Ultrasensitive electrochemical sensor based on synergistic effect of Ag@MXene and antifouling cyclic multifunctional peptide for PD-L1 detection in serum.

A sensing interface co-constructed from the two-dimensional conductive material (Ag@MXene) and an antifouling cyclic multifunctional peptide (CP) is described. While the large surface area of Ag@MXene loads more CP probes, CP binds to Ag@MXene to form a fouling barrier and ensure the structural rigidity of the targeting sequence. This strategy synergistically enhances the biosensor's sensitivity and resistance to contamination. The SPR results showed that the binding affinity of the CP to the target was 6.23 times higher than that of the antifouling straight-chain multifunctional peptide (SP) to the target. In the 10 mg/mL BSA electrochemical fouling test, the fouling resistance of Ag@MXene + CP (composite sensing interface of CP combined with Ag@MXene) was 30 times higher than that of the bare electrode. The designed electrochemical sensor exhibited good selectivity and wide dynamic response range at PD-L1 concentrations from 0.1 to 50 ng/mL. The lowest detection limit was 24.54 pg/mL (S/N = 3). Antifouling 2D materials with a substantial specific surface area, coupled with non-straight chain antifouling multifunctional peptides, offer a wide scope for investigating the sensitivity and antifouling properties of electrochemical sensors.

Liposomal mitoxantrone-based multidrug chemotherapy as a bridge to allogeneic hematopoietic stem cell transplantation in relapsed/refractory acute lymphoblastic leukemia (ALL) after immunotherapy failure: a case report.

Acute lymphoblastic leukemia (ALL) represents a malignancy involving early-stage differentiated lymphoid cells that invade the bone marrow, blood, and extramedullary sites. First-line treatment spans 2-3 years with induction, consolidation, intensification, and long-term maintenance phases. Relapsed/refractory (R/R) ALL typically carries an adverse prognosis, and there is currently no standard of care for this disease. Here, we present a case of R/R ALL that responded effectively to liposomal mitoxantrone-based multidrug chemotherapy, resulting in a rapid complete response after 35 days of therapy. Subsequently, the patient was successfully treated with allo-HSCT. At 5 months follow-up, the patient was alive and leukemia-free. Additionally, no severe adverse events were recorded during liposomal mitoxantrone treatment or hospitalization for allo-HSCT. Given the encouraging efficacy and the manageable adverse events observed in our case, liposomal mitoxantrone-based multidrug chemotherapy should be further explored as a bridge to allo-HSCT in patients with R/R ALL.

Construction of a sensitive SWCNTs integrated SPR biosensor for detecting PD-L1+ exosomes based on Fe3O4@TiO2 specific enrichment and signal amplification.

Programmed cell death-ligand 1 positive (PD-L1+) exosomes play a crucial role in the realm of cancer diagnosis and treatment. Nevertheless, due to the intricate nature of biological specimens, coupled with the heterogeneity, low refractive index (RI), and scant surface coverage density of exosomes, traditional surface plasmon resonance (SPR) sensors still do not meet clinical detection requirements. This study utilizes the exceptional electrical and optical attributes of single-walled carbon nanotubes (SWCNTs) as the substrate for SPR sensing, thereby markedly enhancing sensitivity. Furthermore, sp2 hybridized SWCNTs have the ability to load specific recognition elements. Additionally, through the coordination interaction of Ti with phosphate groups and the ferromagnetism of Fe3O4, efficient exosomes isolation and enrichment in complex samples are achievable with the aid of an external magnetic field. Owing to the high-quality and high-RI of Fe3O4@TiO2, the response signal experiences amplification, thus further improving the performance of the SPR biosensor. The linear range of the SPR biosensor constructed by this method is 1.0 × 103 to 1.0 × 107 particles/mL, with a limit of detection (LOD) of 31.9 particles/mL. In the analysis of clinical serum samples, cancer patients can be differentiated from healthy individuals with an Area Under Curve (AUC) of 0.9835. This study not only establishes a novel platform for exosomes direct detection but also offers new perspectives for the sensitive detection of other biomarkers.

MiR-34a-5p suppresses cutaneous squamous cell carcinoma progression by targeting SIRT6.

Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor originating from epidermal or appendageal keratinocytes, with a rising incidence in recent years. Understanding the molecular mechanism driving its development is crucial. This study aims to investigate whether miR-34a-5p is involved in the pathogenesis of cSCC by targeting Sirtuin 6 (SIRT6).The expression levels of miR-34a-5p and SIRT6 were determined in 15 cSCC tissue specimens, 15 normal tissue specimens and cultured cells via real-time polymerase chain reaction (RT-qPCR). Pearson's correlation analysis was conducted to evaluate the relationship between miR-34a-5p and SIRT6 expression levels in cSCC tissues. A431 and SCL-1 cells were transfected with miR-34a-5p mimic, negative control or miR-34a-5p mimic together with recombinant plasmids containing SIRT6 gene. Cell counting kit-8, clone formation assay, wound healing assay, and flow cytometry were employed to assess the effects of these transfections on proliferation, migration, and apoptosis, respectively. The interaction between miR-34a-5p and SIRT6 was characterized using a dual-luciferase reporter assay.MiR-34a-5p expression was down-regulated in cSCC tissues significantly, while the SIRT6 expression was the opposite. A negative correlation was observed between the expression of miR-34a-5p and SIRT6 in cSCC tissues. Furthermore, overexpression of miR-34a-5p led to a significant reduction in the proliferation and migration abilities of A431 and SCL-1 cells, accompanied by an increase in apoptosis levels and a decrease in SIRT6 expression levels. MiR-34a-5p was identified as a direct target of SIRT6. Importantly, overexpression of SIRT6 effectively counteracted the inhibitory effect mediated by miR-34a-5p in cSCC cells.Our findings suggest that miR-34a-5p functions as a tumor suppressor in cSCC cells by targeting SIRT6.

PLCß4 driven by cadmium-exposure during gestation and lactation contributes to cognitive deficits by suppressing PIP2/PLCγ1/CREB/BDNF signaling pathway in male offspring.

The fetus and infants are particularly vulnerable to Cadmium (Cd) due to the immaturity of the blood-brain barrier. In utero and early life exposure to Cd is associated with cognitive deficits. Although such exposure has attracted widespread attention, its gender-specificity remains controversial, and there are no reports disclosing the underlying mechanism of gender­specific neurotoxicity. We extensively evaluated the learning and cognitive functions and synaptic plasticity of male and female rats exposed to maternal Cd. Maternal Cd exposure induced learning and memory deficits in male offspring rats, but not in female offspring rats. PLCß4 was identified as a critical protein, which might be related to the gender­specific cognitive deficits in male rats. The up-regulated PLCß4 competed with PLCγ1 to bind to PIP2, which counteracted the hydrolysis of PIP2 by PLCγ1. The decreased activation of PLCγ1 inhibited the phosphorylation of CREB to reduce BDNF transcription, which consequently resulted in the damage of hippocampal neurons and cognitive deficiency. Moreover, the low level of BDNF promoted AEP activation to induce Aß deposition in the hippocampus. These findings highlight that PLCß4 might be a potential target for the therapy of learning and cognitive deficits caused by Cd exposure in early life.

NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.

Low-Velocity Impact and Post-Impact Residual Flexural Properties of Kevlar/EP Three-Dimensional Angle-Interlock Composites.

In this study, five three-dimensional angle-interlock fabrics with different warp and weft densities were fabricated using 1000D Kevlar filaments. The Kevlar/EP composites were prepared by vacuum-assisted molding techniques. The low-velocity impact property of the composite was tested, focusing on the effects of the warp and weft densities, impact energy, impactor shape, and impactor diameter. The damage area, dent depth, and crack lengths in the warp and weft direction were used to evaluate the impact performance, and the specimens were compared with plain-weave composites with similar areal densities. The dominant failure mode of the conical impactor was fiber fracture, while the dominant failure mode of the hemispherical impactor was fiber-resin debonding. The cylindrical impactor showed only minor resin fragmentation. The residual flexural strength of the composite after impact was tested to provide insights into its mechanical properties. The study findings will provide a theoretical basis for the optimization of the design of impact-resistant structures using such materials and facilitate their engineering applications.

Targeting PRL phosphatases in hematological malignancies.

INTRODUCTION: Phosphatase of regenerating liver (PRL) family proteins, also known as protein tyrosine phosphatase 4A (PTP4A), have been implicated in many types of cancers. The PRL family of phosphatases consists of three members, PRL1, PRL2, and PRL3. PRLs have been shown to harbor oncogenic potentials and are highly expressed in a variety of cancers. Given their roles in cancer progression and metastasis, PRLs are potential targets for anticancer therapies. However, additional studies are needed to be performed to fully understand the roles of PRLs in blood cancers. AREAS COVERED: In this review, we will summarize recent studies of PRLs in normal and malignant hematopoiesis, the role of PRLs in regulating various signaling pathways, and the therapeutic potentials of targeting PRLs in hematological malignancies. We will also discuss how to improve current PRL inhibitors for cancer treatment. EXPERT OPINION: Although PRL inhibitors show promising therapeutic effects in preclinical studies of different types of cancers, moving PRL inhibitors from bench to bedside is still challenging. More potent and selective PRL inhibitors are needed to target PRLs in hematological malignancies and improve treatment outcomes.

