Kooperativer Bibliotheksverbund

In: Nature Genetics, Springer Science and Business Media LLC, Vol. 39, No. 3 ( 2007-03), p. 347-351

Type of Medium: Online Resource

ISSN: 1061-4036 , 1546-1718

URL: Article

DOI: 10.1038/ng1975

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2007

detail.hit.zdb_id: 1494946-5

SSG: 12

In: Nature Genetics, Springer Science and Business Media LLC, Vol. 39, No. 4 ( 2007-4), p. 567-567

Type of Medium: Online Resource

ISSN: 1061-4036 , 1546-1718

URL: Article

DOI: 10.1038/ng0407-567a

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2007

detail.hit.zdb_id: 1494946-5

SSG: 12

In: Journal of Clinical Investigation, American Society for Clinical Investigation, Vol. 119, No. 6 ( 2009-6-1), p. 1727-1740

Type of Medium: Online Resource

ISSN: 0021-9738

URL: Article

URL: Article

DOI: 10.1172/JCI37127

DOI: 10.1172/JCI37127DS1

Language: English

Publisher: American Society for Clinical Investigation

Publication Date: 2009

detail.hit.zdb_id: 2018375-6

In: Bioinformatics, Oxford University Press (OUP), Vol. 25, No. 6 ( 2009-03-15), p. 722-728

Abstract: Motivation: DNA copy number aberration—both inherited and sporadic—is a significant contributor to a variety of human diseases. Copy number characterization is therefore an area of intense research. Probe hybridization-based arrays are important tools used to measure copy number in a high-throughput manner. Results: In this article, we present a simple but powerful nonparametric rank-based approach to detect deletions and gains from raw array copy number measurements. We use three different rank-based statistics to detect three separate molecular phenomena—somatic lesions, germline deletions and germline gains. The approach is robust and rigorously grounded in statistical theory, thereby enabling the meaningful assignment of statistical significance to each putative aberration. We demonstrate the flexibility of our approach by applying it to data from three different array platforms. We show that our method compares favorably with established approaches by applying it to published well-characterized samples. Power simulations demonstrate exquisite sensitivity for array data of reasonable quality. Conclusions: Our flexible rank-based framework is suitable for multiple platforms including single nucleotide polymorphism arrays and array comparative genomic hybridization, and can reliably detect gains or losses of genomic DNA, whether inherited, de novo, or somatic. Availability: An R package RankCopy containing the methods described here, and is freely available from the author's web site (http://mendel.gene.cwru.edu/laframboiselab/). Contact:  Thomas.LaFramboise@case.edu Supplementary information:  Supplementary data are available at Bioinformatics online.

Type of Medium: Online Resource

ISSN: 1367-4811 , 1367-4803

URL: Article

DOI: 10.1093/bioinformatics/btp063

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2009

detail.hit.zdb_id: 1468345-3

SSG: 12

In: Cancer Letters, Elsevier BV, Vol. 239, No. 2 ( 2006-8), p. 227-233

Type of Medium: Online Resource

ISSN: 0304-3835

URL: Article

DOI: 10.1016/j.canlet.2005.08.007

Language: English

Publisher: Elsevier BV

Publication Date: 2006

detail.hit.zdb_id: 195674-7

detail.hit.zdb_id: 2004212-7

SSG: 12

In: Nature Medicine, Springer Science and Business Media LLC, Vol. 12, No. 7 ( 2006-07-01), p. 852-855

