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An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup [CITE-seq]

ABSTRACT: An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup [CITE-seq]

PROVIDER: PRJNA982124 | ENA |

REPOSITORIES: ENA

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An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup [CITE-seq]

Project description:T-cell acute lymphoblastic leukemia (T-ALL), a malignant neoplasm of immature T cells, is a particularly aggressive leukemia with diverse subtypes and limited therapeutic options. Recent studies showed that the responsiveness of drugs in preclinical models of T-ALL is linked to the specific biological characteristics exhibited by the T-ALL subtype. In order to comprehensively explore the underlying heterogeneity of T-ALL, we performed an integrative analysis of bone marrow biopsies from newly diagnosed T-ALL patients. Leveraging a combination of cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) along with T-cell receptor sequencing (TCR-seq), we obtained a comprehensive molecular characterization of T-ALL. Our analysis uncovered a distinct subset of inflammatory T-ALLs (iT-ALLs) resembling early T-cell precursor (ETP) leukemias, characterized by enriched expression of hematopoietic stem and progenitor signatures, inflammatory gene programs, and poor survival outcomes. Furthermore, our investigation revealed a significant association between the transcription factor interferon regulatory factor 5 (IRF5) activity and the iT-ALL subgroup. Utilizing an IRF5 scoring system, we demonstrated its potential as a robust biomarker for classifying T-ALL patients and predicting disease prognosis. Our work provides a framework for identifying high-risk T-ALL patients based on the IRF5 activity and a rational for considering the inflammatory state in tailoring therapeutic interventions.

2024-12-31 | GSE234610 | GEO

An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup

Project description:An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup

| PRJNA982126 | ENA

An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup [bulkRNA-Seq]

2024-12-31 | GSE234608 | GEO

An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup [bulkRNA-Seq]

Project description:An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup [bulkRNA-Seq]

| PRJNA982121 | ENA

IG-MYC rearrangement defines a high-risk subgroup of B-cell precursor acute lymphoblastic leukaemia

Project description:IG-MYC rearrangement defines a high-risk subgroup of B-cell precursor acute lymphoblastic leukaemia

| PRJNA728958 | ENA

An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-12-31 | GSE234612 | GEO

The Evolving Immune Microenvironment of Human B-cell Acute Lymphoblastic Leukemia [CITE-Seq]

Project description:The Evolving Immune Microenvironment of Human B-cell Acute Lymphoblastic Leukemia [CITE-Seq]

| PRJNA642147 | ENA

IG-MYC rearrangement defines a high-risk subgroup of B-cell precursor acute lymphoblastic leukaemia

Project description:We assessed the molecular relationship of IG-MYC rearranged ALL with other ALL subtypes and Burkitt’s lymphoma and describe the genetic and clinical outcomes of IG-MYC rearranged ALL

2022-05-31 | GSE174248 | GEO

Sonic Hedgehog subgroup medulloblastomas

Project description:Sonic Hedgehog subgroup medulloblastomas

| PRJNA384622 | ENA

Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia.

Project description:KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) represents the most refractory type of childhood leukemia. To uncover the molecular heterogeneity of this disease, we perform RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with KMT2A-rearranged leukemia. Our multi-omics clustering followed by single-sample and single-cell inference of hematopoietic differentiation establishes five robust integrative clusters (ICs) with different master transcription factors, fusion partners and corresponding stages of B-lymphopoietic and early hemato-endothelial development: IRX-type differentiated (IC1), IRX-type undifferentiated (IC2), HOXA-type MLLT1 (IC3), HOXA-type MLLT3 (IC4), and HOXA-type AFF1 (IC5). Importantly, our deep mutational analysis reveals that the number of RAS pathway mutations predicts prognosis and that the most refractory subgroup of IC2 possesses 100% frequency and the heaviest burden of RAS pathway mutations. Our findings highlight the previously under-appreciated intra- and inter-patient heterogeneity of KMT2A-rearranged infant ALL and provide a rationale for the future development of genomics-guided risk stratification and individualized therapy.

| S-EPMC9427775 | biostudies-literature

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