Convenient preparation of indigo from the Ieaves of Baphicacanthus cusia(Nees) Bremek by enzymatic method and its MALDI-TOF-MS and UPLC-Q-TOF/MS analysis.

The manufacturing of indigo naturalis requires prolonged leaf soaking and lime stirring; the resulting indigo purity is less than 3.00% and the yield of indigo (measured in stems and leaves weight) is less than 0.50%, making it unsuitable for use in industrial procedures like printing and dyeing. An enzymatic method of creating indigo without the requirement for lime was investigated in order to generate high purity indigo. Single factor tests were performed to optimize the enzymatic preparation conditions. The findings showed that 60 °C, pH 5.5, 200 mL of leaves extract containing 0.45 mg/mL indican, and a 4:1 ratio of the acidic cellulose (activity: 9000 U/mL, liquid) to indican were the ideal parameters for enzymatic preparation. The yield of indigo was 40.32%, and the contents of indigo and indirubin were 37.37% and 2.30%, respectively. MALDI-TOF-MS in positive ion mode and UPLC-Q-TOF-MS in both positive and negative ion modes were used to analyze indigo extracts from Baphicacanthus cusia(Nees) Bremek by enzymatic preparation. It has been discovered that 13 alkaloids, 5 organic acids, 3 terpenoids, 3 steroids, 2 flavones, and 7 other compounds are present in indigo extracts. The presence of the indigo, indirubin, isorhamnetin, tryptanthrin, indigodole B, and indigodole C determined by UPLC-Q-TOF-MS was verified by MALDI-TOF-MS analysis. The enzymatic preparation of indigo extracts kept the same chemical makeup as conventional indigo naturalis. Thermal analysis and SEM morphology were used to confirm that there was no lime in the indigo extract. During the enzymatic process, Baphicacanthus cusia (Nees) Bremek was employed more effectively, increasing the yield and purity of indigo.

A case report of atypical chronic myeloid leukemia with complete hematological and major molecular response to Venetoclax/Azacitidine treatment.

Atypical Chronic Myeloid Leukemia (aCML), a myeloproliferative neoplasm with poor prognosis, was reclassified as aCML by the ICC classification, and as MDS/MPN with neutrophilia by the WHO 2022 classification. Due to the heterogeneity of its clinical features and the lack of unique biomarkers, as well as limited treatment options, aCML currently lacks a standardized treatment protocol. In this case report, we reviewed a young man diagnosed with aCML who achieved complete clinical and hematologic remission subsequent to receiving a therapeutic regimen combining Venetoclax and Azacitidine.

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. OBJECTIVE: This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. METHODS: The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. RESULTS: The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. STUDY LIMITATIONS: No animal experiments were conducted to further verify the results. CONCLUSION: Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

Enhanced photocatalytic ammonia oxidation over WO3@TiO2 heterostructures by constructing an interfacial electric field.

WO3 nanorods and xWO3@TiO2 (WO3/TiO2 mass ratio (x) = 1-5) photocatalysts were synthesized using the hydrothermal and sol-gel methods, respectively. The photocatalytic activities of xWO3@TiO2 for NH3 oxidation first increased and then decreased with a rise in TiO2 content. Among them, the heterostructured 3WO3@TiO2 photocatalyst showed the highest NH3 conversion (58 %) under the simulated sunlight irradiation, which was about two times higher than those of WO3 and TiO2. Furthermore, the smallest amounts of by-products (i.e., NO and NO2) were produced over 3WO3@TiO2. The enhancement in photocatalytic performance (i.e., NH3 conversion and N2 selectivity) of 3WO3@TiO2 was mainly attributed to the formed interfacial electric field between WO3 and TiO2, which promoted efficient separation and transfer of photogenerated charge carriers. Based on the results of reactive species trapping and active radical detection, photocatalytic oxidation of NH3 over 3WO3@TiO2 was governed by the photogenerated holes and superoxide radicals. This work combines two strategies of morphological regulation and interfacial electric field construction to simultaneously improve light utilization and photogenerated charge separation efficiency, which promotes the development of full-spectrum photocatalysts for the removal of ammonia.

[Clinical Analysis of Children with Thalassemia in Chongqing].

