Related Experiment Video
Updated: Sep 5, 2025

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
SEMA4D/PlexinB1 promotes AML progression via activation of PI3K/Akt signaling
Lu Liu1, Lin Yang1, Xiaojun Liu1
1Department of Hematology, Key Laboratory of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Background:
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. SEMA4D is a 150 kDa transmembrane protein that belongs to the IV class of the subfamily of semaphorin family. Previous studies have reported that SEMA4D is a multifunctional target in many solid tumors, involving multiple physiological systems, and there are emerging therapies to target these pathways. The role of SEMA4D in AML has not yet been explored.
Methods:
The SEMA4D expression prolile, clinical data and potential prognostic analysis were acquired via the cBioPortal and GEPIA databases. SEMA4D expression was measured using real-time quantitative PCR and western blot. Cell counting kit-8 (CCK8) and flow cytometry were used to evaluate the malignant biological characteristics.
Results:
We observed that SEMA4D was increased in AML patients and correlated with risk stratification and prognosis. Moreover, SEMA4D promotes the proliferation and inhibits apoptosis of AML cells by binding to its receptor, PlexinB1, and reduces the sensitivity of AML cells to daunorubicin. In addition, SEMA4D/PlexinB1 promotes the proliferation and survival of AML cells by activating the PI3K/Akt signaling pathway. VX15/2503, an anti-SEMA4D antibody, can inhibit the proliferation of AML cells in xenograft mouse models, thereby inhibiting the development of AML.
Conclusion:
SEMA4D will serve as a unique predictive biomarker and a possible therapeutic target in AML.
Insights
SEMA4D protein is elevated in acute myeloid leukemia (AML) and drives cancer growth by activating the PI3K/Akt pathway. Targeting SEMA4D with VX15/2503 antibody shows promise for AML treatment.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Acute myeloid leukemia (AML) is a prevalent adult leukemia.
- SEMA4D, a transmembrane protein, is implicated in various solid tumors.
- The function of SEMA4D in AML remains uninvestigated.
Purpose of the Study:
- To investigate the role of SEMA4D in AML.
- To explore SEMA4D as a potential therapeutic target and biomarker in AML.
Main Methods:
- Utilized cBioPortal and GEPIA for SEMA4D expression and clinical data analysis.
- Quantified SEMA4D expression via real-time quantitative PCR and western blot.
- Assessed AML cell proliferation and apoptosis using CCK8 and flow cytometry.
Main Results:
- SEMA4D expression is upregulated in AML patients, correlating with prognosis.
- SEMA4D promotes AML cell proliferation and survival by activating the PI3K/Akt pathway via PlexinB1.
- SEMA4D reduces AML cell sensitivity to daunorubicin.
- An anti-SEMA4D antibody (VX15/2503) inhibited AML growth in xenograft models.
Conclusions:
- SEMA4D is a potential predictive biomarker for AML.
- SEMA4D represents a promising therapeutic target for AML treatment.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The JAK-STAT Signaling Pathway
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
MAPK Signaling Cascades

