Dynamic changes of the sympathetic nervous system in the bone marrow in myeloid leukaemia.

Abstract

Chronic myeloid leukaemia (CML) is a hematologic malignancy originating from hematopoietic stem cells with the fusion oncogene BCR-ABL1 on the Philadelphia chromosome, which drives the abnormal proliferation of leukemic blast cells within the bone marrow microenvironment. While previous research has primarily focused on the hematopoietic compartment, the functional contribution of the bone marrow microenvironment to the CML pathology remains understudied. We investigated the changes in the peripheral nervous system in the bone marrow with myeloid leukaemia via immunofluorescence staining of tyrosine hydroxylase (TH) and calcitonin gene-related peptide (CGRP) antibodies in mouse with NUP98-HOXA9- and BCR-ABL1-expressing myeloid leukaemia. We found that the TH-positive fibres were significantly reduced, while no overt changes were observed in CGRP-positive nerves in the bone marrow. The reduction in TH-positive nerve cells was also evident in the spleen. Human patient gene expression data suggested that the levels of sympathetic nerve receptor expression change during the blastic transformation of human CML. Our findings indicate that the sympathetic nervous system regulates the pathogenesis of myeloid leukaemia and could play a crucial role in the disease progression of myeloid leukaemia.