Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Combined transcriptomic and proteomic analyses identified MMP14 as a key molecule in AMLMSC supporting leukemia cell growth. A , B . Analysis of apoptosis in primary leukemia cells after 48 h of co-culture with five cases each of AML-MSC and HD-MSC, using the Annexin V APC Apoptosis Detection Kit ( n = 5). Alone, leukemia cells cultured alone; Co, leukemia cells cocultured with MSCs. C , D . Flow BrdU assay for assessing the proliferation of primary leukemia cells after 48 h of co-culture with 5 AMLMSC and 5 HDMSC cases( n = 5). E . Volcano plots displaying the expression of differentially expressed genes between five AML-MSC and five HD-MSC samples, with purple representing upregulation and blue representing downregulation( n = 5). F . Enrichment analysis of differentially expressed genes. G . Proteomic analysis of supernatants from 4 AML-MSC and 4 HD-MSC samples, including a heat map of differentially expressed proteins( n = 4). H . Intersection analysis of differentially expressed genes identified in transcriptomic and proteomic analyses. I . Kaplan-Meier survival analysis of OHSU-AML dataset revealed that high expression of MMP14 is associated with poorer overall survival. J . PCR detection of MMP14 expression in AMLMSC ( n = 12) compared to HDMSC ( n = 6). K . Co-immunohistochemical staining of MMP14 (red) and CD271 (green) in AML and healthy control bone marrow samples. Scale bar = 20 μm ( n = 5)

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Co-Culture Assay, Cell Culture, BrdU Staining, Expressing, Immunohistochemical staining, Staining, Control

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Effects of MMP14 on MSC proliferation and cytokine secretion. A , B . Knockdown efficiency of MMP14 in MSCs verified by Western blot and RT-qPCR. C , D . Representative plots of CFU-F in the MMP14 knockdown and control groups. Quantification of CFU-F colonies in MSCs. E , F . BrdU assay showing cell proliferation rates in the MMP14 knockdown and control groups. G , H . Cell cycle analysis of the MMP14 knockdown and control groups. I - K . After co-culturing Kasumi-1 and Molm-13 cells with MSCs from the knockdown and control groups for 48 h, flow sorting was performed on the MSCs followed by PCR analysis of TGF-β1, CXCL12, CXCL10, OPN, and COX-2 gene expression levels

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Knockdown, Western Blot, Quantitative RT-PCR, Control, BrdU Staining, Cell Cycle Assay, Gene Expression

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Knockdown of MSC-derived MMP14 significantly inhibits AML progression in vitro. A - C . Flow cytometry analysis of apoptosis rates in Kasumi-1 and Molm-13 cells co-cultured with the knockdown and control groups for 48 h. D - F . Flow cytometry PI analysis of cell cycle changes in Kasumi-1 and Molm-13 cells co-cultured with the knockdown and control groups for 48 h. G - I . Flow cytometry BrdU analysis of cell proliferation rates in Kasumi-1 and Molm-13 cells co-cultured with the knockdown and control groups for 48 h

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Knockdown, Derivative Assay, In Vitro, Flow Cytometry, Cell Culture, Control

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Effect of MMP14 deletion in MSCs on disease progression and leukemic stem cells in MLL-AF9 leukemic mice. ( A ) The experimental layout involved transplanting MLL-AF9 cells via the tail vein and MSCs from MMP14 knockdown and control groups via intra-femoral injection into mice. AML progression was monitored by flow cytometric analysis. ( B ) Survival rates of mice in MMP14 knockdown and control groups after cell transplantation ( n = 7). ( C ) Live imaging was performed on days 14, 21, and 28 post-transplant to monitor disease progression and burden( n = 5). D , E . Flow cytometry plots of BM LSCs and statistical analysis of the proportion of LSC in whole BM ( n = 4). F . Statistical analysis of the proportion of leukemia cells in mice of both groups ( n = 4). G . Bone marrow cell count statistics in both groups of mice ( n = 4). H , I . Representative flow cytometry plots of LSC apoptosis and statistical analysis of the apoptosis rate of LSCs ( n = 4). J , K . Representative flow cytometry plots of the LSC cell cycle and statistical analysis of the percentage of apoptosis in LSCs ( n = 4)