OBJECTIVE: To analyze the genotype distribution and hematological characteristics of children with thalassemia in Chongqing. METHODS: A total of 207 children with thalassemia admitted to Chongqing University Three Gorges Hospital from January 2021 to October 2022 were selected as the research objects. The genotype distribution and hematological characteristics were retrospectively analyzed. RESULTS: 207 cases of thalassemia were confirmed from 482 samples by gene detection, the detection rate was 42.95%, α-thalassemia accounted for 17.63%(85/482), ß-thalassemia accounted for 24.27%(117/482), and compound αß thalassemia accounted for 1.04%(5/482). A total of 5 gene mutation types of α-thalassaemia were detected in this study, which constituted 6 genotypes, αα/-SEA was the most common one, followed by αα/-α3.7. A total of 8 gene mutation types of ß-thalassemia were detected, which constituted 9 genotypes, the top three were CD17/N, CD654/N and CD41-42/N. The highest detection rate was found in the patients aged 0-3 years (57%), and the degree of anemia was mainly mild (88.41%). 97.58% of the patients were MCV< 80 fl, 98.55% were MCH< 28 pg, 60.87% were MCHC< 320 g/L, and 71.50% were RDW-SD < 37%. The MCV and MCH of ß-thalassemia group were lower than that of α-thalassemia group, and the MCHC was higher than that of α-thalassemia group (P <0.05), but RDW-SD was not significantly different between the two groups (P >0.05). There were no significant differences in MCV, MCH, MCHC and RDW-SD between ß+/ßN and ß0/ßN groups ( P >0.05). The MCV and RDW-SD of --/αα thalassemia group were lower than that in -α/αα thalassemia group, the differences were statistically significant (P < 0.05), but MCH and MCHC were not significantly different between the two groups (P >0.05). CONCLUSION: The genotypes of children with thalassemia in Chongqing are diverse and heterogeneous, and the majority of them are mild anemia. There are differences in haematological indexes among different genotypes of thalassemia.

2D MOF-enhanced SPR detector based on tunable supramolecular probes for direct and sensitive detection of DOX in serum.

Therapeutic drug monitoring of doxorubicin (DOX) is important to study pharmacokinetics in patients undergoing chemotherapy for reduction of side effects and improve patient survival by rationally controlling the dose of DOX. A fast and ultra-sensitive surface plasmon resonance (SPR) detector without sample pre-handling was developed for DOX monitoring. First, the two-dimensional metal-organic framework was modified on the Au film to enhance SPR, and then, the supramolecular probes with tunable cavity structure were self-assembled at the sensing interface for direct detection of DOX through specific host-guest interactions with a low detection limit of 60.24 pM. The precise monitoring of DOX in serum proved the possibility of clinical application with recoveries in the range 102.86-109.47%. The mechanisms of host-guest interactions between supramolecular and small-molecule drugs were explored in depth through first-principles calculations combined with SPR experiments. The study paves the way for designing facile and sensitive detectors and provides theoretical support and a new methodology for the specific detection of small molecules through calixarene cavity modulation.

Zishen Yutai Pills Promote Angiogenesis at the Maternal-Fetal Interface in Recurrent Spontaneous Abortion Mice by Regulating miR-187/VEGF Axis.

Ethnopharmacological Relevance: Zishen Yutai pills (ZYP), a traditional Chinese patent medicine, was listed in China in 1981. It is composed of 15 traditional Chinese medicines and has the effects of regulating menstruation, helping pregnancy, and preventing abortion. In clinical practice, it is effective in preventing habitual and threatened miscarriages, and continuing to explore its mechanism of action is very meaningful research. Aim of the Study: To explore the possible mechanism of ZYP promoting angiogenesis at the maternal-fetal interface in recurrent spontaneous abortion (RSA). Materials and Methods: In vitro experiments, placental trophoblast cells (PTCs) were isolated from the placental tissue of RSA mice and divided into six groups: Control group, Model group, ZYP group, miR-187 inhibitor NC group, miR-18 7 inhibitor group, and miR-187 inhibitor+ZYP group. Cell viability and cell cycle were measured using CCK8 and flow cytometry, respectively. The expression levels of miR-187, VEGF, VEGF-R1, and VEGF-R2 were measured using RT-qPCR, WB, and IF staining. Animal experiments first establish an RSA mice model (CBA/J × DBA/2) and then randomly divide the mice into four groups (n=10): normal pregnancy group, RSA model group, ZYP group, and progesterone capsule group. Observed the changes in embryo absorption rate, pathological morphology of decidual tissue, and ultrastructure of vascular endothelial cells in each group of mice. RT-qPCR, WB, and IF staining methods were used to determine the expression of miR-187, VEGF, VEGF-R1, and VEGF-R2. Results: In vitro, ZYP promoted the viability of PTCs and regulated their cell cycle, and ZYP down-regulated miR-187, up-regulated VEGF, VEGF-R1 and VEGF-R2 levels. miR-187 inhibitor showed the same effects, and further ZYP intervention enhanced the effects. In vivo, ZYP remarkably reduced embryo resorption rates, and improved the pathological morphology of decidual tissues and ultrastructure of vascular endothelial cells. Moreover, ZYP down-regulated miR-187, up-regulated VEGF, VEGF-R1 and VEGF-R2. Conclusion: In summary, ZYP can regulate the expression of VEGF via miR-187, then promote the angiogenesis at the maternal-fetal interface, and playing a therapeutic role in RSA.

