Design of soft x-ray varied-line-spacing (VLS) high-dispersion laminar-type grating coated with super-mirror-type (SMT) multilayer for flat-field spectrograph in a region of 2-4 keV.

A soft x-ray varied-line-spacing (VLS) laminar-type spherical grating with a super-mirror-type (SMT) multilayer was designed for a soft x-ray high resolution flat-field spectrograph in a region of 2-4 keV. The effective groove density of the designed VLS grating is 3200 lines/mm, and the local groove density varies from 2700 to 3866 lines/mm. The geometrical imaging property was evaluated by numerical calculations. The resolving power estimated by means of ray tracing was up to ∼103. For the evaluation of diffraction efficiency, the SMT multilayer structure designed for 3200 lines/mm in our previous work, Koike et al., Rev. Sci. Instrum. 94, 045109 (2023), was employed, and the numerical calculation was performed considering the local groove density of VLS grooves and the local incidence angle being affected by the curvature of the spherical surface and the geometrical relation between the source and incidence point on the grating. The results showed that the SMT multilayer-coated grating exhibited about an order of magnitude higher diffraction efficiency compared with an Au-coated grating.

Design of soft x-ray laminar-type gratings coated with supermirror-type multilayer to enhance diffraction efficiency in a region of 2-4 keV.

Soft x-ray diffraction gratings coated with a supermirror-type multilayer were designed to enhance diffraction efficiency in the energy range of 2-4 keV by means of numerical calculations. The optimized groove depth and incidence angle are 2.05 nm and 88.65°, respectively, for the grating having a groove density of 3200 grooves/mm. Regarding the multilayer structure, the optimum number of B4C/W layers pair was 11 and the thickness of B4C was increased from bottom to top, while that of W was kept constant. The replacement of the top layer of W by either Co, Cr, or Ni was an effective means of obtaining uniform diffraction efficiency. In the region of 2-4 keV, the calculated diffraction efficiency of the designed gratings was up to ∼5.3%, on average, and almost eight times larger than that of ∼0.7% of an Au coated grating.

Proof-of-Principle Experiment for Testing Strong-Field Quantum Electrodynamics with Exotic Atoms: High Precision X-Ray Spectroscopy of Muonic Neon.

To test bound-state quantum electrodynamics (BSQED) in the strong-field regime, we have performed high precision x-ray spectroscopy of the 5g-4f and 5f- 4d transitions (BSQED contribution of 2.4 and 5.2 eV, respectively) of muonic neon atoms in the low-pressure gas phase without bound electrons. Muonic atoms have been recently proposed as an alternative to few-electron high-Z ions for BSQED tests by focusing on circular Rydberg states where nuclear contributions are negligibly small. We determined the 5g_{9/2}- 4f_{7/2} transition energy to be 6297.08±0.04(stat)±0.13(syst) eV using superconducting transition-edge sensor microcalorimeters (5.2-5.5 eV FWHM resolution), which agrees well with the most advanced BSQED theoretical prediction of 6297.26 eV.

Deexcitation Dynamics of Muonic Atoms Revealed by High-Precision Spectroscopy of Electronic K X Rays.

We observed electronic K x rays emitted from muonic iron atoms using superconducting transition-edge sensor microcalorimeters. The energy resolution of 5.2 eV in FWHM allowed us to observe the asymmetric broad profile of the electronic characteristic Kα and Kß x rays together with the hypersatellite K^{h}α x rays around 6 keV. This signature reflects the time-dependent screening of the nuclear charge by the negative muon and the L-shell electrons, accompanied by electron side feeding. Assisted by a simulation, these data clearly reveal the electronic K- and L-shell hole production and their temporal evolution on the 10-20 fs scale during the muon cascade process.

Scoring System to Predict pt2 in Gallbladder Cancer Based on Carcinoembryonic Antigen and Tumor Diameter.

