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Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification [DAb-seq]

ABSTRACT: Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification [DAb-seq]

PROVIDER: PRJNA962722 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24331201_1.fastq.gz	Fastqsanger.gz
	SRR24331201_2.fastq.gz	Fastqsanger.gz
	SRR24331202_1.fastq.gz	Fastqsanger.gz
	SRR24331202_2.fastq.gz	Fastqsanger.gz
	SRR24331203_1.fastq.gz	Fastqsanger.gz

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Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification [DAb-seq]

Project description:Mixed phenotype acute leukemia (MPAL) also known as acute leukemia of ambiguous lineage (ALAL), is characterized by leukemic blasts with both lymphoid and myeloid cell surface markers. Here, we use SC multiomic profiling on newly diagnosed MPAL samples to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. This profiling allows us to definitively contradict the paradigm of MPAL as a disease on a continuum with myeloid and lymphoid lineage acute leukemias, and instead identifies MPAL as a distinct, stem-like disease that, unlike other leukemias, cannot be defined by genetics alone. We further describe a stem cell gene expression signature for MPAL that can predict patient survival. These results broaden our understanding of MPAL biology and suggest a path toward novel risk stratification for MPAL. Importantly, these findings have potential to direct treatment and, hopefully, ultimately improve the prognosis of this disease.

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Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification

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Project description:Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification [PIP-seq]

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Project description:Mixed phenotype acute leukemia (MPAL) is a leukemia whose biologic drivers are poorly understood, therapeutic strategy remains unclear, and prognosis is poor. We performed multiomic single cell (SC) profiling of 14 newly diagnosed adult MPAL patients to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. However, progressive acquisition of mutations is associated with increased expression of immunophenotypic markers of immaturity. Using SC transcriptional profiling, we find that MPAL blasts express a stem cell-like transcriptional profile distinct from other acute leukemias and indicative of high differentiation potential. Further, patients with the highest differentiation potential demonstrated inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in this cohort, is applicable to bulk RNA sequencing data and was predictive of survival in an independent patient cohort, suggesting utility for clinical risk stratification.

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