGH::BCL2 ), and t(6;14)(p25;q32) ( IGH::IRF4 ). Plasma analysis at diagnosis showed positive circulating tumor DNA (ctDNA) levels in 88% of patients and the ctDNA burden correlated with baseline clinical parameters (LDH and sedimentation rate, p-value & lt;0.01). While clearance of ctDNA levels after primary treatment cycle 1 was observed in 3/6 patients, all patients analyzed at final evaluation of primary treatment showed negative ctDNA, hence correlating with PET-CT imaging. One patient with positive ctDNA at interim also displayed detectable ctDNA (average variant allele frequency (VAF) 6.9%) in the follow-up plasma sample collected 2 years after final evaluation of primary treatment and 25 weeks before clinical manifestation of relapse. Conclusion In summary, we demonstrate that multi-targeted cfDNA analysis, using a combination of SNVs/indels and SVs candidates identified by WGS analysis, provides a sensitive tool for MRD monitoring and can detect lymphoma relapse earlier than clinical manifestation.

Type of Medium: Online Resource

ISSN: 2234-943X

URL: Article

URL: Article

URL: Article

URL: Article

URL: Article

URL: Article

URL: Article

URL: Article

URL: Article

DOI: 10.3389/fonc.2023.1176698

DOI: 10.3389/fonc.2023.1176698.s001

DOI: 10.3389/fonc.2023.1176698.s002

DOI: 10.3389/fonc.2023.1176698.s003

DOI: 10.3389/fonc.2023.1176698.s004

DOI: 10.3389/fonc.2023.1176698.s005

DOI: 10.3389/fonc.2023.1176698.s006

DOI: 10.3389/fonc.2023.1176698.s007

DOI: 10.3389/fonc.2023.1176698.s008

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2023

detail.hit.zdb_id: 2649216-7

In: Leukemia, Springer Science and Business Media LLC, Vol. 37, No. 2 ( 2023-02), p. 504-504

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-023-01813-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2008023-2

In: Leukemia, Springer Science and Business Media LLC, Vol. 37, No. 3 ( 2023-03), p. 550-559

Abstract: Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance largely determine the outcome for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment remain to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using mass spectrometry-based in-depth proteomics. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients.

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-022-01796-7

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2008023-2

In: Blood, American Society of Hematology, Vol. 128, No. 23 ( 2016-12-08), p. 2666-2670

Abstract: We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBε, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia ( & lt;2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary central nervous system lymphoma (3% to 4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases [22.7%]) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases [27.3%] ). NFKBIE-deleted PMBL patients were more often therapy refractory (P = .022) and displayed inferior outcome compared with wild-type patients (5-year survival, 59% vs 78%; P = .034); however, they appeared to benefit from radiotherapy (P = .022) and rituximab-containing regimens (P = .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P = .003) and when restricting the analysis to immunochemotherapy-treated patients (P = .008). Whole-exome sequencing and gene expression profiling verified the importance of NF-κB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2016-03-704528

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood Advances, American Society of Hematology, Vol. 5, No. 3 ( 2021-02-9), p. 900-912

Abstract: Relapse is the leading cause of death of adult and pediatric patients with acute myeloid leukemia (AML). Numerous studies have helped to elucidate the complex mutational landscape at diagnosis of AML, leading to improved risk stratification and new therapeutic options. However, multi–whole-genome studies of adult and pediatric AML at relapse are necessary for further advances. To this end, we performed whole-genome and whole-exome sequencing analyses of longitudinal diagnosis, relapse, and/or primary resistant specimens from 48 adult and 25 pediatric patients with AML. We identified mutations recurrently gained at relapse in ARID1A and CSF1R, both of which represent potentially actionable therapeutic alternatives. Further, we report specific differences in the mutational spectrum between adult vs pediatric relapsed AML, with MGA and H3F3A p.Lys28Met mutations recurrently found at relapse in adults, whereas internal tandem duplications in UBTF were identified solely in children. Finally, our study revealed recurrent mutations in IKZF1, KANSL1, and NIPBL at relapse. All of the mentioned genes have either never been reported at diagnosis in de novo AML or have been reported at low frequency, suggesting important roles for these alterations predominantly in disease progression and/or resistance to therapy. Our findings shed further light on the complexity of relapsed AML and identified previously unappreciated alterations that may lead to improved outcomes through personalized medicine.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2020003709

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 2876449-3

In: Blood Advances, American Society of Hematology, Vol. 7, No. 12 ( 2023-06-27), p. 2794-2806

