Transcriptomics of acute myeloid leukaemia core bone marrow biopsies reveals distinct therapy response‐specific osteo‐mesenchymal profiles

Abstract

While the bone marrow (BM) microenvironment is significantly remodelled in acute myeloid leukaemia (AML), molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma. We assessed the effect of anthracycline-and cytarabine-based induction chemotherapy on both haematopoietic and non-haematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis. We compared matched human core BM biopsies at diagnosis and 2 weeks after cytarabine-and anthracycline-based induction therapy in responders (<5% blasts present after treatment) and non-responders (≥5% blasts present after treatment). Our data indicated enrichment in vimentin (VIM), platelet-derived growth factor receptor beta (PDGFRB) and Snail family transcriptional repressor 2 (SNAI2) transcripts in responders, consistent with the reactivation of the mesenchymal population in the BM | 741 TREABA et al.

The relevance of the hematopoietic niche for therapy resistance in acute myeloid leukemia

“…In transcriptome analyses of BM biopsies from patients undergoing cytarabine chemotherapy, upregulation of osteoblast maturation transcripts was found after treatment 41 . Notably, the enrichment of osteopontin, osteonectin and biglycan were especially seen in therapy nonresponders.…”

Treatment response in acute myeloid leukaemia—Clues in the biopsy core

“…To investigate CTX‐induces changes in BM of patients with AML, Treaba et al 8 analysed gene expression profiles of matched BM core biopsies at diagnosis and after ‘7 + 3’ cytarabine and anthracyclines regimen in 29 patients with AML. The team coupled bulk RNA sequencing and microarray expression profiles with histology, stratifying patients as CTX responders ( n = 15) and non‐responders ( n = 14).…”

“…9 Despite this progress, it is still challenging to find the best treatment option at diagnosis and relapse of each patient. Here, Treaba et al 8 reported the downregulation in specific gene expression signatures at diagnosis in patients who later failed to respond to the '7 + 3' CTX regimen. These gene signatures were associated with impaired erythropoiesis and given that most AML patients develop anaemia, this could indicate a more severe phenotype for these patients.…”