BACKGROUND AND AIMS: T2 gallbladder cancer requires lymph node dissection for curative resection, whereas simple cholecystectomy is adequate to treat T1 gallbladder cancer. Hence, this study aimed to develop an accurate scoring system to preoperatively predict pT2 in gallbladder cancer. MATERIAL AND METHODS: We retrospectively assessed data from 57 patients with suspected gallbladder cancer who underwent curative resection between September 2003 and May 2017. Six with apparent invasion of adjacent organs on preoperative images were excluded. We evaluated preoperative computed tomography, magnetic resonance and endoscopic ultrasonographic images, blood biochemistry, and the maximum standard uptake value in fluorodeoxyglucose-positron emission tomography images. We analyzed whether correlations between preoperative findings and the depth of tumor invasion could predict pT2. RESULTS: The pathological diagnosis was gallbladder cancer in 30 (58.8%) patients, of whom 21 (69.9%) had pT2 or worse. Multivariate analyses selected carcinoembryonic antigen and tumor diameter as independent predictors of pT2 or worse (odds ratios = 1.741 and 1.098, respectively; 95% confidence intervals = 1.004-3.020 and 1.008-1.197, respectively). A regression formula was created using carcinoembryonic antigen and tumor diameter to calculate pT2 predictive scores. The area under the receiver operating characteristics curve of the pT2 predictive score was 0.873. CONCLUSION: We created a scoring system to predict pT2 in gallbladder cancer using carcinoembryonic antigen and tumor diameter. The present findings suggested that carcinoembryonic antigen is important for the preoperative evaluation of gallbladder cancer.

Enhancement of breast cancer on pre-treatment dynamic contrast-enhanced MRI using computer-aided detection is associated with response to neo-adjuvant chemotherapy.

PURPOSE: To evaluate whether enhancement of breast cancer on pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as evaluated semi-quantitatively using computer-aided detection (CAD) is associated with response to neo-adjuvant chemotherapy. MATERIALS AND METHODS: A total of 84 women, (mean age, 51±10 [SD] years; range: 30-73 years) with 84 breast cancers who underwent MRI before neo-adjuvant chemotherapy were included in this retrospective study. The proportion of each type of signal intensity-time curve (SITC) (type 1: persistent; type 2: plateau; Type 3: washout) within the tumor volume was quantified semi-automatically using a CAD system (Aegis®, Sentinelle medical, Toronto, Canada) and was compared to histological features of the tumors and to pathological response to neo-adjuvant chemotherapy. RESULTS: Pathological complete response was obtained in 29 patients (35%). Proportion of SITC type 1 was greater in non-responders (P=0.019) while proportion of SITC type 3 was greater in responders (P=0.04). Sensitivity, specificity, and accuracy of proportion of SITC type 1 for the identification of incomplete response on pathology were 42% (95% CI: 29%-56%), 90% (95% CI: 73%-98%), and 59% (95% CI: 48%-70%), respectively. CONCLUSION: Proportion of SITC type 1 (persistent) in breast cancers on pre-treatment MRI as semi-automatically quantified using a CAD system is associated with absence of pathological complete response to neo-adjuvant chemotherapy with good specificity.

Prediction of hemorrhagic transformation after acute thrombolysis following major artery occlusion using relative ADC ratio: A retrospective study.

BACKGROUND: The relative apparent diffusion coefficient (ADC) ratio can be used to evaluate the extent of ischemia. We investigated the risk factors for, and correlation between, relative ADC ratio and hemorrhagic transformation (HT) after thrombolysis. METHODS: This single-center, retrospective study involved 105 patients with acute occlusion of the anterior circulation. Relative ADC ratio was calculated as the ratio of ADC pixel values, within the affected territory to ADC pixel values in the contralateral normal region. HT was determined by computed tomography and T2* weighted magnetic resonance imaging after endovascular revascularization. RESULTS: Data for 80 of the 105 patients were analyzed. Comparing the number of patients between the HT group (n=25) and the non-HT group (n=55), a significant difference was noted in tissue plasminogen activator (tPA) use (P=0.028), time from onset to reperfusion ≥380min (P<0.001), fluid-attenuated inversion recovery (FLAIR) hyperintensity (P=0.009), and relative ADC ratio<0.650 (P<0.001). Multivariable logistic regression analysis identified relative ADC ratio<0.650 as the only independent predictor of HT (odds ratio 7.79; 95% confidence interval 2.22-27.3; P=0.001). Twenty-nine patients (including 20 in the HT group) had a relative ADC ratio<0.650. Multivariable logistic regression analysis identified use of tPA as the only independent predictor of HT (odds ratio 13.8; 95% confidence interval 1.35-125.5; P=0.010). CONCLUSIONS: Relative ADC ratio<0.650 with use of tPA may be important for predicting HT.

REPEATED INTRANODAL LYMPHANGIOGRAPHY FOR THE TREATMENT OF LYMPHATIC LEAKAGE.

