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The origin and propagation of normal and leukemic hematopoietic cells critically depend on their interplays with the hematopoietic microenvironment (or so-called niche), which represent important biological models for understanding organogenesis and tumorigenesis. Nevertheless, the anatomic and functional characterizations of the niche cells for normal hematopoietic stem cells (HSCs) have proved a formidable task. It is uncertain whether the combinational effects of a few sets of molecular niche elements, behind the long-sought cellular architectures with preferred anatomic locations, actually meets the functional definition of HSC niche. Moreover, even much less is known about the niche components for numerous types of leukemia-stem cells (LSCs) that originate via discrete cellular and molecular transforming mechanisms. However, one interesting scenario is emerging, i.e., the leukemia cells can positively remodel the hematopoietic microenvironment favorable for their competition over the normal hematopoiesis that co-exists within the same eco-system. This property probably represents a previously unappreciated essential trait of a functional LSC. Obviously, the further exploration into how the hematopoietic microenvironment interplay with normal or malignant hematopoiesis will shed light onto the designing of novel types of niche-targeting therapies for leukemia. [ABSTRACT FROM AUTHOR]

In this paper, two effective fuzzy control schemes, i.e., fuzzy feedback control method and adaptive fuzzy control method are introduced to suppress the state variables of the Lorenz-Stenflo chaotic system (LSCS) to its equilibrium point. For the first fuzzy control scheme, with the abundant modeling capability of the T-S fuzzy model, the LSCS can be decomposed into some local linear systems, which makes it very convenient to use the fuzzy feedback control method to analyze it. Based on the Lyapunov stability theorem, a criterion is also derived to guarantee the controlled LSCS is robust stable at the equilibrium point, even if there exist external perturbations. For the second fuzzy control scheme, fuzzy logic systems areexploited to approximate the nonlinear functions. Moreover, an adaptive technique is employed to construct an effective fuzzy controller, which can drive all state variables into a rather small neighborhood of its equilibrium point. By choosing a group of suitable parameters, the controlled system can approach the equilibrium point with high precision. Two numerical simulations are presented to demonstrate the effectiveness and feasibility of the two fuzzy control schemes. [ABSTRACT FROM PUBLISHER]

Identifying leukemia stem cells (LSCs) is a challenge and a critical step in understanding their respective biology and may provide insights into a more efficient treatment of acute lymphoblastic leukemia (ALL). This cohort study aimed at detecting LSCs expressing CD19, CD34, and CD38 in the bone marrow of 20 de novo Egyptian pediatric B-ALL patients at the time of the diagnosis and after the induction of chemotherapy. LSCs were detected in 80% of cases at the time of diagnosis and in 70% of the cases after the induction of chemotherapy. Patients were followed up for 12-18 months. No statistically significance difference was encountered between LSC-positive and LSC-negative patients as regards their clinical and laboratory data at the time of diagnosis. Furthermore, there was no statistically significant difference between the percentages of LSC-positive patients before or after induction of therapy. On follow-up, two patients died; they had residual LSCs after the induction therapy. However, the existence of LSCs did not affect the patient's 1-year disease-free survival rate. LSC may resist the traditional lines of treatment applied for childhood B-ALL; it may be used in minimal residual disease monitoring as well as being a target for new therapeutic lines to improve the outcome of treatment especially in patients with high-risk and relapsed ALL. [ABSTRACT FROM AUTHOR]

It has been proposed that iron-sulfur [Fe-S] clusters destined for the maturation of [Fe-S] proteins can be preassembled on a molecular scaffold designated IscU. In the present article, it is shown that production of the intact Azotobacter vinelandii [Fe-S] cluster biosynthetic machinery at levels exceeding the amount required for cellular maturation of [Fe-S] proteins results in the accumulation of: (i) apo-IscU, (ii) an oxygen-labile [2Fe-25] cluster-loaded form of IscU, and (iii) IscU complexed with the S-delivery protein, IscS. It is suggested that these species represent different stages of the [Fe-SI cluster assembly process. Substitution of the IscU Asp39 residue by Ala results in the in vivo trapping of a stoichiometric, noncovalent, nondissociating IscU-IscS complex that contains an oxygen-resistant [Fe-S] species. In aggregate, these results validate the scaffold hypothesis for [Fe-S] cluster assembly and indicate that in viva [Fe-S] cluster formation is a dynamic process that involves the reversible interaction of IscU and IscS. [ABSTRACT FROM AUTHOR]

