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Dynamic transcriptomic tracking directs the treatment for acute leukemia of ambiguous lineage

ABSTRACT: Dynamic transcriptomic tracking directs the treatment for acute leukemia of ambiguous lineage

PROVIDER: PRJNA495930 | ENA |

REPOSITORIES: ENA

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Dynamic transcriptomic tracking directs the treatment for acute leukemia of ambiguous lineage

Project description:Acute leukemia of ambiguous lineage (ALAL) is a rare subtype of acute leukemia characterized by the lack of straightforward myeloid or lymphoid lineage commitment. Currently, no treatment guidelines are commonly-accepted for ALAL. Herein, we have established an molecular-guided therapeutic approach to classify ALAL as either possessing an transciptional profile with a tendency towards acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). A three and a half years perspective study saw an ALAL patient failed to respond to the ALL-like treatment recommended in most retrospective studies. However, RNA-seq profiling of this ALAL, together with indepth comparative analysis with AML, ALL and healthy bone marrow samples, demonstrated that the ALAL was transcriptomically more similar to AML, and correspondingly a complete molecular remission (CMR) was achieved with AML-like treatment regimen. Moreover, tracking of transcriptomic profile changes at nine time points throughout the treatment successfully detected tumor relapse seven months earlier than conventional approaches. Under the guidance of this Dynamic Transcriptomic Tracking (DTT) approach, we present a further ALAL patient that reached CMR with an AML-like treatment regimen. DTT maybe beneficial in other leukemias that do not possess recommended treatment guidelines. We propose that DTT is condidered for perspective trials.

2023-12-23 | GSE121169 | GEO

MicroRNA expression profiling of leukemias of ambiguous lineage

Project description:Classifying leukemias of ambiguous lineage as either acute myeloid leukemia or acute lymphoid leukemia using microRNA expression profiling

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Lineage tracking reveals dynamic relationships of T cells in colorectal cancer

Project description:Lineage tracking reveals dynamic relationships of T cells in colorectal cancer

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Lineage tracking reveals dynamic relationships of T cells in colorectal cancer

Project description:T cells are central players in cancer immunotherapy1, yet some of their fundamental properties such as development and migration within tumours remain elusive. The enormous T cell receptor (TCR) repertoire, required for recognising foreign and self-antigens2,3, could serve as lineage tags to track these T cells in tumours4. Here, we obtained transcriptomes of 11,138 single T cells from 12 colorectal cancer (CRC) patients and developed STARTRAC (Single T-cell Analysis by Rna-seq and Tcr TRACking) indices to quantitatively analyse dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. While both CD8+ effector and ?exhausted? T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, the majority of tumour-infiltrating Tregs showed clonal exclusivity, whereas certain Treg clones were developmentally linked to multiple TH clones. Notably, we identified two IFNG+ TH1-like clusters in tumours, the GZMK+ TEM and CXCL13+ TH1-like clusters, which were associated with distinct IFN-?-regulating transcription factors, EOMES/RUNX3 and BHLHE40, respectively. Only BHLHE40+ CXCL13+ TH1-like cells were preferentially enriched in tumours of microsatellite-instable (MSI) patients, which might explain their favourable response rates to immune-checkpoint blockade. Furthermore, we found IGFLR1 to be highly expressed in both BHLHE40+CXCL13+ TH1-like and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provided a powerful avenue to comprehensively dissect the T cell properties in CRC, which could shed new insights into the dynamic relationships of T cells in other cancers.

2018-10-29 | GSE108989 | GEO

Ambiguous genetic codes

Project description:Crammed, ambiguous genetic codes

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Transcription profiling of human 239T cells shows SUMOylation of DRIL1 directs its transcriptional activity towards leukocyte lineage-specific genes

Project description:SUMOylation of DRIL1 directs its transcriptional activity towards leukocyte lineage-specific genes

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BCL11B enhancer hijacking defines a subtype of lineage ambiguous stem cell leukemia

Project description:BCL11B enhancer hijacking defines a subtype of lineage ambiguous stem cell leukemia

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BCL11B enhancer hijacking defines a subtype of lineage ambiguous stem cell leukemia [HiChIP]

Project description:BCL11B enhancer hijacking defines a subtype of lineage ambiguous stem cell leukemia [HiChIP]