Treatment of patients with chylous or non-chylous lymphatic leakage can be difficult. An approach using therapeutic lymphangiography can reduce the lymphatic leakage, but it seldom stops the leakage immediately and subsequent conservative treatment is necessary. We report three cases in which intranodal lymphangiography was performed multiple times to inhibit lymphatic leakage. In each case, the lymph node was punctured under ultrasound guidance using a 23-gauge needle and lipiodol was injected manually at a rate of 1 ml/3 min. The procedure was repeated twice in two cases of gastrointestinal carcinoma and four times in one case of lymphoma. In all three cases, the postoperative lymphatic leakage stopped after the repeated intranodal lymphangiography.

A hollow-fibre column system to effectively prepare washed platelets.

BACKGROUND AND OBJECTIVES: We developed a hollow-fibre column system specifically adapted to prepare washed platelet concentrates (WPCs). This study was performed to evaluate the efficacy of the hollow-fibre column system for preparing WPCs. MATERIALS AND METHODS: First, the percentages of platelet (PLT) recovery and remaining plasma proteins were calculated by determining the PLT count, volume and plasma protein levels in both the prewash and postwash. Secondly, washed PLTs and unwashed control PLTs were stored for 5 days, and the changes during this 5-day storage of in vitro PLT characteristics were determined. RESULTS: The hollow-fibre column system effectively removed >98% of plasma in platelet concentrates (PCs), and the PLT recovery was 97% on an average. The CD62P-expression level on washed PLTs immediately after washing was approximately twofold higher than that on prewashed PLTs as well as on PLTs washed via manual methods or cell washing devices. Until day 5 during storage, PLT aggregability, hypotonic shock response and swirling scores of washed PLTs were not significantly different from those of the control PCs. CONCLUSION: Our novel hollow-fibre column system proved valuable in preparing washed PLTs with <2% of residual plasma proteins and high recovery of PLTs.

Type 2 diabetes reduces the proliferation and survival of oligodendrocyte progenitor cells in ishchemic white matter lesions.

Diabetes mellitus (DM) is a major risk factor for stroke and it exacerbates tissue damage after ischemic insult. Diabetes is one of the important causes of the progression of white matter lesion, however, the pathological mechanisms remain unclear. The present study evaluated the influences of type 2 DM on ischemic subcortical white matter injury and the recruitment of oligodendrocyte progenitor cells (OPCs) under chronic cerebral hypoperfusion using type 2 diabetic (db/db) mice. After bilateral common carotid artery stenosis (BCAS), the rarefaction in the white matter was more severe in db/db mice than in db/+ mice, and the number of glutathione S-transferase-pi (GST-pi)-positive mature oligodendrocytes (OLG) was lower in db/db mice than in db/+ mice at 4 and 8 weeks after ischemia. There were no significant differences in the number of single-stranded DNA (ssDNA)-positive apoptotic cells in the deep white matter between the db/db and db/+ mice. We found a transient increase in the platelet-derived growth factor receptor-α (PDGFRα)-positive OPCs in white matter lesions after ischemia. However, significantly fewer PDGFRα-positive OPCs were detected in db/db than db/+ mice from 4weeks after BCAS. The number of Ki67-positive proliferating cells in the deep white matter was significantly lower in db/db mice than in db/+ mice from 4 to 8weeks after BCAS. Most of the Ki67-positive cells were PDGFRα-positive OPCs. Finally, we assessed the survival of 5-bromo-2'-deoxyuridine (BrdU)-positive proliferating cells in ischemic white matter, and found significantly poorer survival of BrdU/PDGFRα-positive OPCs or BrdU/GST-pi-positive OLGs in the db/db mice compared to the db/+ mice in the white matter after BCAS. Our findings suggest that the type 2 DM mice exhibited more severe white matter injury 8 weeks after chronic ischemia. Decreased proliferation and survival of OPCs may play an important role in the progression of white matter lesions after ischemia in diabetics.

Computed diffusion-weighted MRI for prostate cancer detection: the influence of the combinations of b-values.