Abstract: Patients with chronic lymphocytic leukemia (CLL) progressing on ibrutinib constitute an unmet need. Though Bruton tyrosine kinase (BTK) and PLCG2 mutations are associated with ibrutinib resistance, their frequency and relevance to progression are not fully understood. In this multicenter retrospective observational study, we analyzed 98 patients with CLL on ibrutinib (49 relapsing after an initial response and 49 still responding after ≥1 year of continuous treatment) using a next-generation sequencing (NGS) panel (1% sensitivity) comprising 13 CLL-relevant genes including BTK and PLCG2. BTK hotspot mutations were validated by droplet digital polymerase chain reaction (ddPCR) (0.1% sensitivity). By integrating NGS and ddPCR results, 32 of 49 relapsing cases (65%) carried at least 1 hotspot BTK and/or PLCG2 mutation(s); in 6 of 32, BTK mutations were only detected by ddPCR (variant allele frequency [VAF] 0.1% to 1.2%). BTK/PLCG2 mutations were also identified in 6 of 49 responding patients (12%; 5/6 VAF & lt;10%), of whom 2 progressed later. Among the relapsing patients, the BTK-mutated (BTKmut) group was enriched for EGR2 mutations, whereas BTK-wildtype (BTKwt) cases more frequently displayed BIRC3 and NFKBIE mutations. Using an extended capture-based panel, only BRAF and IKZF3 mutations showed a predominance in relapsing cases, who were enriched for del(8p) (n = 11; 3 BTKwt). Finally, no difference in TP53 mutation burden was observed between BTKmut and BTKwt relapsing cases, and ibrutinib treatment did not favor selection of TP53-aberrant clones. In conclusion, we show that BTK/PLCG2 mutations were absent in a substantial fraction (35%) of a real-world cohort failing ibrutinib, and propose additional mechanisms contributing to resistance.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2022008821

Language: English

Publisher: American Society of Hematology

Publication Date: 2023

detail.hit.zdb_id: 2876449-3

In: Genes, Chromosomes and Cancer, Wiley, Vol. 61, No. 1 ( 2022-01), p. 27-36

Abstract: Formalin‐fixed, paraffin‐embedded (FFPE) specimens are an underutilized resource in medical research, particularly in the setting of transcriptome sequencing, as RNA from these samples is often degraded. We took advantage of an exome capture‐based RNA‐sequencing protocol to explore global gene expression in paired fresh–frozen (FF) and FFPE samples from 16 diffuse large B‐cell lymphoma (DLBCL) patients. While FFPE samples generated fewer mapped reads compared to their FF counterparts, these reads captured the same library complexity and had a similar number of genes expressed on average. Furthermore, gene expression demonstrated a high correlation when comparing housekeeping genes only or across the entire transcriptome ( r  = 0.99 for both comparisons). Differences in gene expression were primarily seen in lowly expressed genes and genes with small or large coding sequences. Using cell‐of‐origin classifiers and clinically relevant gene expression signatures for DLBCL, FF, and FFPE samples from the same biopsy paired nearly perfectly in clustering analysis. This was further confirmed in a validation cohort of 50 FFPE DLBCL samples. In summary, we found the biological differences between tumors to be far greater than artifacts created as a result of degraded RNA. We conclude that exome capture transcriptome sequencing data from archival samples can confidently be used for cell‐of‐origin classification of DLBCL samples.