We describe InterPlay, a simulation engine coordinator that supports cooperation and interaction of multiple simulation and execution tools, thus helping to scale up the design and development cycle of reactive systems. InterPlay involves a number of related ideas. In the first, we concentrate on the interobject design approach involving live sequence charts (LSCs) and its support tool, the Play-Engine, enabling multiple Play-Engines to run in cooperation. This makes possible the distributed design of large-scale systems by different teams, as well as the refinement of parts of a system using different Play-Engines. The second idea concerns combining the interobject approach with the more conventional intraobject approach, involving, for example, state-charts and Rhapsody. InterPlay makes it possible to run the Play-Engine in cooperation with Rhapsody, and is very useful when some system objects have clear and distinct internal behavior, or in an iterative development process where the design is implementation-oriented and the ultimate goal is to end up with an intraobject implementation. Finally, we have expanded the Play-Engine's ability to delegate some of the system's functionality to complex GUIs. This enables beneficial interaction with "smart" GUIs that have built-in behavior of their own, and which are more naturally implemented in code. [ABSTRACT FROM AUTHOR]

Simple Summary: CD26/dipeptidylpeptidase IV (DPP-4) is a membrane-bound multifunctional protein expressed in many primary solid tumors and in hematological diseases. Recent investigations demonstrated its specific expression on leukemic stem cells (LSCs) of Chronic Myeloid Leukemia (CML) bone marrow (BM) and peripheral blood (PB) samples. Thanks to this evidence, CD26 has been considered a novel exclusive stem cell marker of CML. The aim of this review is to describe and analyze the role of CD26 in the context of hematological malignancies and specifically of CML and to highlight its potential clinical application for the management of this disease. CD26 expression is altered in many solid tumors and hematological malignancies. Recently, it has been demonstrated that it is a specific marker expressed on LSCs of CML, both in BM and PB samples, and absent on CD34+/CD38− stem cells in normal subjects or on LSCs of other myeloid neoplasms. CD26+ LSCs have been detected by flow-cytometry assays in all PB samples of Chronic-Phase CML patients evaluated at diagnosis. Additionally, it has been demonstrated that most CML patients undergoing Tyrosine Kinase Inhibitors (TKIs) treatment still harbored circulating measurable residual CD26+ LSCs, even when displaying a consistent deep molecular response without any significant association among the amounts of BCR-ABL transcript and CD26+ LSCs. Preliminary data of our Italian prospective multicenter study showed that CML patients with a poorer response presented with a higher number of CD26+ LSCs at diagnosis. These data confirmed that CD26 is a specific marker of CML and suggest that it could be considered for the monitoring of therapeutic responses. [ABSTRACT FROM AUTHOR]

Rupture of gravid uterus with its sequelae remains one of the most disastrous complications of pregnancy occurring invariably at or near term. Uterine rupture is an obstetric catastrophe that is associated with high rates of maternal and perinatal mortality!. In India it still accounts for 5-10% of all maternal deaths2. Besides the unscarred uterine rupture, the developing countries are now having increased incidence of scarred uterine rupture due to rising rate of caesarean section-a new problem to be addressed3. One such case of a pregnant woman was brought dead to casualty of Sri Aurobindo Medical College and PG Institute. Post Mortem Examination revealed that it was a case of rupture uterus with the history of previous LSCS 1 year back. Proper antenatal examination and care might have avoided the mishap. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease most frequently found in women of child bearing age and may co-exist with pregnancy. Disease exacerbation, increased foetal loss, neonatal lupus and an increased incidence of pre-eclampsia are the major challenges. Its multisystem involvement and therapeutic interventions like anticoagulants, steroids and immunosuppressive agents pose a high risk for both surgery and anaesthesia. We describe successful management of an antinuclear antibody (ANA) positive parturient with bad obstetric history who underwent elective caesarean section under spinal anaesthesia. [ABSTRACT FROM AUTHOR]

Caesarean section involves the delivery of the fetus through a direct incision in the abdominal wall and the uterus. Women with scarred uterus are considered at risk of uterine rupture during subsequent pregnancies and labour. Although trial of labour is usually given to patients having past history of previous one lower segment caesarean section (LSCS) due to non recurrent cause with a considerable success rate but most obstetricians opt an elective LSCS in women having past history of two or more LSCS. We report a case of three consecutive successful vaginal deliveries with an intact scar in a woman having history of previous 3 LSCS [ABSTRACT FROM AUTHOR]