OBJECTIVE: To evaluate the influence of the combinations of b-values on computed diffusion-weighted images (cDWIs) for prostate cancer (PCa) detection at b = 2000 s mm(-2). METHODS: Diffusion-weighted imaging (DWIs) for 31 patients with PCa (65.2 ± 7.1 years) were obtained pre-operatively at different b-values (0, 100, 500, 1000 and 2000 s mm(-2)) on a 3-T MRI. cDWIs at b = 2000 were generated by using six b-value combinations: 0-100 s mm(-2) (cDWI0-100); 0-500 s mm(-2) (cDWI0-500); 100-500 s mm(-2) (cDWI100-500); 0-1000 s mm(-2) (cDWI0-1000); 100-1000 s mm(-2) (cDWI100-1000); and 500-1000 s mm(-2) (cDWI500-1000). These cDWIs and measured DWIs with b = 2000 s mm(-2) (mDWI2000) were evaluated in this setting. To assess image quality for each DWI, contrast ratios (CRs) of cancerous and non-cancerous lesions were evaluated. To compare the detectability of PCa for each DWI, receiver operating characteristic analysis was used. RESULTS: CRs of all cDWIs were significantly higher than those of mDWI2000 (p < 0.05). Areas under the curve of cDWI0-100 (0.62) and cDWI0-500 (0.65) were significantly smaller (p < 0.05) than those of others (cDWI100-500, 0.72; cDWI0-1000, 0.73; cDWI100-1000, 0.71; cDWI500-1000, 0.74; mDWI2000, 0.72). CONCLUSION: The combinations of b-values influenced image quality and diagnostic ability of cDWIs for PCa detection. The combinations of b ≥ 100 and b ≥ 500 s mm(-2), as well as b = 0 and b = 1000 s mm(-2), were optimal in this study. ADVANCES IN KNOWLEDGE: For generating the useful cDWI for PCa detection, radiologists should take care of the combination of b-values when including low b-values.

The development of humanized liver with Rag1 knockout rats.

BACKGROUND: The animal model with humanized liver is useful for testing drug metabolism and toxicity in preclinical studies. A mouse model has been reported in which the liver was repopulated more than 90% with human hepatocytes; however, in the rat, the target is far from being reached. In this study, we attempt to develop a humanized liver model with an immunodeficient rat. METHODS: Rag1 knockout rats were treated with neonatal thymectomy. At 3 and 4 weeks of age, they were injected with hepatotoxin retrorsine; 2 weeks after, the animals were subjected to 70% partial hepatectomy and transplanted with immature human hepatocytes via portal vein. The recipients were also treated with anti-asialo GM1 antibody weekly from the day before transplantation and were injected with FK506 every 3 days after transplantation. RESULTS: In Rag1 knockout rats, B lymphocytes were deleted almost completely in peripheral blood. However, T and natural killer (NK) lymphocytes were kept present. When they were treated additionally with neonatal thymectomy for T-lymphocyte deletion and suppressed neutralized NK lymphocytes with anti-asialo GM1, B, T, and NK cells in lymphocytes were reduced to very low levels of 0.75%, 1.58%, and 0.26%, respectively. After transplanting human donor hepatocytes into retrorsine-treated recipient livers, at week 3 the human cell-derived hepatic colonies were expanded in the recipient liver and the liver repopulation rate with human hepatocytes reached approximately 17%. The human hepatocyte-specific genes, albumin, CYP3A4, CYP2C18, and CYP2C9, also could be detected in the recipient rat. CONCLUSION: It is possible to generate a chimera animal with humanized liver in a novel severely immunodeficient rat model.

Evidence of a sophisticatedly heterogeneous population of human umbilical vein endothelial cells.

Induction and promotion of angiogenesis play a role in a diverse range of physiologic and pathophysiologic processes that are especially relevant to the field of regenerative medicine. For assessing vasculogenesis and neo-angiogenesis, identifying angiogenic factors, angiocrine factors, and vascular niche, facilitating tissue-repair and tumor growth, efficiently generating induced pluripotent stem cells, and coculturing with organ-specific stem cells, isolation and characterization of the subpopulation of human umbilical vein endothelial cells (HUVECs) and their endothelial progenitor cells (EPCs) are needed. In this study, primary HUVECs were collected from fresh umbilical cords and fractionated and characterized with the use of flow cytometry. Clonal colony assay showed that endothelial colony-forming units in culture frequently existed in fresh HUVECs. Antigenic profiling demonstrated that undifferentiated EPCs in HUVECs had normal endothelial marker CD31 with a subpopulation of cells positive for hematopoietic stem cell marker CD34 and c-Kit. With continuing passages, EPC markers CD34 and vascular endothelial growth factor receptor 2 expression decreased dramatically. Moreover, a distinct subpopulation with different proliferative capability and angiogenesis from the early-passage HUVECs was shown. In conclusion, it is possible to isolate accurately and to enrich EPCs or hematoangioblast-like cells from a heterogeneous population of HUVECs, and to explore the differential process with flow cytometry for further investigations.

