Evidence map›Paper›PMID 41954878›Full record

ArticleGenes & genomics2026

SEMA4A promotes acute myeloid leukemia progression through inhibiting apoptosis.

Xinyu Li, Binyu Yao, Meiling Sun, Wangshi Li, Xingzhi Lv, Keyang Luo, Yue Wu, Ruolin Xiu, Yuzhu Ma, Fukai Liu and 4 more

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Article in Genes & genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Xinyu Li *Department of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Binyu Yao *Department of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Meiling SunDepartment of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Wangshi LiDepartment of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Xingzhi LvDepartment of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Keyang LuoDepartment of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Yue WuDepartment of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Ruolin XiuDepartment of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Yuzhu MaDepartment of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Fukai LiuAnimal Laboratory Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Yanhong ZhaoDepartment of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Shengjin FanDepartment of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
Linqing TangDepartment of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China. tanglinqing@hrbmu.edu.cn.
Huitao FanDepartment of Critical Care Medicine, Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China. huitaofan@hrbmu.edu.cn.ORCID http://orcid.org/0000-0001-8250-3696

Funding

High-Level Overseas Talent Recruitment and Support Program High-Level Overseas Talent Recruitment and Support ProgramKey Joint Project of Heilongjiang Provincial Natural Science Foundation of China ZL2024H016Research Operating Project of Heilongjiang Provincial Scientific Research Institutes Research Operating Project of Heilongjiang Provincial Scientific Research Institutesthe National Natural Science Foundation of China 82370156the startup funding of the First Affiliated Hospital of Harbin Medical University RC-GCC2021-001
6 · The paper itself

Abstract

backgroundAcute myeloid leukemia (AML) is a highly aggressive hematologic malignancy. Currently, targeted therapy represents a transformative approach in the treatment of this disease. Semaphorin 4A (SEMA4A) is a member of the semaphorin family of soluble and transmembrane proteins. Recent evidence further identifies it as a novel immunotherapeutic target in myeloma. However, its functional significance in AML remains elusive.

objectiveThis study investigates the expression of SEMA4A in AML and its potential pathogenic mechanisms.

methodsInitially, we performed database analysis to evaluate SEMA4A expression. To investigate its biological function, SEMA4A was silenced in AML cells via shRNA, and RT-qPCR and Western blot confirmed its knockdown. Apoptosis, differentiation, and cell cycle were assessed by flow cytometry. Combination drug assays further validated a role of SEMA4A in mediating chemoresistance. In vivo, the growth of leukemic cells and mouse survival were assessed through xenotransplantation models. RNA sequencing ultimately uncovered the underlying mechanisms driving these phenotypes.

resultsSEMA4A deletion in AML cells reduced proliferative and clonogenic capacity. We observed increased apoptosis, enhanced differentiation, and G0/G1 cell cycle arrest. Furthermore, SEMA4A deletion in vivo prolonged survival. Mechanistically, RNA-seq analysis revealed significant activation of apoptotic pathways following SEMA4A loss. Notably, SEMA4A knockdown led to a marked reduction in BCL-2 expression and upregulation of the BCL-2 family members BMF and BBC3. SEMA4A deficiency also sensitized AML cells to chemotherapy, lowering effective drug doses and inducing extensive apoptosis.

conclusionOur findings revealed the oncogenic role for SEMA4A, suggesting it represents a promising therapeutic target in AML patients.

Indexed as

ApoptosisLeukemia, Myeloid, AcuteSemaphorinsAnimalsCell Line, TumorCell ProliferationDisease ProgressionHumansMiceSEMA4A protein, humanSemaphorinsAcute myeloid leukemiaApoptosisBCL-2SEMA4ATherapeutic target

Identifiers

PMID41954878

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.