Type of Medium: Online Resource

ISSN: 1045-2257 , 1098-2264

URL: Issue

URL: Article

DOI: 10.1002/gcc.v61.1

DOI: 10.1002/gcc.23002

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 1018988-9

detail.hit.zdb_id: 1492641-6

SSG: 12

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2617-2617

Abstract: The mutational status of the immunoglobuin heavy variable (IGHV) genes is an undisputable strong prognostic factor that subdivides patients with chronic lymphocytic leukemia (CLL) into 2 subgroups, i.e. IGHV-unmutated CLL (U-CLL) and IGHV-mutated CLL (M-CLL). U-CLL and M-CLL have distinct landscapes of genomic aberrations as well as distinct prognosis, since U-CLL is considerably more aggressive than M-CLL. That said, there is considerable clinical heterogeneity among M-CLL patients, ranging from patients without need of treatment to patients requiring early therapeutic intervention, indicating the need to further refine prognosis in this subgroup. In recent years, it has become evident that the prognostic impact of genomic aberrations may differ depending on IGHV gene mutational status. Hence, defining genomic aberrations with prognostic impact in M-CLL patients may help identifying patients with an predicted unfavorable prognosis within this subgroup, with obvious implications for management of follow up and therapy choice. To study the clinical impact of recurrent gene mutations in relation to IGHV gene mutational status, we collected a large, multi-center cohort including 4,674 patients with CLL [median age at diagnosis, 64.5 years; male/female, n=2,962 (63%)/n=1,712 (37%); Binet stage A (n=3,369, 74%), B (n=827, 18%), and C (n=387, 8%); IGHV-mutated (M-CLL, n=2,498, 56%) and IGHV-unmutated (U-CLL, n=1,927, 44%); isolated del(13q) (n=1,868, 41%), trisomy 12 (n=571, 13%), del(11q) (n=503, 11%), and del(17p) (n=249, 5.5%); treated (n=2,745, 59%) and untreated (n=1,929, 41%)] and performed next-generation sequencing (NGS) and/or Sanger sequencing of 9 genes (BIRC3, EGR2, NFKBIE, MYD88, NOTCH1, POT1, SF3B1, TP53, and XPO1) on pre-treatment samples. Overall, pathogenic mutations in any of these genes were detected in 1720/4674 patients (36.8%, using a variant allele frequency cutoff of 5% for NGS), while the remaining patients were wildtype; 2 mutations were observed in 361 patients (7.7%) and 3 or more mutations in 58 patients (1.2%). The mutation frequency for the individual genes was: TP53 (10.4%, including TP53 mutations and/or del(17p)), NOTCH1 (10.1%, 3'UTR mutations not included), SF3B1 (9.3%), XPO1 (3.9%), POT1 (3.8%), NFKBIE (3.7%), BIRC3 (3.0%), EGR2 (2.5%) and MYD88 (2.5%; Figure 1A). Except for MYD88, gene mutations in each of the investigated genes were associated with significantly shorter time-to-first-treatment (TTFT) in univariate analysis. In multivariate analysis of Binet stage A patients (n=3,369; including all genes, IGHV gene mutational status, age at diagnosis and gender), SF3B1 (Hazard Ratio (HR) 1.79; p & lt;0.001) , BIRC3 mutations (HR 1.50; p=0.004), XPO1 (HR 1.29; p=0.020), EGR2 (HR 1.42; p=0.021) and TP53 aberrations (HR 1.21; p=0.028), along with unmutated IGHV genes (HR 4.21; p & lt;0.001) and male gender (HR 1.12; p=0.027) remained as independent factors for shorter TTFT. In a multivariate model focusing on M-CLL Binet stage A patients (n=2,049), SF3B1 (HR 2.72; p & lt;0.001), NOTCH1 (HR 1.65; p=0.006), XPO1 (HR 2.21; p=0.021) and NFKBIE mutations (HR 1.74; p=0.025) were independent markers of poor TTFT (Figure 1B), while conversely in U-CLL Binet stage A cases (n=1157), SF3B1 mutations (HR 1.49; p & lt;0.001), TP53 aberrations (HR 1.30; p=0.011), BIRC3 mutations (HR 1.49; p=0.016) and male gender (HR 1.20; p=0.012) were significant factors for shorter TTFT (Figure 1C). In summary, different spectra of genetic mutations independently predicted short TTFT in M-CLL and U-CLL, respectively, with SF3B1 mutations as the only aberration found to be significant predictor of shorter time to first treatment in both subgroups. Importantly, mutations within several genes (i.e. SF3B1, NOTCH1, XPO1 and NFKBIE) identified patients in the M-CLL subgroup with a high-risk profile; conversely, TP53 mutations did not affect TTFT in this subgroup. On these grounds, we suggest to include analysis of recurrent gene mutations to identify high-risk patients within the M-CLL subgroup. Figure 1 Figure 1. Disclosures Brieghel: AstraZeneca: Consultancy. Rossi: Janssen: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Verastem: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Cellestia: Honoraria, Research Funding. Scarfo: Astra Zeneca: Honoraria; Abbvie: Honoraria; Janssen: Honoraria, Other: Travel grants. Mattsson: Gilead: Research Funding. Baliakas: Janssen: Honoraria; Gilead: Honoraria, Research Funding; Abbvie: Honoraria. Martinez-Lopez: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. de la Serna: AbbVie, AstraZeneca, Beigene, Gilead, GSK, Janssen, Jazzpharma, Novartis, Roche: Consultancy; ABBVIE, ASTRAZENECA,ROCHE: Research Funding; AbbVie, AstraZeneca, Roche: Speakers Bureau. Hernández Rivas: Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Smedby: Jansen-Cilag: Other: part of a research collaboration between Karolinska Institutet and Janssen Pharmaceutica NV for which Karolinska Institutet has received grant support. Bullinger: Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Gilead: Consultancy; Daiichi Sankyo: Consultancy, Honoraria; Hexal: Consultancy; Janssen: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Menarini: Consultancy; Novartis: Consultancy, Honoraria; Amgen: Honoraria; Astellas: Honoraria; Sanofi: Honoraria; Seattle Genetics: Honoraria; Bayer: Research Funding. Bosch: TAKEDA: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel. Terol: BMS: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Roche: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Hospital Clinico Valencia: Current Employment. Cuneo: AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Gaidano: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Niemann: Novo Nordisk Foundation: Research Funding; CSL Behring, Genmab, Takeda, Octapharma: Consultancy; Abbvie, AstraZeneca, Janssen: Consultancy, Research Funding. Ghia: Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Sunesis: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; ArQule/MSD: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Celgene/Juno/BMS: Consultancy, Honoraria; Gilead: Consultancy, Research Funding. Rosenquist: Roche: Honoraria; Janssen: Honoraria; Illumina: Honoraria; AstraZeneca: Honoraria; Abbvie: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-150648

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

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detail.hit.zdb_id: 80069-7