Bone marrow mesenchymal stromal cells in chronic myelomonocytic leukaemia: overactivated WNT/β‐catenin signalling by parallel RNA sequencing and dysfunctional phenotypes

Abstract

Sophisticated cross-talk between bone marrow mesenchymal stromal cells (BM MSCs) and haematopoietic/leukaemic stem cells in patients with myelodysplastic syndromes (MDS) and myeloid leukaemia have been emphasized in previous reports. However, mesenchymal elements in patients with chronic myelomonocytic leukaemia (CMML) were poorly investigated. By utilizing a parallel RNA-sequencing method, we investigated the transcriptional profile and functional defects of primary BM MSCs from patients with CMML for the first time. Within a 24-patient cohort, transcriptional and functional analysis reveals a prominent enrichment of WNT/b-catenin signalling and multiple biology processes. Deregulated expression of WNT/b-catnin factors CTNNB1, CMYC, LEF1, and FRZB is associated with impaired proliferation, senescence phenotype, and abnormal secretion in CMML MSCs. The impaired ability to support healthy CD34 + haematopoietic stem and progenitor cells (HSPCs) correlates with activation of WNT/b-catenin signalling in CMML MSCs. Furthermore, we observed an association between WNT/b-catenin factors and treatment response to hypomethylating agents (HMAs) in a cohort of patients with MDS/myeloproliferative neoplasms (MPNs). Taken together, our study provides evidence for transcriptional and functional abnormalities in CMML MSCs, and suggests potential prognostic value of evaluating WNT/b-catenin signalling in patients with CMML.

Mesenchymal stem cells reversibly de-differentiate myofibroblasts to fibroblast-like cells by inhibiting the TGF-β-SMAD2/3 pathway

“…Since MSC is a group of cellular properties with secretory functions and shares a common mesenchymal origin with FB and MFB, we next sought to investigate the potential assimilation effect on the co-cultured MFB. After directly comparing the transcriptomes of co-cultured MFB with our previously published data of normal MSCs (Xu et al 2021 ), our results ruled out the potential assimilation effect by confirming the lack of expression of MSC-specific transcripts in these co-cultured cells (Additional file 1 : Fig. S2).…”

ALL blasts drive primary mesenchymal stromal cells to increase asparagine availability during asparaginase treatment

“…Interestingly, although this hypothesis awaits experimental validation, epigenetic modulation of MSC gene expression has been repeatedly described in hematological malignancies. 47,48 …”

Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing Their Cardio-Protective Properties

“…This possibility is sustained by the change in gene expression profiling in EVs. Indeed, not only are EV-naive no more enriched in DUSP6 [30], but EV-RIPC rearrange their gene content and become enriched in some stress-and cell-cycle-related genes [53][54][55][56][57]. We can speculate that DUSP6 enrichment in the hearts treated with EV-RIPC may represent a challenge to counteract the increase in Erk-1/2 activation.…”