The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/FUS::ERG.

Acute myeloid leukemia (AML) with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis. However, its clinical and molecular features remain poorly defined. We determined the clinicopathological, genomic, and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center. Thirty-six AML patients harboring FUS::ERG were identified, with an incidence rate of 0.3%. These patients were characterized by high lactate dehydrogenase levels (median: 838.5 U/L), elevated bone marrow blast counts (median: 71.5%), and a CD56-positive immunophenotype (94.3%). Notably, we found that RTK-RAS GTPase (RAS) pathway genes, including NRAS (33%) and PTPN11 (24%), were frequently mutated in this subtype. Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), and RAS signaling pathways and upregulation of BCL2, the target of venetoclax, in FUS::ERG AML compared to RUNX1::RUNX1T1 AML, a more common AML subtype with good prognosis. The median event-free survival in patients with FUS::ERG AML was 11.9 (95% confidence interval [CI]: 9.0-not available [NA]) months and the median overall survival was 18.2 (95% CI: 12.4-NA) months. Allogeneic hematopoietic stem cell transplantation failed to improve outcomes. Overall, the high incidence of RTK-RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.

Correction to "Diterpenoid Tanshinones Can Inhibit Lung Cancer Progression by Improving the Tumor Microenvironment and Downregulation of NF-κB Expression".

[This corrects the article DOI: 10.1021/acsomega.3c09667.].

Nano-formulated delivery of active ingredients from traditional Chinese herbal medicines for cancer immunotherapy.

Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.

Diterpenoid Tanshinones Can Inhibit Lung Cancer Progression by Improving the Tumor Microenvironment and Downregulation of NF-κB Expression.

Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.

Beta-elemene: A phytochemical with promise as a drug candidate for tumor therapy and adjuvant tumor therapy.

BACKGROUND: ß-Elemene (IUPAC name: (1 S,2 S,4 R)-1-ethenyl-1-methyl-2,4-bis(prop-1-en-2-yl) cyclohexane), is a natural compound found in turmeric root. Studies have demonstrated its diverse biological functions, including its anti-tumor properties, which have been extensively investigated. However, these have not yet been reviewed. The aim of this review was to provide a comprehensive summary of ß-elemene research, with respect to disease treatment. METHODS: ß-Elemene-related articles were found in PubMed, ScienceDirect, and Google Scholar databases to systematically summarize its structure, pharmacokinetics, metabolism, and pharmacological activity. We also searched the Traditional Chinese Medicine System Pharmacology database for therapeutic targets of ß-elemene. We further combined these targets with the relevant literature for KEGG and GO analyses. RESULTS: Studies on the molecular mechanisms underlying ß-elemene activity indicate that it regulates multiple pathways, including STAT3, MAPKs, Cyclin-dependent kinase 1/cyclin B, Notch, PI3K/AKT, reactive oxygen species, METTL3, PTEN, p53, FAK, MMP, TGF-ß/Smad signaling. Through these molecular pathways, ß-elemene has been implicated in tumor cell proliferation, apoptosis, migration, and invasion and improving the immune microenvironment. Additionally, ß-elemene increases chemotherapeutic drug sensitivity and reverses resistance by inhibiting DNA damage repair and regulating pathways including CTR1, pak1, ERK1/2, ABC transporter protein, Prx-1 and ERCC-1. Nonetheless, owing to its lipophilicity and low bioavailability, additional structural modifications could improve the efficacy of this drug. CONCLUSION: ß-Elemene exhibits low toxicity with good safety, inhibiting various tumor types via diverse mechanisms in vivo and in vitro. When combined with chemotherapeutic drugs, it enhances efficacy, reduces toxicity, and improves tumor killing. Thus, ß-elemene has vast potential for research and development.

