Extreme Medialized Repair for Challenging Large and Massive Rotator Cuff Tears Reveals Healing and Significant Functional Improvement.

PURPOSE: To evaluate range of motion, muscle strength, clinical outcomes, and radiographic results of the extreme medialized procedure on rotator cuff tears that were initially irreparable. METHODS: From arthroscopic rotator cuff repair cases performed at our institution (June 2017 and August 2020), we retrospectively reviewed cases in which the rotator cuff was (1) unable to be withdrawn to the greater tuberosity, (2) repaired using the extreme medialized procedure, and (3) followed up for a minimum of 2 years. Patients with a history of previous surgery were excluded. Preoperative and postoperative scores were used for clinical evaluation. Imaging evaluation used 2-year postoperative magnetic resonance (MR) images. RESULTS: Sixty-four patients met the criteria; mean age 68.2 ± 7.9 (range 51-82) years; mean follow-up period 26 ± 2 (24-37) months. Tear size: 45 ± 7.1 (30-70) mm in medial to lateral diameters, 40 ± 9.3 (30-60) mm in anteroposterior diameter; suture anchor number: 5.5 ± 1.2 (4-8). The visual analog scale score (50.7 to 11.8), the University of California, Los Angeles, score (12 to 31), constant score (45 to 31), and the American Shoulder and Elbow Surgeons score (53 to 31) at the final follow-up improved compared with preoperative values (all P < .0001). Preoperative and postoperative changes in range of motion also showed improvement in anterior elevation (107° to 151°, P < .0001), abduction (100° to 154°, P < .0001), external rotation (41° to 47°, P = .0238), and internal rotation (L1 to Th10, P < .0001). Muscle strength was also improved in abduction (from 1.9 kg to 5.0 kg, P < .0001) and external rotation (from 3.5 kg to 7.7 kg, P < .0001). MR imaging evaluation revealed 2 cases (3.1%) of retears that fell into type 4 Sugaya classification. CONCLUSIONS: Extremely medialized repair of large and massive tears not able to be repaired using conventional techniques led to improved clinical outcomes compared to preoperative conditions. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Prevalence and predisposing factors of neuropathic pain in patients with rotator cuff tears.

BACKGROUND: The management of pain in patients with rotator cuff tears can be challenging. Neuropathic pain is reportedly associated with pain occurrence in musculoskeletal diseases. However, to date, few studies have reported on the prevalence of neuropathic pain in patients with rotator cuff tears or identified the factors associated with neuropathic pain in a multicenter study. METHODS: A total of 391 patients (205 males and 186 females; median age, 67.7 years; range, 27-92 years) with rotator cuff tears were included in this study. The prevalence of neuropathic pain in rotator cuff tears was investigated using the Japanese version of the painDETECT questionnaire for all patients. In addition, factors significantly associated with the occurrence of neuropathic pain were examined using multivariate logistic regression analysis. RESULTS: Twenty-eight patients (7.2%) were classified into the neuropathic pain group (score ≥19), 97 (24.8%) into the uncertainty regarding neuropathy group (score 13-18), and 266 (68.0%) into the nociceptive pain group (score ≤12). According to the multivariate logistic regression analysis, the independent predictors of neuropathic pain were the VAS score (most severe pain during the past 4 weeks; odds ratio, 1.55; 95% confidence interval [CI], 1.23-2.09) and UCLA shoulder score (odds ratio, 0.81; 95% CI, 0.65-0.97). CONCLUSIONS: Based on the study findings, the prevalence of neuropathic pain in patients with rotator cuff tear was 7.2%. It is important to investigate the presence or absence of neuropathic pain when treating patients with painful rotator cuff tears, because neuropathy associated with rotator cuff tears may adversely affect patient outcomes.

Comparison of cryoprotectants in hematopoietic cell infusion-related adverse events.

