What question did this study set out to answer?

To investigate whether the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib blocks SDF1/CXCR4-mediated migration and downstream intracellular signaling pathways in acute myeloid leukemia (AML).

September 16, 2014OncotargetOpen Access

Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML

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Authors

LZLyubov ZaitsevaUniversity of East Anglia MMMegan Y. MurrayUniversity of East Anglia MSManar ShafatUniversity College London

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Implication

In vitro study demonstrates ibrutinib blocks SDF1/CXCR4-driven migration and signaling in primary AML blasts, suggesting a potential role in clinical leukocytosis.

Key Points

To investigate whether the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib blocks SDF1/CXCR4-mediated migration and downstream intracellular signaling pathways in acute myeloid leukemia (AML).
Treated primary human AML blasts with clinically relevant concentrations of ibrutinib in vitro.
Assessed SDF1/CXCR4-directed leukemic blast migration and evaluated downstream BTK phosphorylation, AKT activation, and MAPK signaling cascades.
Ibrutinib significantly inhibited SDF1/CXCR4-mediated migration of primary human AML blasts at concentrations achievable in vivo.
Stimulation with SDF-1 induced BTK phosphorylation and downstream MAPK signaling in AML blasts, both of which were blocked by ibrutinib alongside SDF1-induced AKT activation.
Findings suggest that BTK inhibition may mobilize AML blasts out of protective bone marrow niches, potentially causing a transient rise in peripheral blast counts similar to effects observed in chronic lymphocytic leukemia.

Cite This Study

Zaitseva et al. (2014) studied this question.

synapsesocial.com/papers/6a70297ff44fa9f079ddb885 https://doi.org/10.18632/oncotarget.2479

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Implication

In vitro study demonstrates ibrutinib blocks SDF1/CXCR4-driven migration and signaling in primary AML blasts, suggesting a potential role in clinical leukocytosis.

Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML

Discussion

Member takes

Implication

Key Points

Cite This Study

Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML

Discussion

Member takes

Implication

Key Points

Cite This Study

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