The vascular bone marrow niche influences outcome in chronic myeloid leukemia via the E-selectin - SCL/TAL1 - CD44 axis

Abstract

The vascular bone marrow niche influences outcome in chronic myeloid leukemia via the E-selectin-SCL/TAL1-CD44 axis

Defining niche interactions to target chronic myeloid leukemia stem cells

“…19 The BM microenvironment is a developing research focus which is showing great importance in disease pathophysiology. Advances in technology, such as the time-lapse intra-vital imaging used in the study by Godavarthy et al, 1 are enabling a greater understanding of the interactions and mechanisms involved in cellular microenvironments This type of pioneering microscopy allows us to see interactions between leukemic cells and the niche, and is providing powerful data, as exemplified by this study as well as many others. 13 Enriching these data, single-cell RNA-sequencing allows for the analysis of the different cell types within the niche, evaluation of their transcriptional regulation and a view of how they may contribute to disease progression, providing important information which may have been masked using bulk sequencing approaches.…”

“…n this issue of Haematologica, Godavarthy et al 1 describe how the expression of CD44 on the surface of leukemic stem cells (LSC) and E-selectin on bone marrow (BM) endothelium are essential for the engraftment of LSC within the BM niche. They show how this interaction can provide the LSC with protection from imatinib treatment.…”

“…Godavarthy et al 1 demonstrate a novel reciprocal link between the external cues from the BM microenvironment and BCR-ABL-specific LSC-intrinsic pathways. They show how this leads to modulation of the expression of LSC adhesion molecules and alters interactions with the vascular niche.…”

“…They further showed that dislocation of BCR-ABL1 + cells from the niche, via inhibition of E-selectin binding, increased BCR-ABL + cell cycle progression and increased responsiveness to imatinib therapy. 1 Inhibition of E-selectin has been shown to have therapeutic utility in other cancer types, such as acute myeloid leukemia and solid tumors in which it is thought to have a role in metastasis. 15 In acute myeloid leukemia, the leukemic blast cells bind to E-selectin on the endothelium and this activates leukemic pathways that contribute to chemotherapy resistance.…”

CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity

“…reported by (33)(34)(35)(36)(37)(38) and multiple myeloma (n = 1)) were pretreated with/without HA and then settled on immobilized VCAM-1, followed by fixation and staining with α CD49d (red) and α CD34…”