Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia The heterogeneity and evolution of AML blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed whole-exome sequencing and single-cell RNA-seq to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases.

The single cell RNA data underpinned the tumor heterogeneity amongst patient blasts. The Dx-Re transcriptomes of high risk FLT3-ITD pairs formed a continuum from extensively changed in the absence of significantly mutational changes in AML-associated genes to rather similar Dx-Re pair of an intermediate risk FLT3-ITD. In one high risk FLT3-ITD pair, a pathway switched from an AP-1 regulated network in Dx to mTOR signaling in Re. The distinct AML1-ETO pairs comprise clusters that share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells probably evolved from the Dx LSC-like cells.

In summary, our study revealed a continuum from drastic transcriptional changes to extensive similarities between respective Dx-Re pairs that are poorly explained by the well-established model of clonal evolution. Our results suggest alternative and currently unappreciated and unexplored mechanisms leading to therapeutic resistance and AML recurrence.
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The categories of this paper are: cognition
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The categories of this paper are: molecular
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The categories of this paper are: neuroscience
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The categories of this paper are: pharmacology
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The categories of this paper are: physiology
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The categories of this paper are: developmental
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The categories of this paper are: animal
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The categories of this paper are: genomics
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The categories of this paper are: biochemistry
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The categories of this paper are: systems
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The categories of this paper are: plant
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The categories of this paper are: behavior
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The categories of this paper are: education
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The categories of this paper are: communication
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The categories of this paper are: bioengineering
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The categories of this paper are: zoology