External quality assessment-based tumor marker harmonization simulation; insights in achievable harmonization for CA 15-3 and CEA.

OBJECTIVES: CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples. METHODS: CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020-2021) and KEQAS (2020-2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%). RESULTS: Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from -29.28 to 9.86 %, into -0.09-0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from -23.78 to 2.00 % pre-harmonization to -3.13-1.42 % post-harmonization. CONCLUSIONS: The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs.

Investigating the Current Harmonization Status of Tumor Markers Using Global External Quality Assessment Programs: A Feasibility Study.

BACKGROUND: The harmonization status of most tumor markers (TMs) is unknown. We report a feasibility study performed to determine whether external quality assessment (EQA) programs can be used to obtain insights into the current harmonization status of the tumor markers α-fetoprotein (AFP), prostate specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, CA15-3 and CA19-9. METHODS: EQA sample results provided by 6 EQA providers (INSTAND [Germany], Korean Association of External Quality Assessment Service [KEQAS, South Korea], National Center for Clinical Laboratories [NCCL, China], United Kingdom National External Quality Assessment Service [UK NEQAS, United Kingdom], Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek [SKML, the Netherlands], and the Royal College of Pathologists of Australasia Quality Assurance Programs [RCPAQAP, Australia]) between 2020 and 2021 were used. The consensus means, calculated from the measurement procedures present in all EQA programs (Abbott Alinity, Beckman Coulter DxI, Roche Cobas, and Siemens Atellica), was used as reference values. Per measurement procedure, the relative difference between consensus mean for each EQA sample and the mean of all patient-pool-based EQA samples were calculated and compared to minimum, desirable, and optimal allowable bias criteria based on biological variation. RESULTS: Between 19040 (CA15-3) and 25398 (PSA) individual results and 56 (PSA) to 76 (AFP) unique EQA samples were included in the final analysis. The mean differences with the consensus mean of patient-pool-based EQA samples for all measurement procedures were within the optimum bias criterion for AFP, the desirable bias for PSA, and the minimum bias criterion for CEA. However, CEA results <8 µg/L exceeded the minimum bias criterion. For CA125, CA15-3, and CA19-9, the harmonization status was outside the minimum bias criterion, with systematic differences identified. CONCLUSIONS: This study provides relevant information about the current harmonization status of 6 tumor markers. A pilot harmonization investigation for CEA, CA125, CA15-3, and CA19-9 would be desirable.

Multicenter comparison of analytical interferences of 25-OH vitamin D immunoassay and mass spectrometry methods by endogenous interferents and cross-reactivity with 3-epi-25-OH-vitamin D3.

Background: Vitamin D (vit-D) deficiency is highly prevalent in the Korean population, highlighting the need for accurate measurements. In this study, the interferences by endogenous and cross-reactive substances were compared between routine vit-D immunoassays and mass spectrometry (MS) methods. Methods: Two MS methods and 4 immunoassays from different manufacturers (Abbott, Beckman Coulter, Roche, Siemens) were compared. Residual samples that were icteric, lipemic, hemolyzed, high in rheumatoid factor, from myeloma patients, or patients undergoing hemodialysis were collected. Also, 4 levels of National Institute of Standards and Technology (NIST) Standard Reference Material 972a, and 12 samples serially spiked with 3-epi-25-OH-D3 were prepared. Results: Significant interferences were observed in hemolytic (Roche), icteric (Beckman and Siemens) and lipemic samples (all 4 immunoassays). Level 4 NIST material and 3-epi-25-OH-D3-spiked samples induced significant cross-reactivity, yielding higher total vit-D measurements in non-epimer-separating MS methods, and both the Beckman and Roche immunoassays. Conclusion: Most observed interferences were consistent with manufacturers' claims, but overall improvement of immunoassay bias limits is required. Awareness of potential interference is important to increase the accuracy of vit-D measurements. Moreover, care is due when interpreting vit-D results of newborns, infants and less commonly, pregnant women, who are known to have physiologically high levels of the highly cross-reactive 3-epi-25-OH-D3.

A New Strategy for Evaluating the Quality of Laboratory Results for Big Data Research: Using External Quality Assessment Survey Data (2010-2020).