Diterpenoid tanshinones inhibit gastric cancer angiogenesis through the PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge is a kind of Chinese herbal medicine known for activating blood circulation and removing blood stasis, with the effect of cooling blood and eliminating carbuncles, and has been proven to have the effect of treating tumors. However, the inhibitory effect of Salvia miltiorrhiza Bunge extracts (Diterpenoid tanshinones) on tumors by inhibiting angiogenesis has not been studied in detail. AIM OF THE STUDY: This study aimed to investigate the anti-gastric cancer effect of diterpenoid tanshinones (DT) on angiogenesis, including the therapeutic effects and pathways. MATERIALS AND METHODS: This experiment utilized network pharmacology was used to identify relevant targets and pathways of Salvia miltiorrhiza Bunge-related components in the treatment of gastric cancer. The effects of DT on the proliferation and migration of human gastric cancer cell line SGC-7901 and human umbilical vein endothelial cell line HUVECs were evaluated, and changes in the expression of angiogenesis-related factors were measured. In vivo, experiments were conducted on nude mice to determine tumor activity, size, immunohistochemistry, and related proteins. RESULTS: The findings showed that DT could inhibit the development of gastric cancer by suppressing the proliferation of gastric cancer cells, inducing apoptosis, and inhibiting invasion and metastasis. In addition, the content of angiogenesis-related factors and proteins was significantly altered in DT-affected cells and animals. CONCLUSIONS: Results suggest that DT has potential as a therapeutic agent for the treatment of gastric cancer, as it can inhibit tumor growth and angiogenesis. It was also found that DT may affect the expression of the angiogenic factor VEGF through the PI3K/Akt/mTOR pathway, leading to the regulation of tumor angiogenesis. This study provides a new approach to the development of anti-tumor agents and has significant theoretical and clinical implications for the treatment of gastric cancer.

Regulator of G protein signaling 1 is a potential target in gastric cancer and impacts tumor-associated macrophages.

Regulator of G protein signaling 1 (RGS1) is closely associated with the tumor immune microenvironment and is highly expressed in various tumors and immune cells. The specific effects of RGS1 in the dynamic progression from chronic gastritis to gastric cancer have not been reported, and the role of tumor-associated macrophages (TAMs) is also unclear. In the present study, RGS1 was identified as an upregulated gene in different pathological stages ranging from chronic gastritis to gastric cancer by using Gene Expression Omnibus (GEO) screening together with pancancer analysis of The Cancer Genome Atlas and clinical prognostic analysis. The results indicated that RGS1 is highly expressed in gastric cancer and has potential prognostic value. We confirmed through in vivo experiments that RGS1 inhibited the proliferation of gastric cancer cells and promoted apoptosis, which was further corroborated by in vitro experiments. Additionally, RGS1 influenced cell migration and invasion. In our subsequent investigation of RGS1, we discovered its role in the immune response. Through analyses of single-cell and GEO database data, we confirmed its involvement in immune cell regulation, specifically TAM activation. Subsequently, we conducted in vivo and in vitro experiments to confirm the involvement of RGS1 in polarizing M1 macrophages while indirectly regulating M2 macrophages through tumor cells. In conclusion, RGS1 could be a potential target for the transformation of chronic gastritis into gastric cancer and has a measurable impact on TAMs, which warrants further in-depth research.

Pediatric-inspired regimen for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: a prospective study from China.

Several international centers have used and reported pediatric-inspired regimens for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL). However, there is a lack of prospective data on the Chinese population. Herein, we performed a prospective study with a pediatric-inspired regimen (IH-2014 regimen) in treating adolescent and adult Ph- ALL patients in our center. From 2014 to 2021, a total of 415 patients aged between 14 and 65 years (median age, 27) were included in this study. After a median follow-up of 40.8 months, the 5-year overall survival, disease-free survival, and event-free survival rates were 53.8%, 51.1% and 45.0%, respectively. The regimen was generally well tolerated and safe, and the overall chemotherapy-related mortality was 3.6%. Age ≥ 40 years and persistent detectable minimal residual disease (MRD) post-induction were independent prognostic factors. Traditional risk factors for adult patients combined with MRD post-induction exhibit predictive significance for survival and relapse, which is helpful in the selection of subsequent treatment. Patients with high risk factors who can achieve deep MRD response after induction do not derive benefit from allogeneic hematopoietic stem cell transplantation.

HuangJinShuangShen granules can improve immunity and enhance the ability of 5-fluorouracil to induce apoptosis of gastric cancer cells.

