Different Types Of Leukemia Research Articles

State-of-Art of Cellular Therapy for Acute Leukemia.

With recent clinical breakthroughs, immunotherapy has become the fourth pillar of cancer treatment. Particularly, immune cell-based therapies have been envisioned as a promising treatment option with curative potential for leukemia patients. Hence, an increasing number of preclinical and clinical studies focus on various approaches of immune cell-based therapy for treatment of acute leukemia (AL). However, the use of different immune cell lineages and subsets against different types of leukemia and patient disease statuses challenge the interpretation of the clinical applicability and outcome of immune cell-based therapies. This review aims to provide an overview on recent approaches using various immune cell-based therapies against acute B-, T-, and myeloid leukemias. Further, the apparent limitations observed and potential approaches to overcome these limitations are discussed.

Janus Kinases in Leukemia.

Simple SummaryJanus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is a crucial cell signaling pathway that drives the development, differentiation, and function of immune cells and has an important role in blood cell formation. Mutations targeting this pathway can lead to overproduction of these cell types, giving rise to various hematological diseases. This review summarizes pathogenic JAK/STAT activation mechanisms and links known mutations and translocations to different leukemia. In addition, the review discusses the current therapeutic approaches used to inhibit constitutive, cytokine-independent activation of the pathway and the prospects of developing more specific potent JAK inhibitors.Janus kinases (JAKs) transduce signals from dozens of extracellular cytokines and function as critical regulators of cell growth, differentiation, gene expression, and immune responses. Deregulation of JAK/STAT signaling is a central component in several human diseases including various types of leukemia and other malignancies and autoimmune diseases. Different types of leukemia harbor genomic aberrations in all four JAKs (JAK1, JAK2, JAK3, and TYK2), most of which are activating somatic mutations and less frequently translocations resulting in constitutively active JAK fusion proteins. JAKs have become important therapeutic targets and currently, six JAK inhibitors have been approved by the FDA for the treatment of both autoimmune diseases and hematological malignancies. However, the efficacy of the current drugs is not optimal and the full potential of JAK modulators in leukemia is yet to be harnessed. This review discusses the deregulation of JAK-STAT signaling that underlie the pathogenesis of leukemia, i.e., mutations and other mechanisms causing hyperactive cytokine signaling, as well as JAK inhibitors used in clinic and under clinical development.

The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia.

Chronic inflammation contributes to the development and progression of various tumors. Especially where the inflammation is mediated by cells of the innate immune system, the NLRP3 inflammasome plays an important role, as it senses and responds to a variety of exogenous and endogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The NLRP3 inflammasome is responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 and for the induction of a type of inflammatory cell death known as pyroptosis. Overactivation of the NLRP3 inflammasome can be a driver of various diseases. Since leukemia is known to be an inflammation-driven cancer and IL-1β is produced in elevated levels by leukemic cells, research on NLRP3 in the context of leukemia has increased in recent years. In this review, we summarize the current knowledge on leukemia-promoting inflammation and, in particular, the role of the NLRP3 inflammasome in different types of leukemia. Furthermore, we examine a connection between NLRP3, autophagy and leukemia.

Urinarni metaboliti kao indikatori izloženosti ljudi hemijskim karcinogenima

Population exposure to environmental chemical carcinogens is a growing public health problem. Carcinogenic chemicals may be classified into two groups: genotoxic and non-genotoxic. A genotoxic chemical has a potential to induce the development of cancer, either in direct interaction with DNA or with cell structures, which are responsible for the maintenance of genome integrity. A non-genotoxic chemical has a potential to induce cancer indirectly by entering the processes of cancer etiopathogenesis. Previous research studies indicate that inorganic arsenic compounds may be associated with various malign diseases (lung cancer, urinary bladder cancer, skin, kidney, liver and prostate cancer). Inorganic arsenic is mainly present in meat, dairy products and grains, while organic arsenic (arsenobetaine) is present in seafood, fruit and vegetables. Benzene metabolites are associated with different types of leukemias and lymphomas, benzidine with bladder cancer, nickel with lung cancer, chromium compounds with lung cancer, nose and nasal sinus cancer. The greatest occupational exposure to benzene is in industry (leather, electronic device, shoes, sports equipment), while people may come into contact with benzidine through consumer goods (leather products, clothes, toys). The highest concentrations of nickel were measured in the beans, walnuts and grains. Cadmium and cadmium compounds cause lung cancer, and influence the occurrence of renal and prostate cancer. The risk of hepatocellular carcinoma is significantly increased in respondents with high concentrations of urinary metabolites of aflatoxin (aflatoxin N7-gvanine adducts). Lindane isomers are present in dairy products, meat, fish, poultry, garden fruit, oils and lipids, leaf and root vegetables and sugar, and they cause non-Hodgkin lymphoma. There is a positive correlation between the consumption of Aristolochia plants and the occurrence of urothelial carcinoma. There are no screening examinations for the identification of persons who are at great risk of developing malign disease in the next 10 or 20 years. As for the prevention of malign diseases, it is necessary to put an accent on finding the adequate methods for determining the concentrations of urinary metabolites for toxic chemical carcinogens and define their risk values.