Background: To ensure valid results of big data research in the medical field, the input laboratory results need to be of high quality. We aimed to establish a strategy for evaluating the quality of laboratory results suitable for big data research. Methods: We used Korean Association of External Quality Assessment Service (KEQAS) data to retrospectively review multicenter data. Seven measurands were analyzed using commutable materials: HbA1c, creatinine (Cr), total cholesterol (TC), triglyceride (TG), alpha-fetoprotein (AFP), prostate-specific antigen (PSA), and cardiac troponin I (cTnI). These were classified into three groups based on their standardization or harmonization status. HbA1c, Cr, TC, TG, and AFP were analyzed with respect to peer group values. PSA and cTnI were analyzed in separate peer groups according to the calibrator type and manufacturer, respectively. The acceptance rate and absolute percentage bias at the medical decision level were calculated based on biological variation criteria. Results: The acceptance rate (22.5%-100%) varied greatly among the test items, and the mean percentage biases were 0.6%-5.6%, 1.0%-9.6%, and 1.6%-11.3% for all items that satisfied optimum, desirable, and minimum criteria, respectively. Conclusions: The acceptance rate of participants and their external quality assessment (EQA) results exhibited statistically significant differences according to the quality grade for each criterion. Even when they passed the EQA standards, the test results did not guarantee the quality requirements for big data. We suggest that the KEQAS classification can serve as a guide for building big data.

Clinical Performance of Two Automated Immunoassays, EliA CTD Screen and QUANTA Flash CTD Screen Plus, for Antinuclear Antibody Screening.

BACKGROUND: Recently, two fully automated immunoassays for antinuclear antibody (ANA) screening were introduced: EliA CTD Screen (Thermo Fisher Scientific, Freiburg, Germany) and QUANTA Flash CTD Screen Plus (Inova Diagnostics, San Diego, USA). We evaluated their clinical performance in comparison with the indirect immunofluorescence assay (IIFA) and analyzed samples with discrepant results. METHODS: In total, 406 serum samples (206 from patients undergoing routine checkups and 200 from rheumatology clinic patients) were assayed using EliA, QUANTA Flash, and IIFA. We evaluated assay concordance and agreement and confirmed the presence of anti-extractable nuclear antigen (ENA) antibodies in samples with discrepant automated immunoassay and IIFA results. Additionally, we compared the clinical performance of each assay in diagnosing ANA-associated rheumatic disease (AARD) and adjusted the cut-off values. RESULTS: In rheumatology clinic samples, the concordance and agreement were 91.5% and strong between EliA and QUANTA Flash, 79.0% and weak between EliA and IIFA, and 80.5% and moderate between QUANTA Flash and IIFA, respectively. In automated immunoassay-positive, IIFA-negative samples (N=15), all anti-ENA antibodies detected (6/15) were anti-Sjögren's syndrome antigen A/Ro (Ro60) antibodies. The automated immunoassays and IIFA showed high accuracy for diagnosing AARD, and adjusted cut-off values improved their sensitivities (EliA with 0.56 ratio, 82.9% sensitivity; QUANTA Flash with 9.7 chemiluminescent units, 87.8% sensitivity). CONCLUSIONS: The two automated immunoassays showed reliable performance compared with IIFA and can be efficiently used with the IIFA in clinical immunology laboratories. Clinical cut-off values can be adjusted according to the workflow in each laboratory.

Performance evaluation of coaguchek pro II in comparison with coaguchek XS plus and sta-r Max using a sta-neoplastine CI plus.