Type of Medium: Online Resource

ISSN: 1078-8956 , 1546-170X

URL: Article

DOI: 10.1038/nm1437

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2006

detail.hit.zdb_id: 1484517-9

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4605-4605

Abstract: The molecular pathogenesis of myeloid neoplasms characterized by 5q deletion (del(5q)) has not been completely elucidated. While some pathomorphologic features including e.g., megakaryocytic and erythroid dysplasia, have been associated with specific genes within minimal common deleted regions (CDR), genes responsible for clonal advantage and expansion have not been identified. It is not clear if haploinsufficiency of one or multiple genes within del(5q) is responsible for clonal evolution or whether mutations in those genes or other genes located in other genomic areas are present. Moreover, with the recognition of intra-tumor diversity and hierarchical clonal architecture, it may be possible to establish whether del(5q) or other lesions, including common somatic mutations, constitute the ancestral event in the pathophysiologic cascade. We performed a comprehensive mutational screen in 124 patients with del(5q), including 59 patients studied by whole exome sequencing (WES) and 65 by targeted deep NGS of genes within the deleted area and the other most commonly mutated genes as previously determined in WES cohorts. To identify pathogenic genes, those most consistently found to be haploinsufficient in del(5q) were matched for the presence of mutations in diploid cases. For the purpose of this study haploinsufficiency was quantitated based on the number of cases with del(5q) showing 〈 60% expression of the corresponding genes. E.g.,HDAC3 in 81%, PPP2CA in 62% and RPS14 in 14% of cases with del(5q). For all somatic mutations, we also describe the clonal composition based on deep sequencing in serial samples and analyses of variant allelic frequency. Finally, we compare the clonal size for individual mutations with that of del(5q). The latter was accomplished by calculation of clonal size based on allelic imbalance for informative SNPs present within deleted regions in heterozygous configurations in germ line samples. The average deviation from the ideal 50/50 distribution in tumor samples allowed for precise calculation of the proportion of cells in the sample affected by the deletion. Using this approach, there was a good correlation to the size of del(5q) clone by FISH (r=.94) Our results demonstrate that 10/14 genes were haploinsufficient within the CDR, but only 2 hemizygous somatic mutations were identified. However, 12 mutations in 7 genes (MATR3, SH3TC2, CSNK1A1, PDGFRB, CD74, FAT2 and G3BP1) were present with the area corresponding to the CDR in diploid cases. TP53 mutations were more commonly associated with del(5q) (73%, vs. 27% in diploid 5, p 〈 .001) and were particularly frequent in patients affected with 2 commonly retained regions (CRR1;5q11.1-5q14.2 and CRR2; 5q34-qter), where they were found in 81% of cases (30/37) vs. 19% (7/30) among CDR deletions (p 〈 .001). In lower-risk MDS, mutations were detected in 11% of deletion cases, whereas they were only found in 5% of diploid chr5 (p 〈 .0001). In higher-risk MDS, TP53 mutation were found in 42% of del(5q) vs. 4% of diploid chr5 (p 〈 .0001). Similarly, 45% patients with concomitant -7/del(7q) and del(5q) had TP53 mutations. The most common mutation associated with del(5q) was TP53, while mutations of FLT3, NRAS or TET2 were significantly mutually exclusive (p=0.03, 0.04 and 0.03; respectively). Next we determined the earliest somatic event by comparing of clonal size of the associated lesions. Del(5q) was present in 17-98% of tumor cells. We identified three theoretical possibilities as to the clonal architecture of del(5q) myeloid neoplasms: i) Tumors in which driver somatic mutations precede del(5q) (35%), ii) those in which del(5q) appears to precede any other somatic mutation (6%) and iii) the succession cannot be determined because of very expanded clones of similar size (“clonal saturation”) i.e., these cases were not informative. For cases in which del(5q) was a secondary lesion, TP53 was the ancestral event 64% of the time, and DNMT3A 27% of the time. The TP53 mutation was detected as a secondary event in 1 of 2 samples in which del(5q) was found to be ancestral. In sum, our results suggest that del(5q) is not universally an ancestral event. The TP53 mutation is the most common mutation in del(5q) and may also serve as ancestral event. While UPD17p and hemizygocity for TP53 can be found in 33% of TP53 mutant cases, most of the detected TP53 mutations were likely to heterozygous, and therefore the clonal size was not overestimated. Disclosures Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Corp: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim Corp: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.4605.4605