Objective: To find out the effect of increasing body mass index (BMI) on pregnancy outcomes in nulliparous women delivering singleton babies. Method: This was a hospital-based observation study, based on 300 nulliparous women delivering singleton babies in June 2009-Sept. 2010. Women were categorized into three groups. Underweight (BMI < 20 kg/m), normal (BMI 20-24.9 kg/m), overweight (BMI 25-29.9 kg/m), and obese (BMI > 30 kg/m) obstetric and perinatal outcomes were compared by univariate and multivariate analysis. Results: Maximum patients who underwent LSCS were having BMI > 30 kg/m [OR 9.558 (95 % CI 5.82-17.27)]. As compared to women of normal BMI (20-24.9 kg/m), morbidly obese women faced the higher risk of PIH [OR 8.045 (95 % CI 3.875-16.781)]. Obese women were more likely to have post partum hemorrhage [OR 5.11 (95 % CI 1.76-14.79)] compared with women of normal BMI. Birth weight <2,500 g was more common in women with BMI < 25 kg/m (21.21 %), while highest incidence of birth weight >4,000 g (14.29 %) is seen in women of the obese group. Conclusions: Increasing BMI is associated with increased incidence of cesarean delivery, PIH, post partum hemorrhage, and macrosomic babies. [ABSTRACT FROM AUTHOR]

A case report of a primigravida, who was admitted with severe pregnancy induced hypertension (BP 160/122 mmHg) and twin pregnancy, is presented here. Antihypertensive therapy was initiated. Elective LSCS under general anaesthesia was planned. After the birth of both the babies, intramyometrial injections of Carboprost and Pitocin were administered. Immediately, she suffered cardiac arrest. Cardio pulmonary resucitation (CPR) was started and within 3 minutes, she was successfully resuscitated. The patient initially showed peculiar psychological changes and with passage of time, certain psycho-behavioural patterns emerged which could be attributed to near death experiences, as described in this case report. [ABSTRACT FROM AUTHOR]