INTRODUCTION: We evaluated the analytical performance of CoaguChek Pro II (Roche Diagnostics GmbH, Mannheim, Germany), a new point-of-care device measuring the international normalized ratio (INR) values, in comparison with CoaguChek XS Plus (Roche Diagnostics GmbH) and STA-R Max using STA-Neoplastine CI Plus (Diagnostica Stago SAS, Asnières-sur-Seine, France). METHODS: The precision of Pro II was analyzed, according to the Clinical and Laboratory Standards Institute guidelines (CLSI POCT14-A2 and EP15-A3). In 105 clinical samples, the Pro II INR values were compared with those of XS Plus and STA-R Max using STA-Neoplastine CI Plus (CLSI EP09-A3 and EP35). We also compared the Pro II INR values between capillary blood (CB) and venous blood (VB; CLSI EP35). RESULTS: The precision of Pro II was acceptable (within-run and between-run CV%: 2.71% and 3.28% at normal level; 1.52% and 4.47% at abnormal level, respectively). The Pro II INR values showed very high correlation and almost perfect agreement with those of XS Plus and STA-R Max using STA-Neoplastine CI Plus (r = .97 and κ = .94; r = .95 and κ = .91). The mean difference between Pro II and STA-R Max using STA-Neoplastine CI Plus increased as INR values increased, with 60% of samples showing differences >0.5 in the supratherapeutic range. The Pro II INR values showed very high correlation between CB and VB (r = .98). CONCLUSION: Pro II INR values are accurate and reliable using both CB and VB; however, they should be confirmed by laboratory analyzers in the supratherapeutic range.

Effectiveness of Plasma and Urine Neutrophil Gelatinase-Associated Lipocalin for Predicting Acute Kidney Injury in High-Risk Patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for acute kidney injury (AKI) prediction. However, studies on whether using both plasma NGAL (PNGAL) and urine NGAL (UNGAL) can improve AKI prediction are limited. We investigated the best approach to predict AKI in high-risk patients when using PNGAL and UNGAL together. METHODS: We enrolled 151 AKI suspected patients with one or more AKI risk factors. We assessed the diagnostic performance of PNGAL and UNGAL for predicting AKI according to chronic kidney disease (CKD) status by determining the areas under the receiver operating curve (AuROC). Independent predictors of AKI were assessed using univariate and multivariate logistic regression analyses. RESULTS: In the multivariate logistic regression analysis for all patients (N=151), Model 2 and 3, including PNGAL (P=0.012) with initial serum creatinine (S-Cr), showed a better AKI prediction power (R2=0.435, both) than Model 0, including S-Cr only (R2=0.390). In the non-CKD group (N=135), the AuROC of PNGAL for AKI prediction was larger than that of UNGAL (0.79 vs 0.66, P=0.010), whereas in the CKD group (N=16), the opposite was true (0.94 vs 0.76, P=0.049). CONCLUSIONS: PNGAL may serve as a useful biomarker for AKI prediction in high-risk patients. However, UNGAL predicted AKI better than PNGAL in CKD patients. Our findings provide guidance for selecting appropriate specimens for NGAL testing according to the presence of CKD in AKI high-risk patients.

Combination Therapy by Tissue-Specific Suicide Gene and Bevacizumab in Intramedullary Spinal Cord Tumor.

PURPOSE: Malignant gliomas are aggressive spinal cord tumors. In this study, we hypothesized that combination therapy using an anti-angiogenic agent, bevacizumab, and hypoxia-inducible glioblastoma-specific suicide gene could reduce tumor growth. MATERIALS AND METHODS: In the present study, we evaluated the effect of combination therapy using bevacizumab and pEpo-NI2-SV-TK in reducing the proliferation of C6 cells and tumor growth in the spinal cord. Spinal cord tumor was generated by the injection of C6 cells into the T5 level of the spinal cord. Complexes of branched polyethylenimine (bPEI)/pEpo-NI2-SV-TK were injected into the spinal cord tumor. Bevacizumab was then administered by an intraperitoneal injection at a dose of 7 mg/kg. The anti-cancer effects of combination therapy were analyzed by histological analyses and magnetic resonance imaging (MRI). The Basso, Beattie and Bresnahan scale scores for all of the treatment groups were recorded every other day for 15 days to assess the rat hind-limb strength. RESULTS: The complexes of bPEI/pEpo-NI2-SV-TK inhibited the viability of C6 cells in the hypoxia condition at 5 days after treatment with ganciclovir. Bevacizumab was decreased in the cell viability of human umbilical vein endothelial cells. Combination therapy reduced the tumor size by histological analyses and MRI. The combination therapy group showed improved hind-limb function compared to the other groups that were administered pEpo-NI2-SV-TK alone or bevacizumab alone. CONCLUSION: This study suggests that combination therapy using bevacizumab with the pEpo-NI2-SV-TK therapeutic gene could be useful for increasing its therapeutic benefits for intramedullary spinal cord tumors.

