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Biomedical subjects

Nan Yang

Publications and source records attributed to Nan Yang.

2 recordsLinked to original sources

Day + 30 detection of minimal residual FLT3-ITD by high-sensitivity PCR-NGS predicts relapse risk and guides post-transplant maintenance in AML.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes in patients with acute myeloid leukemia (AML) harboring FLT3-internal tandem duplication (FLT3-ITD) mutations. However, relapse still occurs in 15-35% of these patients after transplantation. Therefore, early and highly sensitive detection methods are required to identify patients at risk of relapse and enable timely post-transplant intervention. METHODS: In this NICHE cohort study, a total of 136 patients were included, then we evaluated whether high-sensitivity polymerase chain reaction (PCR)-next-generation sequencing (NGS) for FLT3-ITD (limit of detection: 5 × 10-6) on day + 30 post-HSCT could identify patients at a high risk of relapse and inform decisions regarding maintenance therapy. RESULTS: Among the 136 patients, 37 patients (27.2%) had detectable FLT3-ITD clones on day + 30. These patients exhibited a significantly higher cumulative incidence of post-HSCT multiparameter flow cytometry (MFC)-measurable residual disease (MRD) relapse (40.3% vs. 18.8%, p = 0.001). Notably, FLT3-ITD-positive patients who received FLT3 inhibitor maintenance therapy had no relapses, while 6 out of the 13 patients who did not receive maintenance therapy relapsed. Conversely, FLT3-ITD-negative patients without high-risk factors (2022 European LeukemiaNet adverse-risk group, relapsed/refractory AML, MFC-MRD positivity pre-HSCT) showed limited benefit from maintenance therapy (MFC-MRD-free survival: hazard ratio (HR) = 0.25 (0.03-2.11), p = 0.204; OS: HR = 0.20 (0.02-1.70), p = 0.142). CONCLUSIONS: This is the first study to demonstrate that detection of minimal FLT3-ITD clones at the fixed time point of day + 30 post-HSCT can reliably stratify relapse risk in AML patients and provide a rationale for individualized post-transplant maintenance therapy.

Humans

Deciphering the Protein Phosphorylation Dynamics Triggered by Seconds of Force Stimulation.

Plants perceive mechanical forces through phosphosignaling networks, but their relationship with gravity signaling remains elusive. To dissect gravity force signaling components, we performed SILIA-based phosphoproteomics on Arabidopsis aerial organs subjected to 20-s inversion or 30-s gravistimulation, identifying 2,733 and 2,878 phosphoproteins, respectively. Quantitative analysis revealed 34 significantly regulated phosphoproteins specific to inversion and 52 specific to gravistimulation. Inversion-specific phosphoproteins, associated with the initial calcium code, likely mediate calcium signals through EF-hand proteins, CPK1, and calmodulin-interacting proteins, potentially intersecting with receptor-like kinase-initiated MAPK cascades via RAF15 and MKK1/2 to induce gravitropic responses. Gravistimulation-specific phosphoproteins, linked to the secondary calcium code, function in calcium signaling/homeostasis (ACA8, ZAC, IQD2, ANNAT1), membrane vesicle trafficking (ABCG36, ARF-GAP8), and lipid signaling (PIP5K8/9), supporting auxin transport and stress signal transduction. Immunoblot validation confirmed treatment-associated phosphosites pS108-PATL3 and pS107-TREPH2, along with inversion-specific pS1145-ATEH2, exhibiting stem-specific phosphorylation enhancement and force-discriminatory responses. Functional analysis identified the integrin-like protein GREPH1 as a key gravitropism regulator, with greph1 mutants displaying reduced inflorescence stem gravicurvature. Notably, hyperphosphorylation of pS107-TREPH2 and pS1145-ATEH2 peaked at 20 to 50 s in greph1 mutants but persisted from 20 s to 2 h in WT plants. These findings establish a stem-enriched phosphorylation code for gravity force discrimination, with GREPH1 modulating spatiotemporal phosphoprotein dynamics and shoot gravicurvature, potentially functioning as a receptor reminiscent of sedimenting plastids.

Arabidopsis