Epigenetic Modifications in Acute Lymphoblastic Leukemia: From Cellular Mechanisms to Therapeutics.

Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood, and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understanding the underlying mechanism of acute lymphoblastic leukemia (ALL), especially epigenetic alterations as a driving force in the development of ALL opens a new era of investigation for developing promising strategy, beyond available conventional therapy. This review will focus on a better understanding of the epigenetic mechanisms in cancer development and progression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and microRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel, well-suited approaches against ALL. According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifications, particularly DNA hyper-methylation, histone modification, and miRNA alteration.

Role of magnetic resonance imaging in characterization of central nervous system lesions in pediatric patients with leukemia and post-treatment complications

BackgroundLeukemia is one of the most common fatal diseases in pediatric oncology. Recently, advances in drug therapy have improved the prognosis of acute leukemia with event-free survival of up to 60%; however, complications and adverse effects of the disease and anti-leukemic treatment have also increased. The CNS complications of leukemia can be classified into those that developed directly or indirectly from the underlying leukemic process and those that can be related to antileukemic therapy. MRI had improved early detection of CNS complications and proper management. The study aims to characterize the MRI findings caused by the leukemic involvement of CNS structures and treatment-associated CNS complications and assess its value in early management and avoidance of long-term side effects.ResultsThe patient’s age ranged from 2 to 18 years with different types of leukemia classified regarding the time of presentation as pretreatment, during treatment phases, and post-treatment. Different MRI abnormalities were recorded and clinically correlated.ConclusionThe neurological complications of leukemia have common presenting symptoms but varying imaging abnormalities. To reach the correct diagnosis, the presenting signs, symptoms, and laboratory data must be considered along with the radiologic findings. A diagnostic algorithm using conventional, post-contrast MRI, MR venography, along with diffusion-weighted MRI was of great value in early detection and differentiation of different CNS lesions detected in pediatric patients with leukemia and post-treatment CNS complications.

ALL-310: The Prognostic Impact of Lipid Profiles in Adult Egyptian Acute Leukemia Patients

Context Acute leukemia is a malignant disorder that results from clonal proliferation of lymphoid and myeloid blast cells. Several studies have reported some changes in lipid metabolism at time of diagnosis of leukemia. Although investigators have reported decreased total cholesterol, decreased high density lipid (HDL), and elevated triglycerides (TG) in leukemic patients; there is a controversy about these changes among different types of leukemia and between children and adult patients, in addition to different data about their impact on prognosis. Objective Lipid profiles were examined at the time of diagnosis of acute leukemia in order to correlate them with response to therapy. Design A prospective study included 50 newly diagnosed patients with acute leukemia between 2018 and 2019. Setting The study was carried out at Oncology Center Mansoura University (OCMU). Patients Thirty-four patients were diagnosed with AML (68%), while 16 patients diagnosed with ALL (32%). Twenty-five patients were male (50%), and 25 were female (50%). Interventions Lipid profile and body mass index (BMI) were obtained. Main outcome measures Complete response rate and overall survival. Results Overweight/obese patients showed statistically significant association with female patients than male patients (p=0.009). By comparing the lipid profile between overweight/obese patients and other patients, there was no statistically significant association. In addition, 76.7% of AML patients were overweight orobese (p 0.015), and 81.3% of ALL patients showed hypertriglyceridemia (p=0.014). There was no statistically significant association between lipid profile and complete response (CR) rate; however, there was a marginally significant association between non-CR rate and overweight and obese patients (p=0.051). In addition, there was no impaction of BMI or lipid profile in overall survival among acute leukemia patients. Conclusions Female acute myeloid leukemia patients were more commonly associated with overweight and obesity, and high TG level was found to be associated with acute lymphoid leukemia. Changes in lipid profile showed no impact on complete response rate and overall survival in acute leukemia patients.