This study aimed to address the prognostic relevance of CD34 + /CD38 - /TIM3 + leukemic stem cell (LSC) frequency in patients with acute myeloid leukemia (AML) and its impact on patient outcome. We analyzed the expression of LSC markers (CD34 + /CD38 - /TIM3 + ) using flow cytometry in bone marrow samples of 53 AML cases before and after induction chemotherapy. The LSC frequency at diagnosis was significantly higher compared with that postinduction (P < .001). Patients were categorized into high LSC expressers (≥ median) and low expressers (< median). Patients with AML with high number of LSCs at diagnosis had significantly lower induction of remission response (P = .0104), shorter disease-free survival, and shorter overall survival (P < .001 for both) compared with those with lower LSC count. Cox regression analysis revealed that LSC frequency at diagnosis is an independent prognostic factor in AML. Assessment of LSCs (CD34 + /CD38 - /TIM3 + ) at diagnosis is recommended for refining of AML risk stratification., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Leukemic stem cells (LSCs) rely on oxidative metabolism and are differentially sensitive to targeting mitochondrial pathways, which spares normal hematopoietic cells. A subset of mitochondrial proteins is folded in the intermembrane space via the mitochondrial intermembrane assembly (MIA) pathway. We found increased mRNA expression of MIA pathway substrates in acute myeloid leukemia (AML) stem cells. Therefore, we evaluated the effects of inhibiting this pathway in AML. Genetic and chemical inhibition of ALR reduces AML growth and viability, disrupts LSC self-renewal, and induces their differentiation. ALR inhibition preferentially decreases its substrate COX17, a mitochondrial copper chaperone, and knockdown of COX17 phenocopies ALR loss. Inhibiting ALR and COX17 increases mitochondrial copper levels which in turn inhibit S-adenosylhomocysteine hydrolase (SAHH) and lower levels of S-adenosylmethionine (SAM), DNA methylation, and chromatin accessibility to lower LSC viability. These results provide insight into mechanisms through which mitochondrial copper controls epigenetic status and viability of LSCs., Competing Interests: Declaration of Interests A.D.S. has received honoraria or consulting fees from Novartis, Jazz, Otsuka, and Takeda Pharmaceuticals and research support from Medivir AB and Takeda. A.D.S. owns stock in Abbvie Pharmaceuticals and is named on a patent application for the use of DNT cells for the treatment of leukemia. D.V.J is currently an employee of Celgene/Bristol-Myers Squibb (BMS). M.D.M. has received consulting fees from Astellas, Abbvie, Celgene/BMS, and GlaxoSmithKline (GSK). S.M.C. has received honoraria from Celgene and Agios. S.M.C. has received research funding from Agios, Celgene, and Abbvie Pharmaceuticals., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Acute myeloid leukemia (AML) evolves from neoplastic transformation of stem cell disease termed "leukemia stem cells" (LSCs). An unsatisfactory response to AML therapy is determined by the presence of minimal residual disease (MRD). The predominance of LSCs might anticipate sustained MRD results. The present study aimed to demonstrate the effect of LSCs on MRD at induction days 14 and 28 on overall survival (OS) and disease-free survival (DFS) and to compare LSC expression with MRD status., Patients and Methods: A total of 84 patients with de novo adult AML underwent testing using LSC panels for CD38/CD123/CD34/CD45 and CD90/CD133/CD45/CD33 and different regular MRD panels., Results: At day 14 after induction, the high expression of CD123 and CD133 had adverse effects on both OS and DFS (P = .004 and P ≤ .001 and P ≤ .001 and P ≤ .001, respectively). Greater expression of CD34 + /CD38 - /CD123 + resulted in unfavorable OS and DFS (P ≤ .001 for both). Both CD34 + /CD38 - /CD123 + and CD34 - /CD38 + /CD123 + expression at day 14 after induction had an adverse effect on DFS only (P < .001 and P = .029, respectively). On multivariate analysis, CD133 expression and MRD status were independent prognostic parameters (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2-4.4; P = .015; and HR, 2.9; 95% CI, 1.0-7.9; P = .041). At day 28 after induction, MRD and increased CD123 + /CD34 - , CD34 + /CD38 - /CD123 + , CD133 + /CD33 - expression were associated with inferior OS (P = .016, P = .0035, P = .0.002, and P = .002, respectively). MRD and high expression of CD34 + CD123 + , CD133 + /CD33 - , CD34 + /CD38 - /CD123 + were associated with inferior DFS (P < .001, P = .002, P < .001, P < .001, respectively). On multivariate analysis, only CD133 + /CD33 - expression was the independent prognostic factor (HR, 3.1; 95% CI, 1.5-6.7; P = .003)., Conclusions: Estimation of LSC expression is a sensitive indicator of the response to therapy in adult patients with AML and might be a better prognosticator than the findings from regular MRD panels., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Acute myeloid leukemia (AML) is initiated and maintained by a unique, small subset of leukemia stem cells (LSCs). LSCs are characterized by unrestricted self-renewal and contribute to the malignancy of leukemia. Aberrant protein fucosylation is associated with AML progression. However, it is still less understood that the miR-29b/Sp1/FUT4 crosstalk involved in the fucosylation-mediated LSCs malignancy in AML. Methods: AML cell lines were sorted by magnetic microbeads to obtain the CD34 + CD38- sub-population. The key biomarkers for LSCs were identified by flow cytometry. Fucosyltransferase genes were screened by qRT-PCR, and FUT4 was focused. Effect of FUT4 on LSCs malignancy was determined by CCK8 assay, sphere formation assay, immunofluorescence staining, apoptosis and in vivo xenografts experiments. The linkage of FUT4 promoter and Sp1 was confirmed by dual-luciferase reporter gene assay. ChIP-PCR assay was used to show the directly binding of Sp1 and FUT4 promoter. Activity of Wnt//β-catenin pathway was determined by western blot. Overall survival curves were diagrammed by Kaplan-Meier analysis. Results: Here, the expressional profiles of 11 fucosyltransferase genes were different comparing LSCs and non-LSCs of KG-1a and MOLM13 cells, whereas CD34 + CD38- cells exhibited higher expression of FUT4. Functionally, alteration of FUT4 in CD34 + CD38- cells modulated LSCs malignant behaviors both in vitro and in vivo. Transcriptional inhibitor actinomycin D (Act D) or translational inhibitor cycloheximide (CHX) prevented LSCs progression, and Sp1 was identified as the efficient regulator of FUT4 transcription. Moreover, miR-29b directly affected the binding of Sp1 and FUT4 promoter region, which further mediated LSCs proliferation, apoptosis and drug-resistance through fucosylated-CD44 via activation of Wnt/β-catenin pathway. Clinically, Sp1 and FUT4 were up-regulated and positively correlated with poor overall survival of AML patients. Conclusion: These data indicated that miR-29b/Sp1/FUT4 axis promoted the malignant behaviors of LSCs by regulating fucosylated CD44 via Wnt/β-catenin pathway. Identifying LSCs surface markers and targeting LSCs were important for the development of potential therapies in AML. [ABSTRACT FROM AUTHOR]

