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Updated: Jul 27, 2025

Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
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Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk

Cheryl A C Peretz1,2, Vanessa E Kennedy3, Anushka Walia3

  • 1Divison of Hematology and Oncology, Department of Pediatrics, USA.

Biorxiv : the Preprint Server for Biology
|June 9, 2023
PubMed

Insights

Mixed phenotype acute leukemia (MPAL) is poorly understood. Single cell profiling reveals MPAL blasts have a stem cell-like profile linked to poorer survival, suggesting a new risk stratification tool.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Mixed phenotype acute leukemia (MPAL) presents diagnostic and therapeutic challenges due to poorly understood biologic drivers and poor prognosis.
  • Current understanding of MPAL's genetic and transcriptional landscape is limited, hindering effective treatment strategies.

Approach:

  • Multiomic single-cell (SC) profiling was employed on 14 newly diagnosed adult MPAL patients.
  • Analysis focused on characterizing the immunophenotypic, genetic, and transcriptional features of MPAL at a single-cell level.
  • A gene set score (MPAL95) was developed and validated for survival prediction in an independent cohort.

Key Points:

  • Neither genetic profiles nor transcriptomes reliably correlated with specific MPAL immunophenotypes.
  • Progressive acquisition of mutations correlated with increased expression of immature cell markers.
  • MPAL blasts exhibit a distinct stem cell-like transcriptional profile, suggesting high differentiation potential.
  • Higher differentiation potential in MPAL patients was associated with inferior survival.

Conclusions:

  • MPAL biology is complex, with a stem cell-like transcriptional profile contributing to its aggressive nature.
  • The MPAL95 gene set score shows promise as a tool for clinical risk stratification in MPAL patients.
  • Further research into MPAL's unique biology may reveal novel therapeutic targets.

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