BACKGROUND: The standard cryoprotectant for human cellular products is dimethyl sulfoxide (DMSO), which is associated with hematopoietic cell infusion-related adverse events (HCI-AEs) in hematopoietic stem cell transplantation including peripheral blood stem cell (PBSC) transplantation (PBSCT). DMSO is often used with hydroxyethyl starch (HES), which reduces DMSO concentration while maintaining the postthaw cell recovery. The cryoprotectant medium CP-1 (Kyokuto Pharmaceutical Industrial) is widely used in Japan. After mixture of a product with CP-1, DMSO and HES concentrations are 5% and 6%, respectively. However, the safety profile of CP-1 in association with HCI-AEs has not been investigated. STUDY DESIGN AND METHODS: To compare CP-1 with other cryoprotectants, we conducted a subgroup analysis of PBSCT recipients in a prospective surveillance study for HCI-AEs. Moreover, we validated the toxicity of CP-1 in 90 rats following various dose administration. RESULTS: The PBSC products cryopreserved with CP-1 (CP-1 group) and those with other cryoprotectants, mainly 10% DMSO (non-CP-1 group), were infused into 418 and 58 recipients, respectively. The rate of ≥grade 2 HCI-AEs was higher in the CP-1 group, but that of overall or ≥grade 3 HCI-AEs was not significantly different, compared to the non-CP-1 group. Similarly, after propensity score matching, ≥grade 2 HCI-AEs were more frequent in the CP-1 group, but the ≥grade 3 HCI-AE rate did not differ significantly between the groups. No significant toxicity was detected regardless of the CP-1 dose in the 90 rats. CONCLUSIONS: Infusion of a CP-1-containing PBSC product is feasible with the respect of HCI-AEs.

Stump classification was correlated with retear in the suture-bridge and double-row repair techniques for arthroscopic rotator cuff repair.

PURPOSE: The Stump classification is significantly correlated with a retear after arthroscopic rotator cuff repair. However, no study has evaluated whether or not the stump classification is correlated with retear in the suture-bridge or double-row repair techniques. The aim of this study was to evaluate the relationship between a retear and the stump classification in the suture-bridge and double-row repair techniques. METHODS: Among 389 patients who underwent arthroscopic repairs of full-thickness rotator cuff tears using suture-bridge or double-row repair techniques, 326 patients (median age 67.0 years; range 25-85) were included. There were 51 small, 172 medium, 83 large, and 20 massive tears. Two hundred forty patients were treated with the suture-bridge technique, and 86 patients were treated with the double-row technique. The following variables were analyzed: age, sex, the Cofield classification, anteroposterior and mediolateral tear size on preoperative MRI, global fatty degeneration index, and the stump classification. Cuff integrity was evaluated on magnetic resonance imaging at 6 months after surgery. The patients were divided into the intact and retear groups and the relationship between the variables and retear was evaluated by multivariate logistic regression analysis. RESULTS: The overall retear rate was 10.1%. In the multivariate logistic regression analysis, the independent predictors of a retear were the stump classification type 3 (Odds ratio: 4.71, p = 0.0246), global fatty degeneration index (Odds ratio: 3.87, p = 0.0030), and anteroposterior tear size (Odds ratio: 1.07, p = 0.0077) in the suture bridge technique. In the double-row technique, the independent predictors of retear were stump classification type 3 (Odds ratio: 7.82, p = 0.0348), and age (Odds ratio: 1.22, p = 0.0163). CONCLUSION: The stump classification was significantly correlated with retear in the suture-bridge and double-row repair technique. Stump classification type 3 was indicated to be an important risk factor for predicting retear. LEVEL OF EVIDENCE: III.

[Examination of Application to Radiation Protection Education by Four-dimensional Visualization of Scatter Distribution in Radiological Examination Using Virtual Reality].

PURPOSE: When working on fluoroscopy and patient assistance in a healthcare facility, workers need to understand how to properly protect scattered radiation. In this study, we examined a four-dimensional visualization method to make it easy to understand the spread of scattered radiation visually, and proposed its application to radiation protection education. METHODS: We constructed the X-ray room, X-ray CT room, and angiography room using Particle Heavy Ion Transport code System (PHITS), and calculated the scattered radiation distribution when the patient was irradiated with X-rays. The three-dimensional distribution of each moment was continuously displayed to create a four-dimensional distribution. Using the created data, we conducted radiation protection education including exercises to make the students confirm the scatter distribution from any direction. The effectiveness of the scattered radiation visualization data was evaluated by a questionnaire. RESULTS: The position of assistance for standing chest radiograph was less scattered radiation at the side and below the patient. As a result of the questionnaire, this education has confirmed the effect of attracting attention about radiation protection. The fourdimensional visualization allowed students to understand the behavior of radiation and the source of scattered radiation. CONCLUSION: Visualization of three- and four-dimensional scattered radiation distribution in the radiological examination room can intuitively enhance the understanding of the invisible radiation spread and appropriate aids.