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 957-957

Abstract: Targeted and unbiased next generation sequencing (NGS) has contributed to a better understanding of the molecular pathogenesis of myeloid neoplasms, including MDS. Discovery efforts have identified novel classes of mutated genes, while deep NGS approaches have yielded a better appreciation of clonal hierarchy, inter-case variability and intra-tumor heterogeneity. MDS is a disease continuum characterized by a wide spectrum of often overlapping lesions that determine phenotype, while also serving as initiation and progression events. In addition to somatic lesions, germ line (GL) alterations can serve as bona fidenon-clonal ancestral events that play an underappreciated role in MDS pathogenesis. While some of these lesions are associated with childhood familial leukemia syndromes, others are unknown, and are likely characterized by a low/variable penetrance and delayed disease manifestation. To delineate clonal dynamics in MDS, we sequenced whole exomes of 262 cases with primary MDS and related disorders. For validation and confirmation we also deep sequenced a cohort of 1,686 additional cases with a various type of myeloid malignancies. An extensive bioanalytic pipeline and confirmatory sequencing, including GL DNA analysis, was used to discriminate somatic vs. GL lesions and exclude sequencing artifacts. Initially we focused on driver somatic events in significantly mutated genes. All somatic mutations were subjected to clonal hierarchy analysis using variant allele frequencies (VAFs). In selected cases (n = 180), serial analyses were performed. Using VAF rankings of each event, a position within the clonal hierarchy was assigned; while each patient has a single dominant clone, some may have a founding chromosomal abnormality and others may have VAFs too close to distinguish, i.e. have co-dominant events. In general, multiple subclonal events are detected in each patient. For the purpose of this analysis we distinguished between 2 types of ancestral events: 1) driver non-clonal mutations (e.g., GL TP53, RUNX1, ETV6) and 2) predisposition non-clonal events (FA genes, telomerase genes, BRCA1/2). The latter do not influence the clonal architecture. Based on average sequencing depth, 5,474 somatic mutations were identified: 241 (92%) were clonal dominant and 234 (89%) were sub-clonal (secondary) events. The median number of mutations in subclonal events per case was 13. The number of mutations in subclonal events was higher than that in events that were clonal dominant (4,881 vs 593). No genes were mutated in a purely dominant fashion and some genes were almost entirely subclonal, e.g., RAS and FLT3. For each dominant event, there is a frequent secondary lesion, e.g., dominant TET2 mutations are followed by subclonal second TET2 events, SRSF2 and ASXL1 lesions. Thus, novel relationships between dominant and subclone events were found, indicating the presence of invariant functional interactions among different mutations in MDS pathogenesis. In a confirmatory cohort studied by NGS targeted to a selected panel of significantly mutated genes, the number of subclonal events increased due to greater coverage and thus sensitivity. The spectrum of dominant events, however, should not differ as they are inherently associated with a high clonal burden. For examples, TP53 clonal mutations frequently co-occur with TP53 subclonal mutations (12%, p=.004), but are exclusive of STAG2 subclonal mutations. EZH2 clonal and ASXL1 secondary mutations also co-occur. Classifications of clonal and secondary events may have prognostic and diagnostic implications. We identified a spectrum of novel predisposition and non-clonal driver variants by comparing to ethnically weighted control populations. Eight mutations (3%, 8/262 cases) in 3 genes (DDX41, TP53, and ELANE) were identified as driver non-clonal mutations because identical mutations were reported in familial leukemia syndromes, while 16 mutations (6%) in 3 genes (CSF3R, BRCA1, and RPL5) were identified as non-clonal predisposition events. Detailed understanding of such clonal dynamics and complexity of clonal hierarchical complexity may have clinical significance, both for somatic mutations and for germline events. Increasing clonal burden of extracted genes associated with predictive prognostic impact should be prospectively validated in a more uniform and larger cohort of MDS cases. Disclosures Makishima: The Yasuda Medical Foundation: Research Funding. Mukherjee:Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding. Sole:Celgene: Membership on an entity's Board of Directors or advisory committees. Carraway:Celgene: Research Funding, Speakers Bureau; Baxalta: Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Ogawa:Kan research institute: Consultancy, Research Funding; Sumitomo Dainippon Pharma: Research Funding; Takeda Pharmaceuticals: Consultancy, Research Funding. Maciejewski:Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Speakers Bureau; Apellis Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.957.957

