Bone marrow endothelial cell-derived interleukin-4 contributes to thrombocytopenia in acute myeloid leukemia

Haematologica
Ai GaoTao Cheng

Abstract

Normal hematopoiesis can be disrupted by the leukemic bone marrow microenvironment, which leads to cytopenia-associated symptoms including anemia, hemorrhage and infection. Thrombocytopenia is a major and sometimes fatal complication in patients with acute leukemia. However, the mechanisms underlying defective thrombopoiesis in leukemia have not been fully elucidated. In the steady state, platelets are continuously produced by megakaryocytes. Using an MLL-AF9-induced acute myeloid leukemia mouse model, we demonstrated a preserved number and proportion of megakaryocyte-primed hematopoietic stem cell subsets, but weakened megakaryocytic differentiation via both canonical and non-canonical routes. This primarily accounted for the dramatic reduction of megakaryocytic progenitors observed in acute myeloid leukemia bone marrow and a severe disruption of the maturation of megakaryocytes. Additionally, we discovered overproduction of interleukin-4 from bone marrow endothelial cells in acute myeloid leukemia and observed inhibitory effects of interleukin-4 throughout the process of megakaryopoiesis in vivo Furthermore, we observed that inhibition of interleukin-4 in combination with induction chemotherapy not only promoted recovery of p...Continue Reading

Citations

Jan 28, 2020·Blood Advances·Haydar ÇelikChristopher S Hourigan
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Yan ManYajie Wang

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Datasets Mentioned

BETA
GSE112942

Methods Mentioned

BETA
xenograft
flow cytometry
enzyme-linked immunosorbent assays
enzyme-linked immunosorbent assay

Software Mentioned

Volocity
SPSS Statistics
GraphPad Prism

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