Comparison of different preoperative objective nutritional indices for evaluating 30-d mortality and complications after liver transplantation.

BACKGROUND: The nutritional status is closely related to the prognosis of liver transplant recipients, but few studies have reported the role of preoperative objective nutritional indices in predicting liver transplant outcomes. AIM: To compare the predictive value of various preoperative objective nutritional indicators for determining 30-d mortality and complications following liver transplantation (LT). METHODS: A retrospective analysis was conducted on 162 recipients who underwent LT at our institution from December 2019 to June 2022. RESULTS: This study identified several independent risk factors associated with 30-d mortality, including blood loss, the prognostic nutritional index (PNI), the nutritional risk index (NRI), and the control nutritional status. The 30-d mortality rate was 8.6%. Blood loss, the NRI, and the PNI were found to be independent risk factors for the occurrence of severe postoperative complications. The NRI achieved the highest prediction values for 30-d mortality [area under the curve (AUC) = 0.861, P < 0.001] and severe complications (AUC = 0.643, P = 0.011). Compared to those in the high NRI group, the low patients in the NRI group had lower preoperative body mass index and prealbumin and albumin levels, as well as higher alanine aminotransferase and total bilirubin levels, Model for End-stage Liver Disease scores and prothrombin time (P < 0.05). Furthermore, the group with a low NRI exhibited significantly greater incidences of intraabdominal bleeding, primary graft nonfunction, and mortality. CONCLUSION: The NRI has good predictive value for 30-d mortality and severe complications following LT. The NRI could be an effective tool for transplant surgeons to evaluate perioperative nutritional risk and develop relevant nutritional therapy.

Vortex-blending matrix solid-phase dispersion and UPLC-Q-TOF/MS were proposed to extract and examine the urushiols from Toxicodendron vernicifluum bark.

Toxicodendron vernicifluum bark has been used for many years as a component in foods and as a traditional herbal medication. Unfortunately, the presence of urushiols, which induce allergies, limits its application. This study used a vortex-blending matrix solid-phase dispersion microextraction technique to extract urushiols from Toxicodendron vernicifluum bark. HPLC was used to evaluate the amounts of the extracted urushiols (15:0, 15:1, 15:2, and 15:3). The modified magnetic adsorbent was prepared through an in situ coprecipitation method and characterized using a variety of techniques. The optimized extraction conditions are as follows: using magnetic Zeolite Socony Mobil-Five as an adsorbent, a 1:2 sample/adsorbent ratio, 2.5 min of vortex-blending time, 4 mL of 0.1% (V/V) trifluoroacetic acid-methanol as the elution solvent and 8 min of ultrasound time. There was good linearity and high repeatability in the method. Furthermore, the limits of detection for the urushiols ranged from 0.20 to 0.50 µg/mL. Under the optimized conditions, 50 compounds were identified by ultra high performance liquid chromatography and quadrupole time-of-flight mass spectrometry. These compounds included 8 phenolic acids, 9 monomeric urushiols, 11 urushiol dimers, 10 other components, and 11 flavonoids. The suggested approach, which has the advantages of few stages and high extraction efficiency over existing extraction procedures, is a potentially useful method for obtaining and evaluating urushiols in raw materials or extracts.

Emerging potentials of Fe-based nanomaterials for chiral sensing and imaging.

Fe-based nanostructures have possessed promising properties that make it suitable for chiral sensing and imaging applications owing to their ultra-small size, non-toxicity, biocompatibility, excellent photostability, tunable fluorescence, and water solubility. This review summarizes the recent research progress in the field of Fe-based nanostructures and places special emphases on their applications in chiral sensing and imaging. The synthetic strategies to prepare the targeted Fe-based structures were also introduced. The chiral sensing and imaging applications of the nanostructures are discussed in details.

PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation.

Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells. IMPLICATIONS: Our studies uncover a novel mechanism that fine-tunes oncogenic KIT signaling in leukemia cells and will likely identify PRL2 as a novel therapeutic target in AML with KIT mutations.