In recent years, Chinese herbal compounds have gained significant prominence in the treatment of gastric cancer. The goal of this study was to investigate the antitumor effect of HuangJinShuangShen granules (HJSS) combined with 5-fluorouracil on MFC gastric cancer mice. In this study, the MFC model with gastric cancer was successfully established. After continuous administration for 14 d, the body weight, tumor volume and weight and spleen mass of mice in each group were recorded. The levels of IFN-γ and TGF-ß1 in serum were detected by ELISA. The expression of apoptosis proteins in tumor tissues was detected by Western blotting. Compared with the model group and the 5-FU group, the combined drug group can significantly inhibit tumor growth, reduce tumor volume, promote tumor cell necrosis and increase spleen index in mice. At the same time, the combined treatment group significantly increased IFN-γ level and BAX protein expression, decreased TGF-ß1 level and decreased Bcl2, Caspase-9 and Cleaved Caspase-3 protein expressions. These findings provide evidence that HJSS can augment the suppressive impact of 5-FU on tumor growth in gastric cancer mice, potentially through the induction of tumor cell apoptosis and the restoration of immune function.

A CH2CH3 hinge region enhances the cytotoxicity of anti-CD5 CAR-T cells targeting T cell acute lymphoblastic leukemia.

Chimeric antigen receptor T cell (CAR-T) therapies show considerable clinical efficacy in patients with B cell malignancies, but their efficacy is limited in patients with T cell acute lymphoblastic leukemia (T-ALL). CD5 is expressed on ∼85 % of malignant T cells, and CD5-targeting CAR-T cells can exhibit potent antitumor activity against T-ALL. However, optimization of CAR costimulatory endo-, hinge, and transmembrane domains could further increase their expansion and persistence, thereby enhancing their efficacy following exposure to tumor cells. Here we designed CD5-specific CARs with different molecular structures to generate CAR-T cells and investigated their anti-tumor efficacy in vitro and in vivo. CD5 CARs with a 4-1BB costimulatory domain (BB.z) or a CD28 costimulatory domain (28.z) exhibited specific cytotoxicity against CD5+ malignant cells in vitro. However, both failed to prolong the survival of T-ALL xenograft mice. Subsequently, we substituted the 28.z CAR hinge region with CH2CH3, which enhanced the ability of CH2CH3-CD5 CAR-T cells to specifically eradicate T-ALL cells in vitro and in vivo. Furthermore, patient-derived CH2CH3-CD5 CAR-T cells were generated which showed a marked killing effect of CD5-positive acute T-ALL cells in vitro. The anti-tumor activity of CD5 CAR-T cells with a CD28 co-stimulation domain and CH2CH3 hinge region was superior to those with BB.z and 28.z domains. These preclinical data provided new insights into the factors dictating efficacy in T-ALL treatment with CAR-T cells and hold promise for clinical translation.

Therapeutic effects against high-grade glioblastoma mediated by engineered induced neural stem cells combined with GD2-specific CAR-NK.

PURPOSE: High-grade glioblastoma is extremely challenging to treat because of its aggressiveness and resistance to conventional chemo- and radio-therapies. On the contrary, genetic and cellular immunotherapeutic strategies based on the stem and immune cells are emerging as promising treatments against glioblastoma (GBM). We aimed to developed a novel combined immunotherapeutic strategy to improve the treatment efficacy using genetically engineered PBMC-derived induced neural stem cells (iNSCs) expressing HSV-TK and second-generation CAR-NK cells against GBM. METHODS: iNSCs cells expressing HSV-TK (iNSCsTK) and GD2-specific CAR-NK92 (GD2NK92) were generated from PBMC-derived iNSCs and NK92 cell lines, respectively. The anti-tumor effect of iNSCsTK and the combinational therapeutics of iNSCsTK and GD2NK92 were evaluated by GBM cell line using in vitro and in vivo experiments. RESULTS: PBMC-derived iNSCsTK possessed tumor-tropism migration ability in vitro and in vivo, which exhibited considerable anti-tumor activity via bystander effect in the presence of ganciclovir (GCV). iNSCsTK/GCV could slow GBM progression and prolong median survival in tumor-bearing mice. However, the anti-tumor effect was limited to single therapy. Therefore, the combinational therapeutic effect of iNSCsTK/GCV and GD2NK92 against GBM was investigated. This approach displayed a more significant anti-tumor effect in vitro and in xenograft tumor mice. CONCLUSIONS: PBMC-derived iNSCsTK showed a significant tumor-tropic migration and an effective anti-tumor activity with GCV in vitro and in vivo. In addition, combined with GD2NK92, iNSCsTK therapeutic efficacy improved dramatically to prolong the tumor-bearing animal model's median survival.