Feasibility of the Epiduroscopy Simulator as a Training Tool: A Pilot Study.

Epiduroscopy is a type of spinal intervention that visualizes the epidural space through the sacral hiatus using a fiberoptic scope. However, it is technically difficult to perform compared to conventional interventions and susceptible to complications. Surgery simulator has been shown to be a promising modality for medical education. To develop the epiduroscopy simulator and prove its usefulness for epiduroscopy training, we performed a case-control study including a total of 20 physicians. The participants were classified as the expert group with more than 30 epiduroscopy experiences and the beginner group with less experience. A virtual simulator (EpiduroSIM™, BioComputing Lab, KOREATECH, Cheonan, Republic of Korea) for epiduroscopy was developed by the authors. The performance of the participants was measured by three items: time to reach a virtual target, training score, and number of times the dura and nerve are violated. The training score was better in the expert group (75.00 vs. 67.50; P < 0.01). The number of violations was lower in the expert group (3.50 vs. 4.0; P < 0.01). The realism of the epidural simulator was evaluated to be acceptable in 40%. Participants improved their simulator skills through repeated attempts. The epiduroscopy simulator helped participants understand the anatomical structure and actual epiduroscopy.

CRISPR/Cas9-Mediated Gene Correction to Understand ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the death of motor neurons in the spinal cord and brainstem. ALS has a diverse genetic origin; at least 20 genes have been shown to be related to ALS. Most familial and sporadic cases of ALS are caused by variants of the SOD1, C9orf72, FUS, and TARDBP genes. Genome editing using clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9 (CRISPR/Cas9) can provide insights into the underlying genetics and pathophysiology of ALS. By correcting common mutations associated with ALS in animal models and patient-derived induced pluripotent stem cells (iPSCs), CRISPR/Cas9 has been used to verify the effects of ALS-associated mutations and observe phenotype differences between patient-derived and gene-corrected iPSCs. This technology has also been used to create mutations to investigate the pathophysiology of ALS. Here, we review recent studies that have used CRISPR/Cas9 to understand the genetic underpinnings of ALS.

Combined Method of Neuronal Cell-Inducible Vector and Valproic Acid for Enhanced Gene Expression under Hypoxic Conditions.

BACKGROUND: Gene therapy shows the ability to restore neuronal dysfunction via therapeutic gene expression. The efficiency of gene expression and delivery to hypoxic injury sites is important for successful gene therapy. Therefore, we established a gene/stem cell therapy system using neuron-specific enolase promoter and induced neural stem cells in combination with valproic acid to increase therapeutic gene expression in hypoxic spinal cord injury. METHODS: To examine the effect of combined method on enhancing gene expression, we compared neuronal cell-inducible luciferase levels under normoxia or hypoxia conditions in induced neural stem cells with valproic acid. Therapeutic gene, vascular endothelial growth factor, expression with combined method was investigated in hypoxic spinal cord injury model. We verified gene expression levels and the effect of different methods of valproic acid administration in vivo. RESULTS: The results showed that neuron-specific enolase promoter enhanced gene expression levels in induced neural stem cells compared to Simian Virus 40 promoter under hypoxic conditions. Valproic acid treatment showed higher gene expression of neuron-specific enolase promoter than without treatment. In addition, gene expression levels and cell viability were different depending on the various concentration of valproic acid. The gene expression levels were increased significantly when valproic acid was directly injected with induced neural stem cells in vivo. CONCLUSION: In this study, we demonstrated that the combination of neuron-specific enolase promoter and valproic acid induced gene overexpression in induced neural stem cells under hypoxic conditions and also in spinal cord injury depending on valproic acid administration in vivo. Combination of valproic acid and neuron-specific enolase promoter in induced neural stem cells could be an effective gene therapy system for hypoxic spinal cord injury.