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Knockdown, Control, Injection, Transplantation Assay, Imaging, Flow Cytometry, Cell Counting

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: MMP14 exerts its functions by activating the JAK-STAT pathway in AML cells through the secretion of PGE2. ( A ) Transcriptome analysis of Kasumi-1 cells co-cultured with MSCs from the MMP14 knockdown and control groups after 48 h. Volcano plots are shown. ( B ) Heat map of differentially expressed genes. ( C ) Enrichment analysis of differentially expressed genes. ( D ) GSEA analysis showing that MMP14 knockdown in MSCs is associated with inhibition of the JAK-STAT pathway. ( E ) Western blot analysis of STAT3, P-STAT3, STAT5, and P-STAT5 protein levels in Kasumi-1 and Molm-13 cells co-cultured with MSCs from the MMP14 knockdown and control groups. ( F ) ELISA assay of PGE2 levels in the supernatant of MSCs from the MMP14 knockdown and control groups. ( G ) ELISA assay of PGE2 levels in the serum of mice from the MMP14 knockdown group and the control group. H-J. Proliferation of Kasumi-1 and Molm-13 cells in the presence or absence of PGE2 (1 μm) in the co-culture system of the knockdown and control groups

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Cell Culture, Knockdown, Control, Inhibition, Western Blot, Enzyme-linked Immunosorbent Assay, Co-Culture Assay

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: MMP14 confers chemoresistance to Ara-C. A . Overview of the experimental design, dividing mice into four groups based on the presence or absence of the inhibitor (NSC-405020) and cytarabine. B . Survival statistics of mice ( n = 7). C - E . Representative FACS analysis and statistical proportions of leukemia cells in the four groups of mice ( n = 4). F . Representative images of Wright-Giemsa staining of bone marrow cells and hematoxylin-eosin staining of spleens. G . Representative images of mouse spleens. H - J . Immunohistochemical staining of P-STAT3 and P-STAT5 in mouse bone marrow and quantification of the staining. Scale bar, 50 μm

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Staining, Immunohistochemical staining

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Inhibition of MMP14 suppressed AML patient blasts. A - C . Flow cytometry analysis of apoptosis rates in primary leukemia cells co-cultured with the knockdown and control groups for 48 h. Alone, leukemia cells cultured alone; Co, leukemia cells cocultured with MSCs. D , E . Viable cells were counted using trypan blue staining and assessed with a hemocytometer after 48 h of co-culturing. F . Schematic of the PDX model construction process. Primary human leukemia cells were isolated from high-leukemia AML patients using leukapheresis and PBMC separation. These cells were then injected into NSG mice via the tail vein. Four weeks later, one mouse per week was randomly sacrificed, and the proportion of leukemia cells in the BM was analyzed by flow cytometry. Drug treatment commenced when the leukemia cell proportion reached ≥ 20%. Following successful PDX model construction, mice were randomly allocated to four treatment groups: DMSO-treated control (Ctrl), MMP14 inhibitor (inhibitor), cytarabine (Ara-C), and a combination of MMP14 inhibitor and cytarabine (inhibitor + Ara-C). G . Survival statistics for the mice were compiled ( n = 6). H-J. Flow cytometric representative plots and statistical analysis detailing the proportion and absolute numbers of human CD45 + cells in the four mouse groups ( n = 5)

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Inhibition, Flow Cytometry, Cell Culture, Knockdown, Control, Staining, Isolation, Injection

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Mechanism of action of MSC-derived MMP14 in promoting AML progression. The model illustrates how MSC-derived MMP14 promotes AML cell growth and chemotherapy resistance through the secretion of PGE2, activating the JAK-STAT pathway, leading to AML progression. Additionally, MSC-derived MMP14 enhances MSC proliferation and self-renewal, while also inducing cytokine alterations

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Derivative Assay