[Clinical Analysis of SET-NUP214 Fusion Gene Positive Patients with Acute Leukemia].

OBJECTIVE: To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene. METHODS: The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively. RESULTS: Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive. CONCLUSION: The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.

GD2 CAR-T cells in combination with Nivolumab exhibit enhanced antitumor efficacy.

Glioblastoma (GBM) is a common primary brain tumor with poor clinical prognosis. Although CAR-T therapy has been trialed for treatment of GBM, the outcomes are sub-optimal possibly due to exhaustion of T cells and life-threatening neurotoxicity. To address these issues, a combined therapeutic strategy was tested in the current study using GD2 CAR-T together with Nivolumab - an anti-PD-1 monoclonal antibody. An effector-to-target co-culture system was established to evaluate the short-term and long-term cytotoxicity of CAR-T, as well as to investigate the inhibitory activity and T cell exhaustion associated with the PD-1/PD-L1 signaling pathway. Orthotopic NOD/SCID GBM animal models were generated to evaluate the safety and efficacy of the combined therapeutic strategy at various dosages of GD2 CAR-T with Nivolumab. GD2 CAR-T exhibited significant antigen-specific cytotoxicity in a dose-dependent manner in vitro. The persistence of cytotoxicity of GD2 CAR-T could be enhanced by addition of Nivolumab in the co-culture system. Animal studies suggested that GD2 CAR-T effectively infiltrated into tumor tissue and significantly hampered tumor progression. The optimal therapeutic outcome was obtained via using the medium dosage of CAR-T with Nivolumab, which displayed the highest efficacy in extending the survival up to 60 days. Further investigation of toxicity revealed that high-dosage of GD2 CAR-T could induce tumor apoptosis through p53/caspase-3/PARP signaling pathway. This study suggests that GD2 CAR-T in combination with Nivolumab may offer an improved therapeutic strategy for treatment of GBM.

Weierning, a Chinese patent medicine, improves chronic atrophic gastritis with intestinal metaplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Weierning tablet (WEN) is a traditional Chinese patent medicine widely used in clinical for chronic atrophic gastritis (CAG) therapy for years. However, the underlying mechanisms of WEN on anti-CAG are still unveiled. AIM OF THE STUDY: The present study aimed to elucidate the characteristic function of WEN on anti-CAG and to illuminate its potential mechanism. METHODS: The CAG model was established by gavage rats with a modeling solution (consisting of 2% sodium salicylate and 30% alcohol) with irregular diets and free access to 0.1% ammonia solution for two months on end. An enzyme-linked immunosorbent assay was used to measure the serum levels of gastrin, pepsinogen, and inflammatory cytokines. qRT-PCR was applied to measure mRNA expressions of IL-6, IL-18, IL-10, TNF-α, and γ-IFN in gastric tissue. Pathological changes and the ultrastructure of gastric mucosa were examined by hematoxylin and eosin staining and transmission electron microscopy, respectively. AB-PAS staining was applied to observe the intestinal metaplasia of gastric mucosa. Immunohistochemistry and Western blot were used to measure the expression levels of mitochondria apoptosis-related proteins and Hedgehog pathway-related proteins in gastric tissues. Expressions of Cdx2 and Muc2 protein were determined by immunofluorescent staining. RESULTS: WEN could dose-dependently lower the serum level of IL-1ß and the mRNA expressions of IL-6, IL-8, IL-10, TNF-α, and γ-IFN in gastric tissue. Also, WEN significantly alleviated the collagen deposition in gastric submucosa, regulated the expressions of Bax, Cleaved-caspase9, Bcl2, and Cytochrome c to reduce the apoptosis of gastric mucosa epithelial cells, and maintained the integrity of the gastric mucosal barrier. Moreover, WEN could reduce protein expressions of Cdx2, Muc2, Shh, Gli1, and Smo, and reverse intestinal metaplasia of gastric mucosa to block the progress of CAG. CONCLUSION: This study demonstrated a positive effect of WEN on improving CAG and reverse intestinal metaplasia. These functions were related to the suppression of gastric mucosal cells' apoptosis and the inhibition of Hedgehog pathways' activation.