CRISPR-mediated gene correction links the ATP7A M1311V mutations with amyotrophic lateral sclerosis pathogenesis in one individual.

Amyotrophic lateral sclerosis (ALS) is a severe disease causing motor neuron death, but a complete cure has not been developed and related genes have not been defined in more than 80% of cases. Here we compared whole genome sequencing results from a male ALS patient and his healthy parents to identify relevant variants, and chose one variant in the X-linked ATP7A gene, M1311V, as a strong disease-linked candidate after profound examination. Although this variant is not rare in the Ashkenazi Jewish population according to results in the genome aggregation database (gnomAD), CRISPR-mediated gene correction of this mutation in patient-derived and re-differentiated motor neurons drastically rescued neuronal activities and functions. These results suggest that the ATP7A M1311V mutation has a potential responsibility for ALS in this patient and might be a potential therapeutic target, revealed here by a personalized medicine strategy.

An Epiduroscopy Simulator Based on a Serious Game for Spatial Cognitive Training (EpiduroSIM): User-Centered Design Approach.

BACKGROUND: Performing high-level surgeries with endoscopy is challenging, and hence, an efficient surgical training method or system is required. Serious game-based simulators can provide a trainee-centered educational environment unlike traditional teacher-centered education environments since serious games provide a high level of interaction (feedback that induces learning). OBJECTIVE: This study aimed to propose an epiduroscopy simulator, EpiduroSIM, based on a serious game for spatial cognitive training. METHODS: EpiduroSIM was designed based on a serious game. For spatial cognitive training, the virtual environment of EpiduroSIM was modeled based on a cognitive map. RESULTS: EpiduroSIM was developed considering user accessibility to provide various functions. The experiment for the validation of EpiduroSIM focused on psychological fidelity and repetitive training effects. The experiments were conducted by dividing 16 specialists into 2 groups of 8 surgeons. The group was divided into beginner and expert based on their epiduroscopy experience. The psychological fidelity of EpiduroSIM was confirmed through the training results of the expert group rather than the beginner group. In addition, the repetitive training effect of EpiduroSIM was confirmed by improving the training results in the beginner group. CONCLUSIONS: EpiduroSIM may be useful for training beginner surgeons in epiduroscopy.

Feasibility of Percutaneous Robot-Assisted Epiduroscopic System.

BACKGROUND: Endoscopy has replaced open surgery, especially in spinal surgery. Among them, image-guided epiduroscopy allows pain generators to be identified, including epidural adhesion, fibrotic tissues, root compression, and spinal stenosis. However, the heavy lead apron worn by pain physicians to avoid exposure to radiation can induce occupational hazards, such as orthopedic complications and radiation-induced cancer. Hence, we developed a robotic system to address these problems. OBJECTIVE: The aim of the study was to evaluate the feasibility of a robot-controlled epiduroscopic system. STUDY DESIGN: In vivo animal experiment. SETTING: University in Republic of Korea. METHODS: The robot-controlled epiduroscopic system was developed using the open architecture robot system (The Raven Surgical Robotic System, CITRIS, Berkley, CA, USA). The robotic system consists of a lab-made epiduroscope, steering section, robotic arm, and manipulator. For the in vivo study, 2 Yorkshire pigs were used to simulate an epiduroscopic procedure with the robotic system. RESULTS: The insertion and steering of the catheter was performed safely, and epiduroscopic visualization was obtained without side effects. There were no device-related complications. Radiation exposure for the primary operator was 80% lower than the levels found during conventional epiduroscopic procedures. All live pigs showed normal behavior without any signs of pain. The mean time to reach the target region was less than 8 minutes. LIMITATIONS: The epiduroscopic procedure was performed on pigs and not on humans. The dimensions of the spinal canal of pigs cannot compare to those of humans. CONCLUSIONS: We demonstrated the feasibility of the robot-assisted epiduroscopic system. KEY WORDS: Epiduroscopy, robotic system, spine, pig, animal model.

Multi-marker approach using procalcitonin, presepsin, galectin-3, and soluble suppression of tumorigenicity 2 for the prediction of mortality in sepsis.