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 307-307

Abstract: Abstract 307 Whole-exome (WES) sequencing revealed tremendous mutational heterogeneity in leukemia. While WES can be applied for discovery, it also has potential as a diagnostic tool that can overcome the shortcomings of current methods. We theorized that, in addition to mutation discovery, systematic application of WES in MDS may reveal distinct mutational patterns allowing for new molecular classification. We performed WES in 116 paired exomes, including MDS (n=57), MDS/MPN (n=36), and sAML (n=23). We also included comparative analysis with pAML (N=202; TCGA), and other publicly available data for a total of 333 exomes; 10 patients were studied serially. Paired DNA (marrow/CD3+ cells) was subjected to WES, sequence-aligned by BW Aligner, and variants detected via GATK pipeline (Broad Institute). We used defined criteria to minimize false-positives: P 〈 .001 tumor/control, alterations ≥10% of total tumor reads, 〈 25% in germline, 〉 5% prevalence, and not found in ex/internal SNP databases. This narrowed the spectrum to 645 mutations (54 genes) for analysis with clinical/phenotypic correlations. Mutations were isolated or grouped by pathway, e.g., PRC2, cohesin complex, plexins and dyneins, etc. In MDS, examples of prevalent mutations include SF3B1 (14%), DNMT3A (11%) and U2AF1/2 (9%). In MDS/MPN: TET2 (36%), SRSF2 (22%) and ASXL1 (19%) and SETBP1 (6%); in sAML: NRAS/RAS (16%), RUNX1 (16%) and cohesin mutations (12%), in contrast to pAML with mutational spectrum dominated by FLT3, DNMT3A, NMP1 or SMC3/1A (cohesin complex). The exome panel did not cover 20% patients, suggesting that their pathogenesis may be related to less recurrent events (613 candidates: 2nd screening phase). When mutational spectrum of sAML vs pAML were compared, mutants of SF3B1 (7 vs 1%, P=.04), BCOR (7 vs 1%, P=.04), CDH11/23 (13 vs. 1%, P=.003), FMN2 (7 vs. 1%, P=.04), PPFIA2 (7% vs 0%, P=.01), SPTAN1 (7% vs 0%, P=.01) and VPS8 (7 vs 0%, P=.017) were more frequent in sAML while DNMT3A and NPM1 were less common. Analysis of MDS/MPN revealed mutations in PRC2 (2 vs 11%, P=.05), SRSF2 (5 vs. 22%, P=.010) and TET2 (3 vs. 33%, P 〈 .001) more frequent than in MDS. Mutations in SF3B1 were more recurrent in low/Int-1 IPSS categories compared to Int-2/high/sAML (21 vs. 3%, P=.01), in which mutations in N/KRAS (0 vs. 14%, P=.01) and TP53 (0 vs. 14%, P=.01) were more frequent. Functional group comparisons revealed that lesions in epigenetic (56 vs 23%, P=.001) and signal transduction genes (36 vs 9%, P=.001) were more prevalent in MDS/MPN compared to MDS in which they accumulated according to risk (high vs low: 36 vs 5%, P=.001 or 52% in pAML). Spliceosomal mutations were overrepresented in MDS/MPN vs MDS (58 vs 37%, P=.031), in sAML vs pAML (23 vs 9%, P=.032), and in low risk vs high risk cases (45 vs 22%, P=.02). Cytoskeleton organization gene mutations were overrepresented in sAML vs pAML (39 vs 13%, P=.001). TSG were more frequent in high-risk vs low-risk MDS (30 vs 5%, P=.003). Moreover, TET2 mutations coincided with SRSF2 and PRC2 mutations (P 〈 .001 and P=.010); DNMT3 mutations with SF3B1 and BCOR (P=.04 and P=.004); SRSF2 with ASXL1 (P=.017); RUNX1 with cohesin and BCOR (P=.003 and P=.04), CBL mutations with PRPF8 and ASXL1 (P=.04 or P=.003); TP53 with PRPF8 (P=.04). After analyzing survival impact of individual mutations, functional groups, cytogenetic category and clinical parameters, we found TP53, ETV6, PRPF8, FMN2, UMODL1, KIT, GATA2, complex karyotype and chr. 5 anomalies had a prognostic impact on OS. However, in multivariate analyses, the first variable to stratify our cohort was, as expected, the diagnosis subtype (HR 2.2, P 〈 .001), but also mutations in PRPF8 (HR 5.4, P=.004). In MDS and grouped MDS/MPN, significant variables included KIT (HR 12, P=.022) and TP53 mutations (HR 3.6, P=.045). Apart from traditional analyses, we also applied a recursive partitioning algorithm to construct an unbiased survival tree encompassing every mutation: e.g., PRPF8, CSMD1, U2AF2, IDH2, PPFIA2, SF3B1 and NRAS showed the highest difference in OS with this method. In sum, mutational spectrum of myeloid neoplasms can be assessed with WES. The pattern of frequency and concurrence in each diagnostic subtype differs substantially, a feature that can be exploited diagnostically. Despite heterogeneity, mutations and their combinations can be found to categorize patients and serve as prognostic markers. Analysis of additional cases is ongoing and will be presented at the meeting. Disclosures: Makishima: Scott Hamilton CARES Initiative: Research Funding. Maciejewski:NIH: Research Funding; Aplastic Anemia & MDS International Foundation: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V120.21.307.307

