Fusion Genes in Myeloid Malignancies DOI Open Access
Chieh Hwee Ang, Hein Than,

Tertius Tuy

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 4055 - 4055

Published: Dec. 3, 2024

Fusion genes arise from gross chromosomal rearrangements and have been closely linked to oncogenesis. In myeloid malignancies, fusion play an integral role in the establishment of diagnosis prognostication. clinical management patients with acute leukemia, are deeply incorporated risk stratification criteria guide choice therapy. As a result their intrinsic ability define specific disease entities, oncogenic also immense potential be developed as therapeutic targets biomarkers. current era genomic medicine, breakthroughs innovation sequencing techniques led rise detection novel genes, concept standard-of-care diagnostics continues evolve this field. review, we outline molecular basis, mechanisms action impact genes. We discuss pros cons available methodologies that can used detect To contextualize challenges encountered practice pertaining diagnostic workup malignancies share our experience insights form three case studies.

Language: Английский

Combination therapy with novel agents for acute myeloid leukaemia: Insights into treatment of a heterogenous disease DOI Creative Commons
Wei‐Ying Jen, Hagop M. Kantarjian, Tapan M. Kadia

et al.

British Journal of Haematology, Journal Year: 2024, Volume and Issue: 205(1), P. 30 - 47

Published: May 9, 2024

Summary The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets triplets targeted immune therapies the focus numerous ongoing trials. development mutation‐targeted has greatly enhanced armamentarium, FLT3 inhibitors and isocitrate dehydrogenase improving outcomes frontline relapsed/refractory (RR) AML, menin showing efficacy RR NPM1 mut KMT2A ‐rearranged AML. With so many new drugs approved, number potential combinatorial approaches to leverage maximal benefit these agents increased dramatically, while at same time introducing clinical challenges, such as key preclinical data supporting therapy, how optimally combine sequence novel agents, optimise dose duration maintain safety enhancing efficacy, optimal therapy role measurable residual disease decision‐making both low‐intensity settings. In this review, we will outline evidence leading approval their on‐label current approvals they may be combined a safe deliverable fashion further improve

Language: Английский

Citations

19
Optical Genome Mapping for Cytogenetic Diagnostics in AML DOI Open Access
Verena Nilius‐Eliliwi, Wanda M. Gerding, Roland Schroers

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(6), P. 1684 - 1684

Published: March 9, 2023

The classification and risk stratification of acute myeloid leukemia (AML) is based on reliable genetic diagnostics. A broad expanding variety relevant aberrations are structural variants beyond single-nucleotide variants. Optical Genome Mapping an unbiased, genome-wide, amplification-free method for the detection In this review, current knowledge (OGM) with regard to diagnostics in hematological malignancies general, AML specific, summarized. Furthermore, review focuses ability OGM expand use cytogenetic perhaps even replace older techniques such as chromosomal-banding analysis, fluorescence situ hybridization, or copy number variation microarrays. Finally, compared amplification-based a brief outlook future directions given.

Language: Английский

Citations

27
A framework for the clinical implementation of optical genome mapping in hematologic malignancies DOI Creative Commons
Brynn Levy, Rashmi Kanagal‐Shamanna, Nikhil Sahajpal

et al.

American Journal of Hematology, Journal Year: 2024, Volume and Issue: 99(4), P. 642 - 661

Published: Jan. 2, 2024

Optical Genome Mapping (OGM) is rapidly emerging as an exciting cytogenomic technology both for research and clinical purposes. In the last 2 years alone, multiple studies have demonstrated that OGM not only matches diagnostic scope of conventional standard care testing but it also adds significant new information in certain cases. Since consolidates benefits costly laborious tests (e.g., karyotyping, fluorescence situ hybridization, chromosomal microarrays) a single cost-effective assay, many laboratories started to consider utilizing OGM. 2021, international working group early adopters who are experienced with routine patients hematological neoplasms formed consortium (International Consortium Hematologic Malignancies, henceforth "the Consortium") create consensus framework implementation setting. The focus provide guidance implementing three specific areas: validation, quality control analysis interpretation variants. complex variables, we felt by consolidating our collective experience, could practical useful tool uniform hematologic malignancies ultimate goal achieving globally accepted standards.

Language: Английский

Citations

16
Optical genome mapping improves the accuracy of classification, risk stratification, and personalized treatment strategies for patients with acute myeloid leukemia DOI
Sanam Loghavi, Qing Wei, Farhad Ravandi

et al.

American Journal of Hematology, Journal Year: 2024, Volume and Issue: 99(10), P. 1959 - 1968

Published: July 17, 2024

Abstract Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision‐making. We examined clinical utility optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed 56 refractory/relapsed), all whom also underwent chromosomal banding analysis (CBA), fluorescence situ hybridization, targeted next‐generation sequencing. OGM detected nearly clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided clonal burden was above 20%. additional cytogenomic aberrations and/or information on fusion genes 77 (48%) patients, including eight normal karyotypes four failed karyotyping. The most common alterations by included chromoanagenesis ( n = 23), KMT2A partial tandem duplication 11), rearrangements involving MECOM 7), NUP98 2), JAK2 other gene fusions 17 10 showing novel partners. pinpointed (11%) where were concurrently CBA. Overall, 24 (15%) exclusively had potential to alter classification, stratification, trial eligibility. emerges as a powerful tool identifying detecting subtle or cryptic may otherwise remain undetectable

Language: Английский

Citations

11
Optical Genome Mapping as an Alternative to FISH-Based Cytogenetic Assessment in Chronic Lymphocytic Leukemia DOI Open Access

Andriana Valkama,

Sandra Vorimo, Timo A. Kumpula

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1294 - 1294

Published: Feb. 17, 2023

The fluorescence in situ hybridization (FISH) technique plays an important role the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide analysis, FISH needs to be complemented other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, this is often not feasible a diagnostic setup. Optical genome mapping (OGM) novel for high-resolution detection structural variants (SVs), previous studies have indicated that OGM could serve as generic tool hematological malignancies. Herein, we report results from our study evaluating concordance standard-of-care 18 CLL samples. were fully concordant between these two techniques blinded comparison. Using silico dilution series, lowest limit was determined range 3 9% variant allele fractions. Genome-wide analysis by revealed additional (>1 Mb) aberrations 78% samples, both unbalanced balanced SVs. Importantly, also enabled clinically relevant complex karyotypes, undetectable FISH, three Overall, demonstrates potential first-tier test powerful SV analysis.