Evaluation of genetic introgression from domesticated pigs into the Ryukyu wild boar population on Iriomote Island in Japan.

We evaluated genetic introgression from domesticated pigs into the Ryukyu wild boar (RWB) population on Iriomote Island based on their genetic structure and diversity. We used a combination of mitochondrial DNA D-loop region (596 bp) polymorphisms and 23 microsatellite markers. RWBs (n = 130) were collected from 18 locations on Iriomote Island and compared with 66 reference samples of European and Asian domestic pigs. We identified six distinct haplotypes, involving 22 single nucleotide polymorphisms (including one insertion) in the RWB population. The phylogenetic tree had two branches: the RWB group and domestic lineage. Fourteen of 130 RWBs (10.8%) belonged to the European domestic lineage, including 11 RWBs from the Panari Islands, northwest of Iriomote Main Island (IMI). The heterozygosity values, total number of alleles, number of effective alleles and polymorphism information content of the RWB groups were lower than those of the European domestic groups. The RWB population on IMI had a lower heterozygous deficiency index (FIS = 0.059) than did the other populations, which indicates that this population was more inbred. There was a large genetic distance (FST = 0.560) between RWBs on IMI and the Meishan populations. Structure analysis using the 23 microsatellite markers revealed that 16 RWBs had an admixture pattern between RWB and domesticated pig breeds. These results suggest that gene flow may have occurred from domestic pigs to RWBs and demonstrate that there was low genetic variation in the IMI population.

Visceral fat accumulation is associated with cerebral small vessel disease.

BACKGROUND AND PURPOSE: Obesity is associated with the risk of coronary artery disease and stroke. Visceral fat plays a significant role in the atherogenic effects of obesity. Whether visceral fat accumulation, as measured by computed tomography (CT), is an independent risk factor for the presence of cerebral small vessel disease (SVD) was investigated. METHODS: This study comprised 506 Japanese subjects 35-74 years of age (mean 55.3 years) without a history of symptomatic cerebrovascular disease who underwent health screening tests, including brain magnetic resonance imaging, carotid echography and measurements of the visceral fat area (VFA) and subcutaneous fat area (SFA) on abdominal CT. Visceral fat accumulation was defined as VFA ≥ 100 cm(2) . Logistic regression analysis was performed to examine the associations between visceral fat accumulation and cerebral SVD such as white matter lesions (WMLs) and silent lacunar infarction (SLI). RESULTS: The prevalence of WMLs and SLI but not carotid plaque were significantly higher in subjects with VFA ≥ 100 cm(2) than those with VFA < 100 cm(2) . A VFA ≥ 100 cm(2) was associated with WMLs and SLI independent of age, cardiovascular risk factors and other measurements of obesity, such as waist circumference and body mass index. A large waist circumference was independently associated with SLI. SFA, the combination of VFA and SFA, and body mass index were not associated with WMLs or SLI. CONCLUSIONS: Visceral fat accumulation was independently associated with the presence of cerebral SVD in subjects without a history of symptomatic cerebrovascular disease.

Virulence genes and antimicrobial susceptibility in Pasteurella multocida isolates from calves.

A total of 378 isolates of Pasteurella multocida from clinically healthy and diseased calves were characterised for their susceptibility to 9 antimicrobial agents and screened by PCR for the presence of antimicrobial resistance genes and 22 genes virulence-associated, including capsule biosynthesis genes. Of the 378 isolates, 102 (27.0%) were resistant to at least one of the 9 tested antimicrobial agents. Resistance to oxytetracycline (21.7%) was the most frequently observed phenotype among the isolates. The tet(H) gene were the primary determinant detected. The resistance rates for thiamphenicol, ampicillin, kanamycin and florfenicol were 13.2%, 5.8%, 9.0% and 0.5%, respectively. Cefazolin, ceftiofur, cefquinome and enrofloxacin were effective antimicrobial agents, with no resistant isolates emerging over the course of the investigation. Most isolates were identified as capsular type A, only 6.3% belonged to capsular type D and no other capsular type was identified. Four of the virulence-associated genes (pfhA, tadD, tbpA and HAS) exhibited associations to the capsular type, and three (pfhA, tbpA and hgbB) were associated with the disease status of the animals. These virulence genes have been considered as epidemiological markers and are hypothesised to have a strong positive association with the outcome of disease in cattle.