Salviae miltiorrhiza against human lung cancer: A review of its mechanism (Review).

Lung cancer is one of the commonest malignant tumors in the world today, causing millions of mortalities every year. New methods to treat lung cancer are urgently needed. Salviae miltiorrhiza Bunge is a common Chinese medicine, often used for promoting blood circulation. In the past 20 years, Salviae miltiorrhiza has made significant progress in the treatment of lung cancer and is considered to be one of the most promising methods to fight against the disease. A great amount of research has shown that the mechanism of Salviae miltiorrhiza against human lung cancer mainly includes inhibiting the proliferation of lung cancer cells, promoting lung cancer cell apoptosis, inducing cell autophagy, regulating immunity and resisting angiogenesis. Research has shown that Salviae miltiorrhiza has certain effects on the resistance to chemotherapy drugs. The present review discussed the status and prospects of Salviae miltiorrhiza against human lung cancer.

Responses of microbial community to geochemical parameters on vertical depth in bioheap system of low-grade copper sulfide.

Monitoring of the microbial community in bioleaching system is essential for control process parameters and enhance the leaching efficiency. Due to the difficulty of sampling, microbial distribution, community succession and bioleaching activity along the vertical depth of bioleaching heaps remain unresolved. This study investigated the geochemical parameters and microbial community structure along a depth profile in a bioleaching heap and leachate. 80 ore samples at different heap depths and 9 leaching solution samples from three bioheaps of Zijin Copper Mine were collected. Microbial composition, mineral types and geochemical parameters of these samples were analyzed by 16S rRNA high-throughput sequencing and a series of chemical measurement technologies. The results revealed that the pH, Cu, Fe and the total sulfur contents were the major factors shaping the composition of the microbial communities in the bioleaching system. The extent of mineral oxidation increased as the sample depth increases, followed by the increasing of sulfur oxidizers. The abundance of sulfur and iron oxidizers including members of Acidithiobacillus, Sulfobacillus and Acidiferrobacter were significantly higher in the leaching heap than in the leaching solution, meanwhile, they showed strong positive interactions with other members within the same genera and iron oxidizer Leptospirillum and Ferroplasma. Besides, Acidithiobacillus negatively interacted with heterotrophs such as Sphingobium, Exiguobacterium, Brevundimonas and so on. On the contrast, members of Leptospirillum and unclassified Archaea were significantly abundant in the leaching solution and revealed strong interactions with members of Thermoplasmatales. The main conclusion of this study, especially the leaching potential of microorganisms prevailing in bioheaps and their relationships with geochemical factors, provides theoretical guidance for future process design such as the control of processing parameters and microbial community in heap leaching.

Treatment of STAT5b-RARA positive acute promyelocytic leukemia by Venetoclax combining with homoharringtonine, cytarabine: A case report and literature review.

Introduction: Acute promyelocytic leukemia (APL) is mostly due to the chromosome translocation t (15; 17) (q22; q12), leading to the formation of PML-RARA fusion protein. Some patients carried rare translocation involving RARA gene, who were called variant APL caused by RAR family (RARA, RARB, and RARG) and partner genes. STAT5b-RARA was a rare type of molecular genetic abnormality with unfavorable prognosis which have been reported in only 18 cases in variant APL. Knowledge of STAT5b-RARA (+) APL treatment is still limited. Case report: We presented a 38-year-old female variant APL case, who was STAT5b-RARA positive detected by reverse transcription polymerase chain reaction. The patient failed to respond after four-drug combined induction chemotherapy: idarubicin, cytarabine, all trans retinoic acid, and arsenic trioxide (As2O3). Then, the patient was re-induced with azacytidine, but still failed to achieve complete remission (CR). Next, she was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR. Later, the patient received hematopoietic stem cell transplantation after 4 cycles of consolidation therapy. Conclusion: Venetoclax combining with homoharringtonine and cytarabine has been used as the salvage therapy in the STAT5b-RARA positive APL successfully.