Stephan Hütter
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View article: Solving Riddles Through Sequencing (SIRIUS): unlocking hematologic diagnoses by whole genome and transcriptome sequencing
Solving Riddles Through Sequencing (SIRIUS): unlocking hematologic diagnoses by whole genome and transcriptome sequencing Open
In the rapidly evolving field of hematology, the diagnosis of leukemias and lymphomas poses major challenges, despite significant genetic advancements. Although established diagnostic methods comprise a multidisciplinary approach and are c…
View article: MDS without clonal marker: When depth outperforms breadth
MDS without clonal marker: When depth outperforms breadth Open
Background: Myelodysplastic neoplasms (MDS) are a heterogeneous group of clonal myeloid neoplasms. The interplay of mutations shapes disease phenotype, progression, and response to therapy, highlighting clonality as a central feature of MD…
View article: The evolution to hepta-refractory myeloma involves sequential loss of CD38, BCMA and GPRC5D
The evolution to hepta-refractory myeloma involves sequential loss of CD38, BCMA and GPRC5D Open
Introduction: No other hematologic malignancy has seen more drug approvals than multiple myeloma (MM). Yet, MM remains largely incurable, even in the era of T-cell engaging therapies. Patients who have exhausted all treatment options can b…
View article: A Unifying Mechanism for Shared Splicing Aberrations in Splicing Factor Mutant Cancers
A Unifying Mechanism for Shared Splicing Aberrations in Splicing Factor Mutant Cancers Open
Cancer-associated splicing factor (SF) mutations in SF3B1 , U2AF1 , and SRSF2 induce distinct changes in alternative splicing (AS). Yet these mutations are strikingly mutually exclusive, pointing to a convergent downstream mechanism. We hy…
View article: IntegrateALL: an end-to-end RNA-seq analysis pipeline for multilevel data extraction and interpretable subtype classification in B-precursor ALL
IntegrateALL: an end-to-end RNA-seq analysis pipeline for multilevel data extraction and interpretable subtype classification in B-precursor ALL Open
Transcriptome sequencing (RNA-seq) is emerging as a diagnostic standard for B-cell precursor acute lymphoblastic leukemia (B-ALL). Expression-based classifiers reach ∼95% accuracy, but reproducible end-to-end solutions that also integrate …
View article: Telomere content and genomics of myeloid neoplasia by whole-genome sequencing
Telomere content and genomics of myeloid neoplasia by whole-genome sequencing Open
Telomere length shortening has been associated with genomic instability and acquisition of molecular lesions, but these processes have not been systematically studied across large cohorts of myeloid neoplasia (MN). As proof of concept for …
View article: Genetic Determinants of Hypercoagulability in Complement and Hemostatic Systems Shape the Thrombotic Risk of Paroxysmal Nocturnal Hemoglobinuria
Genetic Determinants of Hypercoagulability in Complement and Hemostatic Systems Shape the Thrombotic Risk of Paroxysmal Nocturnal Hemoglobinuria Open
Thrombotic events (TEs) are the main cause of morbimortality in PNH. Despite a monogenic etiology, PNH displays remarkable heterogeneity as to the hemolytic and thrombotic phenotypes, suggesting the influence of modifying factors. Compleme…
View article: Telomere Content Diversity in Myeloid Neoplasia Could Inform on Differential Sensitivity to Telomerase Inhibitors
Telomere Content Diversity in Myeloid Neoplasia Could Inform on Differential Sensitivity to Telomerase Inhibitors Open
The recent FDA approval of Imetelstat, a new class of antineoplastic drugs for the treatment of MDS1 opens the question on whether telomere content (TC) and/or telomerase function might constitute therapeutic targets and diagnostic biomark…
View article: Similarities and Differences of <i>DNMT3A</i>, <i>TET2</i> and <i>ASXL1</i> Mutations across Ccus, MDS and AML
Similarities and Differences of <i>DNMT3A</i>, <i>TET2</i> and <i>ASXL1</i> Mutations across Ccus, MDS and AML Open
Background: The most frequently mutated genes in clonal hematopoiesis (CH) occurring during aging are DNMT3A, TET2, and ASXL1 (DTA). DTA mutations (mut) also recurrently occur in overt myeloid malignancies. Aim: Analyze similarities and di…
View article: Two Ways to Complex Karyotype in MDS - the Role of Del(5q) and <i>TP53</i>
Two Ways to Complex Karyotype in MDS - the Role of Del(5q) and <i>TP53</i> Open
Background: Deletions (del) 5q in MDS typically occur either in MDS with low blasts and del(5q) (MDS-5q according to WHO) or in MDS with complex karyotype (CK). While MDS-5q are generally associated with a favorable prognosis and harbor TP…
View article: A high proportion of germline variants in pediatric chronic myeloid leukemia
