1003 – EIF4E DRIVES AML CELL COLONIZATION OF THE BONE MARROW NICHE: INSIGHTS FROM A 3D MESENCHYMAL SPHEROID CO-CULTURE MODEL

IF 2.7 4区医学 Q2 HEMATOLOGY

Experimental hematology Pub Date : 2026-10-01 Epub Date: 2026-10-23 DOI:10.1016/j.exphem.2026.105499

Monica Guzman

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Abstract

The crosstalk between acute myeloid leukemia (AML) cells and the bone marrow niche is crucial for disease progression. Modeling AML-niche interactions is key because these interactions support survival, chemotherapy resistance, and disease maintenance, and the niche serves as a specialized microenvironment for leukemia stem cells.

We have implemented a three-dimensional (3D) in vitro model that mimics the leukemic bone marrow niche, particularly the interaction between AML cells and mesenchymal stromal cells (MSCs). This model consists of a spheroid formed from bone marrow MSCs without synthetic scaffolds or exogenous materials. AML cells are cocultured with the spheroid to assess their colonization capacity.

Using this model, we identified a new role for eukaryotic translation initiation factor 4E (eIF4E) in adhesion and colonization, as demonstrated through genetic and pharmacologic depletion of eIF4E. These findings were also validated in vivo.

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1003 - eif4e驱动骨髓生态位的aml细胞定植：来自3d间充质球体共培养模型的见解

急性髓性白血病（AML）细胞与骨髓生态位之间的串扰对疾病进展至关重要。aml -生态位相互作用的建模是关键，因为这些相互作用支持生存、化疗耐药性和疾病维持，而生态位是白血病干细胞的专门微环境。我们已经实现了一个三维（3D）体外模型，模拟白血病骨髓生态位，特别是AML细胞和间充质基质细胞（MSCs）之间的相互作用。该模型由骨髓间充质干细胞形成的球体组成，没有合成支架或外源材料。AML细胞与球体共培养以评估其定植能力。利用这个模型，我们发现了真核翻译起始因子4E （eIF4E）在粘附和定植中的新作用，正如eIF4E的遗传和药理学消耗所证明的那样。这些发现在体内也得到了验证。急性髓性白血病（AML）细胞与骨髓生态位之间的串扰对疾病进展至关重要。aml -生态位相互作用的建模是关键，因为这些相互作用支持生存、化疗耐药性和疾病维持，而生态位是白血病干细胞的专门微环境。我们已经实现了一个三维（3D）体外模型，模拟白血病骨髓生态位，特别是AML细胞和间充质基质细胞（MSCs）之间的相互作用。该模型由骨髓间充质干细胞形成的球体组成，没有合成支架或外源材料。AML细胞与球体共培养以评估其定植能力。利用这个模型，我们发现了真核翻译起始因子4E （eIF4E）在粘附和定植中的新作用，正如eIF4E的遗传和药理学消耗所证明的那样。这些发现在体内也得到了验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental hematology 医学-血液学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

58 days

期刊介绍： Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.