Autocrine and Paracrine Interactions between Multiple Myeloma Cells and Bone Marrow Stromal Cells by Growth Arrest-specific Gene 6 Cross-talk with Interleukin-6.

The pathogenesis of multiple myeloma (MM) has not yet been fully elucidated. Our microarray analysis and immunohistochemistry revealed significant up-regulation of growth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein with a structural homology with protein S, in bone marrow (BM) cells of MM patients. ELISA showed that the serum levels of soluble Gas6 were significantly increased in the MM patients when compared with healthy controls. Gas6 was overexpressed in the human CD138-positive MM cell line RPMI-8226. Exogenous Gas6 suppressed apoptosis induced by serum deprivation and enhanced cell proliferation of the MM cells. The conditional medium from the human BM stromal cell line HS-5 induced cell proliferation and anti-apoptosis of the MM cells with extracellular signal-regulated kinase, Akt, and nuclear factor-κB phosphorylation, which were reversed by the neutralizing antibody to Gas6 or IL-6. The TAM family receptor Mer, which has been identified as a Gas6 receptor, was overexpressed in BM cells of MM patients. The knockdown of Mer by siRNA inhibited cell proliferation, anti-apoptosis, and up-regulation of intercellular cell adhesion molecule-1 (ICAM-1) in MM cells stimulated by an HS-5 cell-conditioned medium. Furthermore, the Gas6-neutralizing antibody reduced the up-regulation of IL-6 and ICAM-1 induced by a HS-5 cell-conditioned medium in MM cells. The present study provides new evidence that autocrine and paracrine stimulation of Gas6 in concert with IL-6 contributes to the pathogenesis of MM, suggesting that Gas6-Mer-related signaling pathways may be a promising novel target for treating MM.

Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model.

Neuropathic pain after spinal surgery, so-called failed back surgery syndrome, is a frequently observed common complication. One cause of the pain is scar tissue formation, observed as post-surgical epidural adhesions. These adhesions may compress surrounding spinal nerves, resulting in pain, even after successful spinal surgery. E8002 is an anti-adhesive membrane. In Japan, a clinical trial of E8002 is currently ongoing in patients undergoing abdominal surgery. However, animal experiments have not been performed for E8002 in spinal surgery. We assessed the anti-adhesive effect of E8002 in a rat laminectomy model. The dura matter was covered with an E8002 membrane or left uncovered as a control. Neurological evaluations and histopathological findings were compared at six weeks postoperatively. Histopathological analyses were performed by hematoxylin⁻eosin and aldehyde fuchsin-Masson Goldner staining. Three assessment areas were selected at the middle and margins of the laminectomy sites, and the numbers of fibroblasts and inflammatory cells were counted. Blinded histopathological evaluation revealed that adhesions and scar formation were reduced in the E8002 group compared with the control group. The E8002 group had significantly lower numbers of fibroblasts and inflammatory cells than the control group. The present results indicate that E8002 can prevent epidural scar adhesions after laminectomy.

Olanzapine promotes the accumulation of lipid droplets and the expression of multiple perilipins in human adipocytes.

Second generation antipsychotics are useful for the treatment of schizophrenia, but concerns have been raised about the side effects of diabetes mellitus and obesity. Olanzapine, especially, is associated with more weight gain than the others. It has been reported that olanzapine promotes adipocyte-differentiation in rodents both in vivo and in vitro. In this study the effects of antipsychotics on human adipocytes were investigated by using human mesenchymal stem cells (hMSCs). When hMSCs were differentiated and treated with various antipsychotics, olanzapine and clozapine increased intracellular lipids. Olanzapine induced lipid accumulation in a dose-dependent manner. Proteomic analysis revealed that PLIN4 and several enzymes for lipid metabolism were increased in the hMSCs after olanzapine treatment. During adipocyte differentiation, olanzapine increased the protein expression of PLIN1, PLIN2 and PLIN4. These proteins are known to be associated with the initial stage of lipid droplet formation. Immunocytochemistry showed that olanzapine increased and enlarged the lipid droplets coated with PLIN1 and PLIN2 while PLIN4 was largely distributed in the cytosol. mRNA expression of PLIN2, but not PLIN1 or PLIN4, was increased by olanzapine. On the other hand, olanzapine did not alter the mRNA level of transcription regulators involved in adipocyte-differentiation or adipokines. The present study shows that olanzapine induced transient PLIN2 expression in hMSCs that could result in an accumulation of lipid droplets and overexpression of PLIN1 and PLIN4, providing information of possible interest for olanzapine-induced weight gain.