A high proportion of germline variants in pediatric chronic myeloid leukemia Open
Chronic myeloid leukemia (CML) typically occurs in late adulthood. Pediatric CML is a rare form of leukemia. In all age groups, the characteristic genetic driver of the disease is the BCR::ABL1 fusion gene. However, additional genomic even…
View article: Interface-guided phenotyping of coding variants in the transcription factor RUNX1
Interface-guided phenotyping of coding variants in the transcription factor RUNX1 Open
Single-gene missense mutations remain challenging to interpret. Here, we deploy scalable functional screening by sequencing (SEUSS), a Perturb-seq method, to generate mutations at protein interfaces of RUNX1 and quantify their effect on ac…
View article: Proximally biased V(D)J recombination in the clonal evolution of IGH alleles in <i>KMT2A::AFF1</i> BCP‐ALL of all age classes
Proximally biased V(D)J recombination in the clonal evolution of IGH alleles in <i>KMT2A::AFF1</i> BCP‐ALL of all age classes Open
We report the analysis of 379 cases of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) using whole-transcriptome sequencing data (Table S1 and Supporting Information S1: Methods). In 48 adult, 36 pediatric, and 37 infant cases of B…
View article: Comparing malignant monocytosis across the updated WHO and ICC classifications of 2022
Comparing malignant monocytosis across the updated WHO and ICC classifications of 2022 Open
The World Health Organization (WHO) classification of hematolymphoid tumors and the International Consensus Classification (ICC) of 2022 introduced major changes to the definition of chronic myelomonocytic leukemia (CMML). To assess its qu…
View article: Parallel Genomic Analysis from Paired Bone Marrow and Peripheral Blood Samples of 200 Cytopenic Patients
Parallel Genomic Analysis from Paired Bone Marrow and Peripheral Blood Samples of 200 Cytopenic Patients Open
Background: Analysis of bone marrow is the gold standard in patients with unexplainable cytopenia for diagnosing (or excluding) myelodysplastic neoplasm (MDS). Besides morphology also molecular genetics and cytogenetics are currently asses…
View article: Modification of the ELN Classification 2022 Refines Risk Assessment in MDS/AML Patients
Modification of the ELN Classification 2022 Refines Risk Assessment in MDS/AML Patients Open
Background: The International Consensus Classification (ICC) introduced MDS/AML as a novel myeloid disease entity defined by 10-19% blasts in the absence of AML-defining recurrent genetic abnormalities. MDS/AML patients should be eligible …
View article: The clinical and genomic landscape of patients with <i>DDX41</i> variants identified during diagnostic sequencing
The clinical and genomic landscape of patients with <i>DDX41</i> variants identified during diagnostic sequencing Open
Deleterious germ line variants in DDX41 are a common cause of genetic predisposition to hematologic malignancies, particularly myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). Targeted next-generation sequencing was perfor…
View article: Characterization of myeloproliferative neoplasms based on genetics only and prognostication of transformation to blast phase
Characterization of myeloproliferative neoplasms based on genetics only and prognostication of transformation to blast phase Open
Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal disorders characterized by aberrant hematopoietic proliferation and an intrinsic risk of progression to blast phase. The WHO classification 2022 identifies chronic myel…
View article: Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy
Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy Open
Growth factor independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of hematopoiesis. GFI1-36N is a germ line variant, causing a change of serine (S) to asparagine (N) at position 36. We previously reported that t…
View article: Analysis of 3,760 hematologic malignancies reveals rare transcriptomic aberrations of driver genes
Analysis of 3,760 hematologic malignancies reveals rare transcriptomic aberrations of driver genes Open
Background Rare oncogenic driver events, particularly affecting the expression or splicing of driver genes, are suspected to substantially contribute to the large heterogeneity of hematologic malignancies. However, their identification rem…
View article: Interface-guided phenotyping of coding variants in the transcription factor RUNX1 with SEUSS
Interface-guided phenotyping of coding variants in the transcription factor RUNX1 with SEUSS Open
Understanding the consequences of single amino acid substitutions in cancer driver genes remains an unmet need. Perturb-seq provides a tool to investigate the effects of individual mutations on cellular programs. Here we deploy SEUSS, a Pe…