| Autor: |
Dajeong Jeong, Amos C. Lee, Kyoungseob Shin, Jinhyun Kim, Myoung Hee Ham, Changhee Lee, Sumin Lee, Ahyoun Choi, Taehoon Ryu, Okju Kim, Yushin Jung, Sunghoon Kwon, Dong Soon Lee |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Reports: Methods, Vol 3, Iss 10, Pp 100617- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2667-2375 |
| DOI: |
10.1016/j.crmeth.2023.100617 |
| Popis: |
Summary: Co-occurrence of multiple myeloma and acute myelogenous leukemia is rare, with both malignancies often tracing back to multipotent hematopoietic stem cells. Cytogenetic techniques are the established baseline for diagnosis and characterization of complex hematological malignancies. In this study, we develop a workflow called Hema-seq to delineate clonal changes across various hematopoietic lineages through the integration of whole-genome sequencing, copy-number variations, cell morphology, and cytogenetic aberrations. In Hema-seq, cells are selected from Wright-stained slides and fluorescent probe-stained slides for sequencing. This technique therefore enables direct linking of whole-genome sequences to cytogenetic profiles. Through this method, we mapped sequential clonal alterations within the hematopoietic lineage, identifying critical shifts leading to myeloma and acute myeloid leukemia (AML) cell formations. By synthesizing data from each cell lineage, we provided insights into the hematopoietic tree’s clonal evolution. Overall, this study highlights Hema-seq’s capability in deciphering genomic heterogeneity in complex hematological malignancies, which can enable better diagnosis and treatment strategies. Motivation: Hematological malignancies, with their intricate molecular landscapes, present significant challenges in the diagnostic and therapeutic realms. The co-existence of neoplastic and normal cells within these malignancies further adds to this complexity. Traditional cytogenetic methods, while invaluable, cannot resolve the full spectrum of genomic aberrations, especially in rare simultaneous occurrences. We therefore sought to bring the greater degree of genomic resolution afforded by whole-genome sequencing to samples that have been processed and preserved through cytogenetic methods and to link sequencing profiles to selected cell populations for higher-resolution clonal reconstruction and analysis. Such an approach not only holds promise in unveiling the mysteries of clonal evolution but also in guiding tailored therapeutic strategies for enhanced patient outcomes. In short, our work with “Hema-seq” is driven by the motivation to bridge existing gaps and offer a panoramic view of the genomic intricacies within hematopoietic lineage cells. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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