B-cell precursor acute lymphoblastic leukemia cells use tunneling nanotubes to orchestrate their microenvironment

Roel Polak, Bob de Rooij, Rob Pieters, Monique L den Boer

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

138 Citaten (Scopus)

Samenvatting

Acute lymphoblastic leukemia (ALL) cells reside in the bone marrow microenvironment which nurtures and protects cells from chemotherapeutic drugs. The disruption of cell-cell communication within the leukemic niche may offer an important new therapeutic strategy. Tunneling nanotubes (TNTs) have been described as a novel mode of intercellular communication, but their presence and importance in the leukemic niche are currently unknown. Here, we show for the first time that primary B-cell precursor ALL (BCP-ALL) cells use TNTs to signal to primary mesenchymal stromal cells (MSCs). This signaling results in secretion of prosurvival cytokines, such as interferon-γ-inducible protein 10/CXC chemokine ligand 10, interleukin 8, and monocyte chemotactic protein-1/CC chemokine ligand 2. A combination of TNT-disrupting conditions allows us to analyze the functional importance of TNTs in an ex vivo model. Our results indicate that TNT signaling is important for the viability of patient-derived B-cell precursor ALL cells and induces stroma-mediated prednisolone resistance. Disruption of TNTs significantly inhibits these leukemogenic processes and resensitizes B-cell precursor ALL cells to prednisolone. Our findings establish TNTs as a novel communication mechanism by which ALL cells modulate their bone marrow microenvironment. The identification of TNT signaling in ALL-MSC communication gives insight into the pathobiology of ALL and opens new avenues to develop more effective therapies that interfere with the leukemic niche.

Originele taal-2Engels
Pagina's (van-tot)2404-14
Aantal pagina's11
TijdschriftBlood
Volume126
Nummer van het tijdschrift21
DOI's
StatusGepubliceerd - 19 nov. 2015

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