BACKGROUND: Biomarker could be objective and reliable tools to predict mortality in sepsis. We explored the prognostic utilities of emerging biomarkers in septic patients and questioned whether adding biomarkers to the clinical variables would improve the prediction of mortality in sepsis. METHODS: This retrospective study included 157 septic patients (112 patients with sepsis; 45 patients with septic shock). Procalcitonin (PCT), presepsin, galectin-3, and soluble suppression of tumorigenicity 2 (sST2) concentrations were analyzed in relation to the 30-day all-cause mortality. Their value added on top of Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score, high-sensitivity C-reactive protein, and white blood cells was also analyzed. RESULTS: PCT could not predict 30-day mortality. Univariate hazard ratio [HR with 95% confidence interval (CI)] of the other dichotomized variables was: 1.33 (0.55-3.194) for presepsin; 7.87 (2.29-26.96) for galectin-3; 1.55 (0.71-3.38) for sST2; and 2.18 (1.01-4.75) for SOFA score. The risk of 30-day mortality increased stepwise as the number of biomarkers above optimal cutoff values increased, and the highest risk was observed when all four biomarkers and SOFA score increased (HR = 14.5). Multi-marker approach predicted 30-day mortality better than SOFA score [area under the curves (95% CI), 0.769 (0.695-0.833) vs. 0.615 (0.535-0.692)]. In reclassification analyses, adding biomarkers to clinical variables improved the prediction of mortality. CONCLUSION: This study demonstrated a possible prognostic utility of PCT, presepsin, galectin-3, and sST2 in sepsis. Multi-marker approach could be beneficial for an optimized management of patients with sepsis.

Discovery of gastric cancer specific biomarkers by the application of serum proteomics.

Current diagnostic markers for gastric cancer are not sufficiently specific or sensitive for use in clinical practice. The aims of this study are to compare the proteomes of serum samples from patients with gastric cancers and normal controls, and to develop useful tumor markers of gastric cancer by quantitative proteomic analysis. We identified a total of 388 proteins with a ≤1% FDR and with at least two unique peptides from the sera of each group. Among them, 215, 251, and 260 proteins were identified in serum samples of patients in an advanced cancer group, early cancer group, and normal control group, respectively. We selected differentially expressed proteins in cancer patients compared with those of normal controls via semiquantitative analyses comparing the spectral counts of identified proteins. These differentially expressed proteins were successfully verified using an MS-based quantitative assay, multiple reactions monitoring analysis. Four proteins (vitronectin, clusterin isoform 1, thrombospondin 1, and tyrosine-protein kinase SRMS) were shown to have significant changes between the cancer groups and the normal control group. These four serum proteins were able to discriminate gastric cancer patients from normal controls with sufficient specificity and selectivity.

First Case of Biphenotypic/bilineal (B/myeloid, B/monocytic) Mixed Phenotype Acute Leukemia with t(9;22)(q34;q11.2);BCR-ABL1.

Mixed phenotype acute leukemia (MPAL) includes biphenotypic leukemia, bilineal leukemia, or its combination by the 2008 WHO classification. A few cases of combined biphenotypic/bilineal MPAL have been reported so far; they all had biphenotypic expressions in only one of the two distinct leukemic populations. A 43-year-old female presented with leukocytosis and bicytopenia. Her complete blood counts were: hemoglobin, 6.9 g/dL; white blood cells, 62.8×10(9)/L; and platelets, 83×10(9)/L. Neither lymphadenopathy nor organomegaly was observed. Blasts and promonocytes/monoblasts were increased in her peripheral blood (42%) and bone marrow (60.1%). Flow cytometric analysis revealed two distinct populations of leukemic cells, which expressed CD11c, CD19, and cytoplasmic CD79a in common. Additionally, the first population expressed CD10 and CD117 (B/myeloid), and the second one expressed CD14 and CD20 (B/monocytic). She had a karyotype of 46,XX,inv(9)(p12q13),t(9;22)(q34;q11.2)[20] and BCR/ABL1 rearrangement. To the best of our knowledge, this is the first reported case of biphenotypic/bilineal MPAL with B/myeloid and B/monocytic expressions.