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4389-4389

Abstract: Different CSF3R mutations (CSF3RMT) result in aberrant G-CSF signaling pathways and are linked to a wide range of myeloid disorders. Loss-of-function mutations in its extracellular domain cause severe congenital neutropenia (SCN). Activating mutations in the juxtamembrane region have been associated with a variety of myeloid malignancies. Truncating mutations in the cytoplasmic domain are associated with SCN cases that progress to MDS or AML. In this study, we evaluate the extent to which different CSF3RMT associate with disease onset, progression to leukemia and neutrophil counts in patients (pts) diagnosed with myeloid malignancies. We identified CSF3RMT cases in a cohort of 1400 pts [median age 71 years (yrs)]. We analyzed somatic and germline mutational patterns, and cross-sectional correlation with other gene mutations in CSF3RMT. A stringent algorithm based on conserved amino acid residues and alterations of protein features was used to predict the pathogenic significance of CSF3RMT. We identified 44 CSF3RMT: 33 germline (CSF3RGL) and 11 somatic (CSF3RS) variants. Most CSF3RGL were found in pts (median age 63 yrs) with MDS or related conditions (87% of all mutant cases), conversely these mutations were present in 5% (n= 22/424) of MDS, 3% (n= 7/244) MDS/MPN and 〈 1% (n= 3/392) of AML and in 1 out of 3 pts with aCML tested. Mutations were mostly missense and located between the cytoplasmic (58%: M696T, R698C (isoform III), D732N, P733T, S744F, Y752*, E808K), and extracellular (42%: C131Y, E149Q, A208V, Q216H, D320N, E405K, S413L, Y562H) domains. No mutations were detected in the juxtamembrane domain. Variants were grouped in Tier-1 (61%: C131Y, E149Q, A208V, Q216H, D320N, E405K, S413L, Y562H Y752*, E808K) and Tier-2 (variants with uncertain significance, 39%: S413L, M696T, R689C, D732N, P733T, S744F). E808K and R698C were the most common amino acid changes in Tier-1 (53%) and Tier-2 (44%), respectively. A total of 4/7 pts with E808K progressed to AML (but none with R698C), supporting previous observations that E808K (or E785K) represents a pathogenic variant predisposing to leukemia. A total of 46% (n=14) of pts with CSF3RGL had neutropenia [median 0.9x109/L (0.02-1.22x109/L)] at the time of sampling. Two pts diagnosed with a prior cancer manifested sustained neutropenia before the diagnosis of MDS and MDS/MPN. G-CSF was administered in 21% of pts. Alterations in -7/7q- were common (21%). Some pts also harbored other somatic mutations in NF1 (15%), DNMT3A (12%), SETBP1 (12%), or U2AF1 (12%). Of note, 1 patient carried mutations in WAS and GATA2 and another carried a mutation in VPS45, which have been previously associated with SCN/MDS. The patient with aCML harbored also a CSF3RS (T615A). Overall combined allelic burden in pts cohort was 2% vs. 1.6% expected allelic burden in control populations for the same variants (P=.02). CSF3R S were found in 11 pts (median age 71 yrs) with AML or MDS related conditions (73% of all mutant cases), conversely these mutations were present in 1.4% (n= 6/424) of AML, 〈 1% in MDS (n= 2/244) and MDS/MPN (n= 1/392) and in 2/3 pts with aCML tested. Mutations were missense in 63% of pts, T618I being most recurrent (n=5/11; 45%). Frameshifts accounted for 36% of the mutations and were localized in the cytoplasmic domain (Q741*, Q749*, Y752*, Q768*). All mutations were heterozygous. At the time of sampling 3/11 pts had leukocytosis and 3/11 had neutropenia. Mutations were distributed between the juxtamembrane domain (55%) and the cytoplasmic domain (45%). Mutations in the extracellular domain were not detected. Pts with sAML mostly carried mutations in the juxtamembrane domain (67%), those with MDS carried only in cytoplasmic domain, and those with MDS/MPN or aCML carried mutations in both the juxtamembrane and extracellular domains. There was one somatic and one RUNX1GL mutation. The cytogenetic abnormalities -7/7q- were detected in 18% (2/11) of cases. Interestingly, T618I was found solely in pts with sAML. Focusing on associations between CSF3RMT and mutations in the class III receptor tyrosine kinases CSF1R, FLT3, and KIT we identified only FLT3 to be co-mutated with CSF3RMT. All 3 pts (2 CSF3RGL and 1 CSF3RS) with such co-mutations evolved to AML. In sum, we found that CSF3RGL do not commonly co-occur with CSF3RS, suggesting that the neutropenia observed at the sampling time most likely is causative of undetected GL variants and/or is representative of a long unrecognized disease. Disclosures Nazha: MEI: Consultancy. Carraway:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Jazz: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; FibroGen: Consultancy. Santini:Otsuka: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-116554

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7