About TACH

  ABOUT

      Extending our efforts in targeted differentiation therapies in cancer, we have dissected the cellular heterogeneity of acute promyelocytic leukemia (APL) and its potential impact on all-trans retinoic acid (ATRA) therapy in vivo.


      We have employed the scRNA-seq technology to generate a single-cell transcriptome resource on the malignant APL blasts from 16 newly diagnosed APL patients, followed by a series of data analyses to gain new insights into APL cellular heterogeneity and its association with genomic and clinical properties of APL patients

      In summary, our resource and findings are significant with fourfold, summarized below:
    • Firstly, our resource allows us to characterize the intratumoral heterogeneity with multiple branches, including a small subpopulation of APL stem-like cells. The trajectory analysis provides evidence supporting the importance of these APL stem-like cells in establishing cellular differentiation hierarchy.
    • Secondly, we have showed that the stemness characteristics of APL stem-like cells are determined by PML/RARα and enhanced by FLT3-ITD.
    • Thirdly, the deconvolution analysis on a large cohort of 323 APL patients has further revealed that higher APL stem-like cell proportions are significantly associated with elevated white blood cells (WBC) levels and the FLT3-ITD event. We have also constructed an APL-specific stemness score that could effectively evaluate prognosis, especially early death in APL.
    • Finally, we have investigated the in vivo effects of ATRA on APL cellular hierarchies and found that ATRA could directly target APL primitive blasts, inducing their differentiation and maturation.
    • Source Data are provided for all data presented in Figures of the manuscript (to be published).

  PUBLICATIONS

    A PML/RARα direct target atlas redefines transcriptional deregulation in acute promyelocytic leukemia

    Blood 2021

    DOI: 10.1182/blood.2020005698

    Acute Promyelocytic Leukemia: A Paradigm for Oncoprotein-Targeted Cure

    Cancer Cell 2017

    DOI: 10.1016/j.ccell.2017.10.002

    PML/RARa Targets Promoter Regions Containing PU.1 Consensus and RARE Half Sites in Acute Promyelocytic Leukemia

    Cancer Cell 2010

    DOI: 10.1016/j.ccr.2009.12.045

    Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy

    Philosophical Transactions of the Royal Society B 2007

    DOI: 10.1098/rstb.2007.2026

    Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia

    Proc Natl Acad Sci U S A 2005

    DOI: 10.1073/pnas.0502825102

    All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia

    Proc Natl Acad Sci U S A 2004

    DOI: 10.1073/pnas.0400053101