Modified ESHAP regimen for relapsed/refractory T cell lymphoma: a retrospective analysis.

Peripheral T cell lymphomas account for approximately 10 % of all the non-Hodgkin lymphomas and are characterized by an aggressive clinical course and poor treatment outcome. In contrast to the improvement in the treatment of B cell lymphomas, there is no established standard chemotherapy regimen for relapsed/refractory T cell lymphomas. Our institute introduced modified ESHAP (mESHAP) regimen to reduce renal toxicity of standard ESHAP therapy, in which cisplatin was switched to carboplatin. We retrospectively analyzed the efficacy of mESHAP against relapsed/refractory T cell lymphomas. Twenty-two patients with relapsed/refractory T cell lymphomas were treated with mESHAP regimen at the University of Tokyo Hospital between January 2001 and December 2012. The median age was 59 years (range, 36-77). The diagnosis comprised peripheral T cell lymphoma, not otherwise specified (n = 10), angioimmunoblastic T cell lymphoma (AITL; n = 9), mycosis fungoides (n = 1), and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (n = 2). The median follow-up period was 9.5 months (range, 2.5-62.3). Complete remission (CR) was achieved in four patients (18 %) and partial remission (PR) in three patients (14 %). The median overall survival (OS) and progression-free survival (PFS) were 11.0 and 2.5 months, respectively. Leukopenia was the most frequent side effect and renal impairment was rare. According to a multivariate analysis, better OS and PFS were recorded in patients without bone marrow invasion (OS, hazard ratio (HR) 0.13, p = 0.0079; PFS, HR 0.13, p = 0.0044) or those with AITL (OS, HR 0.21, p = 0.021; PFS, HR 0.15, p = 0.0043). Although overall outcomes of mESHAP for relapsed/refractory T cell lymphomas were not excellent, this regimen remains one of the possible candidates for those with AITL histology or without bone marrow invasion.

CD4+ T cells in aged or thymectomized recipients of allogeneic stem cell transplantations.

BACKGROUND: CD4+CD25highFOXP3+ regulatory T (Treg) cells, which include thymus-derived and peripherally induced cells, play a central role in immune regulation, and are therefore crucial to prevent graft-versus-host disease (GVHD). The increasing use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with thymus regression, and our case of allo-HSCT shortly after total thymectomy, raised questions about the activity of thymus-derived Treg cells and peripherally induced Treg cells, which are otherwise indistinguishable. RESULTS: We found that despite pre-transplant thymectomy or older age, both naïve and effector Treg cells, as well as naïve and effector conventional T cells, proliferated in allo-HSCT recipients. Higher proportions of total Treg cells 1 month post allo-HSCT, and naïve Treg cells 1 year post allo-HSCT, appeared in patients achieving complete chimera without developing significant chronic GVHD, including our thymectomized patient, compared with patients who developed chronic GVHD. CONCLUSIONS: Treg cells that modulate human allogeneic immunity may arise peripherally as well as in the thymus of allo-HSCT recipients.

Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell of mixed lineage leukemia fusion leukemia through upregulation of p16.

Leukemia stem cells (LSC) are resistant to conventional chemotherapy and persistent LSC after chemotherapy are supposed to be a major cause of relapse. However, information on genetic or epigenetic regulation of stem cell properties is still limited and LSC-targeted drugs have scarcely been identified. Epigenetic regulators are associated with many cellular processes including maintenance of stem cells. Of note are polycomb group proteins, because they potentially control stemness, and can be pharmacologically targeted by a selective inhibitor (DZNep). Therefore, we investigated the therapeutic potential of EZH2 inhibition in mixed lineage leukemia (MLL) fusion leukemia. Intriguingly, EZH2 inhibition by DZNep or shRNA not only suppressed MLL fusion leukemia proliferation but also reduced leukemia initiating cells (LIC) frequency. Expression analysis suggested that p16 upregulation was responsible for LICs reduction. Knockdown of p16 canceled the survival advantage of mice treated with DZNep. Chromatin immunoprecipitation assays demonstrated that EZH2 was highly enriched around the transcription-start-site of p16, together with H3K27 methylation marks in MLL/ENL and Hoxa9/Meis1 transduced cells but not in E2A/HLF transduced cells. Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggest that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression, because expression levels of Hoxa9 and p16 were not inversely related between MLL/ENL and Hoxa9/Meis1 transduced cells. In summary, our findings show that EZH2 is a potential therapeutic target of MLL fusion leukemia stem cells.

Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples.

Induced pluripotent stem cells (iPSCs) can be generated by the expression of defined transcription factors not only from normal tissue, but also from malignant cells. Cancer-derived iPSCs are expected to provide a novel experimental opportunity to establish the disease model. We generated iPSCs from imatinib-sensitive chronic myelogenous leukemia (CML) patient samples. Remarkably, the CML-iPSCs were resistant to imatinib although they consistently expressed BCR-ABL oncoprotein. In CML-iPSCs, the phosphorylation of ERK1/2, AKT, and JNK, which are essential for the maintenance of both BCR-ABL (+) leukemia cells and iPSCs, were unchanged after imatinib treatment, whereas the phosphorylation of signal transducer and activator of transcription (STAT)5 and CRKL was significantly decreased. These results suggest that the signaling for iPSCs maintenance compensates for the inhibition of BCR-ABL. CML-iPSC-derived hematopoietic cells recovered the sensitivity to imatinib although CD34(+)38(-)90(+)45(+) immature cells were resistant to imatinib, which recapitulated the pathophysiologic feature of the initial CML. CML-iPSCs provide us with a novel platform to investigate CML pathogenesis on the basis of patient-derived samples.

Three-dimensional analyses of proximal humeral fractures using computed tomography with multiplanar reconstruction: early stability of fixation after osteosynthesis in relation to preoperative bone quality.

The purpose of this study was to evaluate the relationship between the bone quality of the humeral head measured by CT multiplanar reconstruction images (MPR) and the stability of nail or plate fixation and to compare the clinical outcomes of these procedures in patients with proximal humeral fractures. Thirty-six consecutive patients (nail group: n = 18, plate group: n = 18) were investigated. In nail group, 14 cases were classified as two-part fractures, three cases were classified as three-part fractures and one case was classified as four-part fractures. In plate group, three cases were classified as two-part fractures, nine cases were classified as three-part fractures and six cases were classified as four-part fractures. Both clinical and radiological outcomes were assessed. In addition, the percentage of trabecular bone volume of the humeral head was calculated using preoperative CT-MPR images. Three patients in the nail group underwent reoperation. In contrast, no patients in the plate group underwent reoperation. In nail group, six of 18 (33%) patients demonstrated poor results (three underwent reoperation, and three had varus displacements >10º) and had bone volume percentages (axial image) that were significantly lower than those observed in the patients with good results. The cutoff point of trabecular bone volume required to obtain satisfactory results after surgical treatment using intramedullary nail was 78%. The results of this study suggest that the bone volume of the humeral head calculated using CT-MPR images provides useful information, in addition to the type of fracture, when selecting fixation devices for osteosynthesis of proximal humeral fracture.

Cellular carcinogenesis in preleukemic conditions:drivers and defenses.

Acute myeloid leukemia (AML) arises from preleukemic conditions. We have investigated the pathogenesis of typical preleukemia, myeloproliferative neoplasms, and clonal hematopoiesis. Hematopoietic stem cells in both preleukemic conditions harbor recurrent driver mutations; additional mutation provokes further malignant transformation, leading to AML onset. Although genetic alterations are defined as the main cause of malignant transformation, non-genetic factors are also involved in disease progression. In this review, we focus on a non-histone chromatin protein, high mobility group AT-hook2 (HMGA2), and a physiological p53 inhibitor, murine double minute X (MDMX). HMGA2 is mainly overexpressed by dysregulation of microRNAs or mutations in polycomb components, and provokes expansion of preleukemic clones through stem cell signature disruption. MDMX is overexpressed by altered splicing balance in myeloid malignancies. MDMX induces leukemic transformation from preleukemia via suppression of p53 and p53-independent activation of WNT/ß-catenin signaling. We also discuss how these non-genetic factors can be targeted for leukemia prevention therapy.

Prospects and Potential for Chimerism Analysis after Allogeneic Hematopoietic Stem Cell Transplantation.