Language: Английский

Citations

21
Feasibility of Optical Genome Mapping in Cytogenetic Diagnostics of Hematological Neoplasms: A New Way to Look at DNA DOI Creative Commons
Nicoletta Coccaro, Luisa Anelli, Antonella Zagaria

et al.

Diagnostics, Journal Year: 2023, Volume and Issue: 13(11), P. 1841 - 1841

Published: May 24, 2023

Optical genome mapping (OGM) is a new genome-wide technology that can reveal both structural genomic variations (SVs) and copy number (CNVs) in single assay. OGM was initially employed to perform assembly research, but it now more widely used study chromosome aberrations genetic disorders human cancer. One of the most useful applications hematological malignancies, where chromosomal rearrangements are frequent conventional cytogenetic analysis alone insufficient, necessitating further confirmation using ancillary techniques such as fluorescence situ hybridization, microarrays, or multiple ligation-dependent probe amplification. The first studies tested efficiency sensitivity for SV CNV detection, comparing heterogeneous groups lymphoid myeloid sample data with those obtained standard diagnostic tests. Most work based on this innovative focused myelodysplastic syndromes (MDSs), acute leukemia (AML), lymphoblastic (ALL), whereas little attention paid chronic lymphocytic (CLL) myeloma (MM), none lymphomas. showed be considered highly reliable method, concordant able detect novel clinically significant SVs, thus allowing better patient classification, prognostic stratification, therapeutic choices malignancies.

Language: Английский

Citations

15
Genomic imbalances analysis provides new insight into prognostic factors in adult and pediatric T-ALL DOI
Estelle Balducci, Mathieu Simonin, Nicolas Duployez

et al.

Blood, Journal Year: 2024, Volume and Issue: 144(9), P. 988 - 1000

Published: Aug. 29, 2024

Language: Английский

Citations

5
Novel NUP98::ASH1L Gene Fusion in Acute Myeloid Leukemia Detected by Optical Genome Mapping DOI Open Access
Marco Tembrink, Wanda M. Gerding,

Stefan Wieczorek

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(11), P. 2942 - 2942

Published: May 27, 2023

Optical genome mapping (OGM) recently has demonstrated the potential to improve genetic diagnostics in acute myeloid leukemia (AML). In this study, OGM was utilized as a tool for detection of genome-wide structural variants and disease monitoring. A previously unrecognized NUP98::ASH1L fusion detected an adult patient with secondary AML. identified NUP98 Absent, Small, or Homeotic-Like Histone Lysine Methyltransferase (ASH1L) result complex rearrangement between chromosomes 1 11. pipeline measurement rare (Rare Variant Pipeline, Bionano Genomics, San Diego, CA, USA) used detection. As other fusions are relevant classification, demonstrates necessity methods such cytogenetic Furthermore, showed discordant variant allele frequencies at different time points over course treatment pressure, indicating clonal evolution. These results support be valuable primary AML well longitudinal testing monitoring deepening our understanding genetically heterogenous diseases.

Language: Английский

Citations

10
False positive NUP98 Fluorescence In Situ Hybridization Rearrangements in B-Acute Lymphoblastic Leukemia DOI Creative Commons

Marie-France Gagnon,

Sahil Tonk,

Benjamin Carcamo

et al.

Cancer Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
OMKar: optical map based automated karyotyping of genomes to identify constitutional abnormalities DOI Creative Commons
Siavash R. Dehkordi, Zhaoyang Jia,

Joey Estabrook

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

The whole genome karyotype refers to the sequence of large chromosomal segments that make up an individual's genotype. analysis, which includes descriptions aneuploidies and other rearrangements is crucial for understanding genetic risk factors, diagnosis, treatment decisions, counseling linked constitutional disorders. current karyotyping standard based on microscopic examination chromosomes, a complex process requires high expertise offers Mb scale resolution. Optical Genome Mapping (OGM) technology can identify DNA lesions in cost-effective manner. In this paper, we developed OMKar, method uses OGM data create virtual karyotype. OMKar processes Structural (SV) Copy Number (CN) Variants as inputs encodes them into compact breakpoint graph. It recomputes copy numbers using Integer Linear Programming maintain CN balance then identifies constrained Eulerian paths representing entire donor chromosomes. tests 38 simulations disorders, reconstructed with 88% precision 95% recall SV concordance Jaccard score concordance. We applied 50 prenatal, 41 postnatal, 63 parental samples from ten different sites. correct 144 out 154 samples, covering 25 aneuploidies, 32 balanced translocations, 72 82 unbalanced variations. Detected disorders included Cri-du-chat, Wolf-Hirschhorn, Prader-Willi deletions, Down, Turner syndromes. Importantly, it identified plausible mechanism five cases disorder were not detected by technologies. Together, these results demonstrate robustness OGM-based karyotyping. publicly available at https://github.com/siavashre/OMKar .

Language: Английский

Citations

0