Self-organization of human hepatic organoid by recapitulating organogenesis in vitro.

BACKGROUND: Careful orchestration among endodermal epithelial, endothelial, and mesenchymal cells initiate liver organogenesis prior to vascular function. Nonparenchymal endothelial or mesenchymal cells not only form passive conduits, but also establish an organogenic stimulus. Herein, we have evaluated the potential roles of primitive endothelial and mesenchymal cells toward hepatic organization in vitro. METHODS: To track the cellular movements and localization, we retrovirally transduced enhanced green fluorescence protein and kusabira orange into human fetal liver cells (GFP-hFLCs) and human umbilical vein endothelial cells (KO-HUVECs), respectively. GFP-hFLCs were cocultivated with KO-HUVECs and human mesenchymal stem cells (hMSCs) under conventional two-dimensional (2D) conditions. RESULTS: Even under 2D culture, fetal liver, endothelial, and mesenchymal cells self-organized into a macroscopically visible three-dimensional (3D) organoid. Time-lapse confocal imaging showed dynamic cellular organizations of GFP-hFLCs and KO-HUVECs. Endothelial cells organized into patterned clusters wrapping fetal liver cells, forming vessel-like lumens inside. Mesenchymal cells supported the generated organoid from outside. CONCLUSION: Generation of whole organ architecture remains a great challenge so far. Our preliminary results showed that recapitulation of primitive cellular interactions during organogenesis elicit the intrinsic self-organizing capacity to form hepatic organoids. Future studies to define precise conditions mimicking organogenesis may ultimately lead to the generation of a functional liver for transplantation and for other applications such as drug development.

Generation of functional human vascular network.

BACKGROUND: One of the major obstacles in regenerating thick, complex tissues such as the liver is their need for vascularization, which is essential to maintain cell viability during tissue growth and to induce structural organization. Herein, we have described a method to engineer a functional human vascular network. METHODS: Enhanced green fluorescence protein-labeled human umbilical vein endothelial cells (GFP-HUVECs) were cocultivated with kusabira orange-labeled human mesenchymal stem cells (KO-hMSCs) inside a collagen/fibronectin matrix. Premature vascular network formation was visualized by fluorescence microscopy imaging. Furthermore, constructs prevascularized in vitro were implanted into a transparency window in immunodeficient mice. RESULTS: Following several days of cultivation, GFP-HUVECs formed vessel-like structures that were stabilized by pericytes differentiated from KO-hMSCs. After implantation in vivo, the patency of human vascular structures was proved by rhodamine dextran infusion. These functional vascular structures remained for over 2 months. DISCUSSION: Vascularization is the key challenge to organ generation. We successfully generated human vascular networks inside a matrix. Integration of parenchymal cells using our engineering technique should facilitate future efforts to reconstitute vascularized human organ systems in vitro.

STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis.

In chronic myeloid leukemia (CML), the BCR-ABL fusion oncoprotein activates multiple pathways involved in cell survival, growth promotion and disease progression. In this report, we show that the signal-transducing adaptor protein-2 (STAP-2) is involved in BCR-ABL activity. We demonstrate that STAP-2 bound to BCR-ABL, and BCR and ABL proteins, depending on the STAP-2 Src homology 2-like domain. BCR-ABL phosphorylates STAP-2 Tyr250 and the phosphorylated STAP-2 in turn upregulated BCR-ABL phosphorylation, leading to enhanced activation of downstream signaling molecules including ERK (extracellular-signal-regulated kinase), STAT5 (signal transducer and activator of transcription 5), BCL-xL (B-cell lymphoma-extra large) and BCL-2(B-cell lymphoma 2). In addition, STAP-2 interacts with BCR-ABL to alter chemokine receptor expression leading to downregulation of CXCR4 and upregulation of CCR7. The interaction between STAP-2 and BCR-ABL plays a crucial role in conferring a growth advantage and resistance to imatinib, a BCR-ABL inhibitor, as well as tumor progression. Notably, mice injected with BCR-ABL/STAP-2-expressing Ba/F3 cells developed lymph node enlargement and hepatosplenomegaly. Moreover, suppression of STAP-2 in K562 CML cells resulted in no tumor formation in mice. Our results demonstrate a critical contribution of STAP-2 in BCR-ABL activity, and suggest that STAP-2 might be an important candidate for drug development for patients with CML. Furthermore, the expression of STAP-2 provides useful information for estimating the characteristics of individual CML clones.