Chimerism analysis after allogeneic hematopoietic stem cell transplantation serves to confirm engraftment, indicate relapse of hematologic malignancy, and attribute graft failure to either immune rejection or poor graft function. Short tandem repeat PCR (STR-PCR) is the prevailing method, followed by quantitative real-time PCR (qPCR), with detection limits of 1-5% and 0.1%, respectively. Chimerism assays using digital PCR or next-generation sequencing, both of which are more sensitive than STR-PCR, are increasingly used. Stable mixed chimerism is usually not associated with poor outcomes in non-malignant diseases, but recipient chimerism may foretell relapse of hematologic malignancies, so higher detection sensitivity may be beneficial in such cases. Thus, the need for and the type of intervention, e.g., immunosuppression regimen, donor lymphocyte infusion, and/or salvage second transplantation, should be guided by donor chimerism in the context of the feature and/or residual malignant cells of the disease to be treated.

Two Japanese Pediatric Patients With Primary Ciliary Dyskinesia Caused by Loss-of-Function Variants in the CCNO gene.

Primary ciliary dyskinesia (PCD) is a rare congenital disorder caused by pathogenic variants of genes related to cilia. Here, we report two Japanese pediatric patients with PCD caused by pathogenic compound heterozygous variants in the cyclin O (CCNO) gene (Case 1, NM_021147.4:c.[262C>T];[781delC], p.[Gln88Ter];[Leu261fs]; Case 2, c.[262C>T];[c.248_252dupTGCCC], p.[Gln88Ter];[Gly85fs]). The clinical symptoms of the patients were varied. Neither of the patients had situs inversus. Transmission electron microscopy of the respiratory cilia from the nasal mucosa in Case 1 showed a remarkable reduction of cilia and the few residual cilia had central pair defects and microtubular disorganization.

Murine double minute X plays a central role in leukemic transformation and may be a promising target for leukemia prevention strategies.

Acute myeloid leukemia (AML) is a fatal disease resulting from preleukemic hematopoietic conditions, including asymptomatic clonal hematopoiesis. The accumulation of genetic changes is one of the causes of leukemic transformation. However, nongenetic factors, including the overexpression of specific genes also contribute to preleukemic to leukemic transition. Among them, the p53 inhibitor murine double minute X (MDMX) plays crucial roles, especially in leukemia initiation. MDMX is broadly overexpressed in the vast majority of AML cases, including in hematopoietic stem/progenitor cell (HSPC) level. Recently, high expression of MDMX in HSPC has been shown to be associated with leukemic transformation in patients with myelodysplastic syndromes, and preclinical studies have demonstrated that MDMX overexpression accelerates the transformation of preleukemic murine models, including models of clonal hematopoiesis. MDMX inhibition, through activation of cell-intrinsic p53 activity, shows antileukemic effects. However, the molecular mechanisms of MDMX in provoking leukemic transformation are complicated. Both p53-dependent and -independent mechanisms are involved in the progression of the disease. This review discusses the canonical and noncanonical functions of MDMX and how these functions are involved in the maintenance, expansion, and progression to malignancy of preleukemic stem cells. Moreover, strategies on how leukemic transformation could be prevented by targeting MDMX in preleukemic stem cells are discussed.

Impaired Repopulating Ability of Uhrf2-/- Hematopoietic Progenitor Cells in Mice.

UHRF proteins catalyze the ubiquitination of target proteins and are involved in regulating gene expression. Some studies reported a reduced expression of UHRF2 in acute leukemia cells, but the role of UHRF2 in hematopoiesis remains unknown. Here, we generated Uhrf2-/- mice to clarify the role of UHRF2 deletion in hematopoiesis. Compared to Uhrf2+/+ mice, Uhrf2-/- mice showed no differences in complete blood counts, as well as bone marrow (BM) findings and spleen weights. Proportions of cells in progenitor fractions in BM were comparable between Uhrf2+/+ mice and Uhrf2-/- mice. However, in competitive repopulation assays with BM transplants (BMT), the proportions of Uhrf2-/- cells were decreased relative to Uhrf2+/+ cells in all lineages. After the second BMT, Uhrf2-/- neutrophils were few, while 20-30% of Uhrf2-/- T cells and B cells were still detected. RNA sequencing showed downregulation of some genes associated with stem-cell function in Uhrf2-/- hematopoietic stem/progenitor cells (HSPCs). Interestingly, trimethylated histone H3 lysine 9 was increased in Uhrf2-/- HSPCs in a cleavage under targets and tagmentation assay. While UHRF2 deletion did not cause hematologic malignancy or confer a growth advantage of HSPCs, our results suggest that UHRF2 may play a role in the regulation of hematopoiesis.