Aim: To develop a method capable of identifying human corneal limbal stem cells (LSCs) and follow their proliferation and migration in the epithelium., Materials and Methods: Ten fresh matched pairs of cadaveric normal human corneas were obtained from donors. Carboxyfluorescein diacetate succinimidyl ester (CFSE) was used to target LSCs. The distribution of CFSE-positive cell clusters was analyzed by fluorescence microscopy by counterstaining with 4',6-diamidino-2-phenylindole (DAPI). Fluorescence was digitally recorded for seven days, and the rate of cell movement was determined., Results: CFSE-labeled cells were tracked in corneas. Analysis of time sequences revealed that they moved centripetally. Daily average CFSE-labeled LSC movement was 0.073±0.01 cm (±SD)., Conclusion: CFSE allowed us to identify LSCs and to track their centripetal migration from the limbal basal layer to the anterior ocular surface. This experimental system appears to be a valuable tool for further studies on corneal epithelial cell migration and proliferation., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Liver is the second most transplanted organ according to United network for organ sharing. Due to shortage of compatible donors, surgical difficulties, immunological hindrance, and high postoperative cost, stem cell therapy is an attractive substitute of liver transplant for millions of patients suffering from hepatic failure. Due to several technical limitations such as viral integration, inefficient differentiation, and adult phenotypes and epigenetic memory of fibroblasts, induced pluripotent stem cells, mesenchymal stem cells, or induced hepatocyte may not present a great clinical substitute for liver transplant. We pioneered a novel technology for robust expansion of quiescent liver stem cells (LSCs) from mice via utilizing of Hedgehog agonist HhAg1.5 for 3 weeks. These expanded LSCs retained stem-like properties after multiple passaging and differentiated to hepatocytes and cholangiocytes. Grafting of ex vivo expanded LSCs in Fah -/- Rag2 -/-  Il2rg -/- knockout mice, significantly increased life span compared to control group (P < 0.001). Thus in this study, we provide a promising viable substitute for primary hepatocytes for regenerative medicine and for life-threatening metabolic liver diseases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Leukemia is a group of progressive hematologic malignancies derived from stem cells in bone marrow which causes a large number of cancer deaths. Even with treatment such as traditional chemotherapy, targeted therapy, and allogeneic stem cell transplantation (allo-HSCT), many patients suffer from relapse/refractory disease, and the overall survival is dismal. Leukemic stem cells (LSCs) are induced by gene mutations and undergo an aberrant and poorly regulated proliferation process which is involved in the evolution, relapse, and drug-resistance of leukemia. Emerging studies demonstrate that CD123, the interleukin 3 receptor alpha (IL-3Rα), is highly expressed in LSCs, while not normal hematopoietic stem cells (HSCs), and associates with treatment response, minimal residual disease (MRD) detection and prognosis. Furthermore, CD123 is an important marker for the identification and targeting of LSCs for refractory or relapsed leukemia. Anti-CD123 target-therapies in pre-clinical studies and clinical trials confirm the utility of anti-CD123 neutralizing antibody-drugs, CD3×CD123 bispecific antibodies, dual-affinity retargeting (DART), and anti-CD123 chimeric antigen receptor-modified T-cell (CAR-T) therapies in progress. This review summarizes the most recent progress on the study of CD123 biology and the development of novel CD123-targeted therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Despite successful remission induction, recurrence of acute myeloid leukemia (AML) remains a clinical obstacle thought to be caused by the retention of dormant leukemic stem cells (LSCs). Using chemotherapy-treated AML xenografts and patient samples, we have modeled patient remission and relapse kinetics to reveal that LSCs are effectively depleted via cell-cycle recruitment, leaving the origins of relapse unclear. Post-chemotherapy, in vivo characterization at the onset of disease relapse revealed a unique molecular state of leukemic-regenerating cells (LRCs) responsible for disease re-growth. LRCs are transient, can only be detected in vivo, and are molecularly distinct from therapy-naive LSCs. We demonstrate that LRC features can be used as markers of relapse and are therapeutically targetable to prevent disease recurrence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Canonical NF-κB signaling is constitutively activated in acute myeloid leukemia (AML) stem cells and is required for maintenance of the self-renewal of leukemia stem cells (LSCs). However, any potential role for NF-κB non-canonical signaling in AML has been largely overlooked. Here, we report that stabilization of NF-κB-inducing kinase (NIK) suppresses AML. Mechanistically, stabilization of NIK activates NF-κB non-canonical signaling and represses NF-κB canonical signaling. In addition, stabilization of NIK-induced activation of NF-κB non-canonical signaling upregulates Dnmt3a and downregulates Mef2c, which suppresses and promotes AML development, respectively. Importantly, by querying the connectivity MAP using up- and downregulated genes that are present exclusively in NIK-stabilized LSCs, we discovered that verteporfin has anti-AML effects, suggesting that repurposing verteporfin to target myeloid leukemia is worth testing clinically. Our data provide a scientific rationale for developing small molecules to stabilize NIK specifically in myeloid leukemias as an attractive therapeutic option., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Although Caesarean sections (CSs) are among the most commonly undertaken procedures in the world, there are wide variations in the surgical techniques used. This study aimed to: (a) review the surgical techniques used for CS by obstetricians working in a tertiary hospital in Singapore; (b) compare the techniques with those recommended in evidence-based guidelines; and (c) examine the relationship between the technique used and the level of seniority of the surgeons., Methods: Data on 490 CSs performed in Singapore General Hospital (SGH) between 1 August 2013 and 30 June 2014 was collected from the Delivery Suite database and reviewed. The surgical techniques studied were closure of the pelvic and parietal peritoneum, closure of the uterine layer, use of surgical drains and use of postoperative thromboprophylaxis., Results: A total of 486 CSs were analysed after four cases were excluded due to missing data. Most fetal head deliveries were manual. The majority of surgeons did not close the peritoneum; most of those who did were senior surgeons. Double-layer uterine closures were done for all cases and drain usage was rare. 2.0% of the patients received grossly inadequate thromboprophylaxis., Conclusion: The surgical techniques currently practised in SGH are closely aligned with those of the evidence-based guidelines. Peritoneal closure appears to be associated with the surgeon's early training, with a greater number of senior surgeons being less willing to abandon this step. Greater vigilance in implementing appropriate thromboprophylaxis is recommended., (Copyright: © Singapore Medical Association)

