Fig. 3: Targeting the IL-1β pathway overcomes ineffective erythropoiesis in lower-risk-MDS. | Nature Communications

Fig. 3: Targeting the IL-1β pathway overcomes ineffective erythropoiesis in lower-risk-MDS.

From: The IL-1β inhibitor canakinumab in previously treated lower-risk myelodysplastic syndromes: a phase 2 clinical trial

Fig. 3

A Schematic of hemoglobin and platelet levels in patient UPN-02 and the number of packed red blood cell (PRBC) units received before and after therapy. The black arrow indicates the response duration. C, cycle. Created in BioRender. Rodriguez-Sevilla, J.J., (2024) https://. BioRender.com/t63n194. B UMAP plot of scRNA-seq data from Lin-CD34+ cells from the BM of patient UPN-02 before (PRE; n = 1381) and after 2, 4, 5, 8, 11, and 14 cycles of canakinumab treatment (n = 5721). Different colors represent the sample (left) and cluster (right) identities. My, myeloid; Lymph, lymphoid; HSC, hematopoietic stem cell; Mk, megakaryocytic; Er, erythroid. C Cluster distribution of Lin-CD34+ cells from the BM before canakinumab treatment (PRE) and at the time of response (cycles 2, 4, 5, 8, and 11) or relapse (cycle 14), represented as the percentage of cells in each cluster. Black arrows indicate the Mk/Er clusters. RESP, response. For the Mk/Er clusters, comparing samples C2, C4, C5, C8, C11, and C14 to the PRE sample: P = 0.92, 0.00077, 4.57 × 10-6, 0.097, 1.06 × 10-45, and 0.0015, respectively; two-sided Chi-square test. D Pathway enrichment analysis of genes significantly (P ≤ 0.05) downregulated in HSCs after 2 cycles of canakinumab treatment compared with those before treatment. The top 10 Hallmark gene sets are shown. E UMAP plot of scRNA-seq data from BM MNCs isolated from patient UPN-02 before canakinumab treatment (PRE; n = 2980) and after 2, 4, 5, 8, 11, and 14 cycles of treatment (n = 27,913). Different colors represent the sample (left) and cluster (right) identities. F Pathway enrichment analysis of genes significantly (P ≤ 0.05) downregulated in monocytes after 2 cycles of canakinumab treatment compared with those before treatment. The top 10 Hallmark gene sets are shown. G Cluster distribution of BM MNCs before canakinumab treatment (PRE), at the time of response (cycles 2, 4, 5, 8, and 11) or relapse (cycle 14), represented as the percentage of cells in each cluster. For the memory-2 T cell cluster, comparing samples C2, C4, C5, C8, C11, and C14 to the PRE sample: P = 7.49 × 10-27, 1.50 × 10-7, 0.021, 1,22 × 10-20, 7.67 × 10-30, and 0.036, respectively; two-sided Chi-square test. HSPC, hematopoietic stem and progenitor cell; Mk, megakaryocytic; GMP, granulo-monocytic progenitor; Mono, monocytic; Er, erythroid; Prec, precursor; NK, natural killer; Lymph, lymphoid; PC, plasma cell; Baso, basophil; mem, memory; RESP, response. Source data are provided as a Source Data file.

Back to article page