Nuclear receptor co-repressor (N-CoR) is the key component of generic co-repressor complex essential for the transcriptional control of genes involved in cellular hemostasis. We have recently reported that N-CoR actively represses Flt3, a key factor of hematopoietic stem cells (HSC) self-renewal and growth, and that de-repression of Flt3 by the misfolded N-CoR plays an important role in the pathogenesis of promyelocytic and monocytic acute myeloid leukemia (AML). The leukemic cells derived from the promyelocytic and monocytic AML are distinctly characterized by the ectopic reactivation of stem cell phenotypes in relatively committed myeloid compartment. However, the molecular mechanism underlying this phenomenon is not known. Here, we report that N-CoR function is essential for the commitment of primitive hematopoietic cells to the cells of myeloid lineage and that loss of N-CoR function due to misfolding is linked to the ectopic reactivation of generic stem cell phenotypes in promyelocytic and monocytic AML. Analysis of N-CoR and Flt3 transcripts in mouse hematopoietic cells revealed a positive correlation between N-CoR level and the commitment of myeloid cells and an inverse correlation between N-CoR and Flt3 levels in primitive as well as committed myeloid cells. Enforced N-CoR expression in mouse HSCs inhibited their growth and self-renewal potentials and promoted maturation toward cells of myeloid lineage, suggesting a role of N-CoR in the commitment of cells of myeloid lineage. In contrast to AML cells with natively folded N-CoR, primary and secondary promyelocytic and monocytic AML cells harboring the misfolded N-CoR were highly positive for Flt3 and myeloid antigen-based HSC marker CD34. Genetic and therapeutic restoration of N-CoR conformation significantly down-regulated the CD34 levels in monocytic AML cells, suggesting an important role of N-CoR in the suppression of CD34-based HSC phenotypes. These findings collectively suggest that N-CoR is crucial for the commitment of primitive hematopoietic cells to cells of myeloid lineage and that misfolded N-CoR may contribute to transformation of committed myeloid cells through the ectopic reactivation of Flt3/CD34-based stem cell phenotypes in promyelocytic and monocytic AML. Moreover, these findings provide novel mechanistic insights into the formation of leukemic stem cells in subsets of AML and identify the misfolded N-CoR as a subtype-specific biomarker of AML.