Nuclear Receptors as Potential Therapeutic Targets for Myeloid Leukemia.

The nuclear receptor (NR) superfamily has been studied extensively in many solid tumors and some receptors have been targeted to develop therapies. However, their roles in leukemia are less clear and vary considerably among different types of leukemia. Some NRs participate in mediating the differentiation of myeloid cells, making them attractive therapeutic targets for myeloid leukemia. To date, the success of all-trans retinoic acid (ATRA) in treating acute promyelocytic leukemia (APL) remains a classical and unsurpassable example of cancer differentiation therapy. ATRA targets retinoic acid receptor (RAR) and forces differentiation and/or apoptosis of leukemic cells. In addition, ligands/agonists of vitamin D receptor (VDR) and peroxisome proliferator-activated receptor (PPAR) have also been shown to inhibit proliferation, induce differentiation, and promote apoptosis of leukemic cells. Encouragingly, combining different NR agonists or the addition of NR agonists to chemotherapies have shown some synergistic anti-leukemic effects. This review will summarize recent research findings and discuss the therapeutic potential of selected NRs in acute and chronic myeloid leukemia, focusing on RAR, VDR, PPAR, and retinoid X receptor (RXR). We believe that more mechanistic studies in this field will not only shed new lights on the roles of NRs in leukemia, but also further expand the clinical applications of existing therapeutic agents targeting NRs.

Role of Stem-Cell Transplantation in Leukemia Treatment.

Stem cells (SCs) play a major role in advanced fields of regenerative medicine and other research areas. They are involved in the regeneration of damaged tissue or cells, due to their self-renewal characteristics. Tissue or cells can be damaged through a variety of diseases, including hematologic and nonhematologic malignancies. In regard to this, stem-cell transplantation is a cellular therapeutic approach to restore those impaired cells, tissue, or organs. SCs have a therapeutic potential in the application of stem-cell transplantation. Research has been focused mainly on the application of hematopoietic SCs for transplantation. Cord blood cells and human leukocyte antigen–haploidentical donors are considered optional sources of hematopoietic stem–cell transplantation. On the other hand, pluripotent embryonic SCs and induced pluripotent SCs hold promise for advancement of stem-cell transplantation. In addition, nonhematopoietic mesenchymal SCs play their own significant role as a functional bone-marrow niche and in the management of graft-vs-host disease effects during the posttransplantation process. In this review, the role of different types of SCs is presented with regard to their application in SC transplantation. In addition to this, the therapeutic value of autologous and allogeneic hematopoietic stem–cell transplantation is assessed with respect to different types of leukemia. Highly advanced and progressive scientific research has focused on the application of stem-cell transplantation on specific leukemia types. We evaluated and compared the therapeutic potential of SC transplantation with various forms of leukemia. This review aimed to focus on the application of SCs in the treatment of leukemia.

Studies on the morphology of leukaemic blast cells in relation to haematological parameters

A combination of haematological parameters with morphological evaluation of peripheral blood and bone marrow blast cells is crucial for leukaemia diagnosis. FAB (French– American–British) classification is a simple and powerful diagnostic tool for leukaemia in developing countries like India. Differentiation block in the early stages of haematopoiesis and morphological characteristics of leukemic blast cells are directly related to haematological parameters. The present study is an approach to increase understanding of the simple morphological FAB classification of leukaemia in relation to haematological parameters. The present study revealed that Chronic Myeloid Leukaemia (CML) was the most common type of leukaemia , followed by Acute Myeloid Leukaemia, Acute Lymphoid Leukaemia (ALL), and Chronic Lymphoid Leukaemia (CLL) in Nagpur. Most of the cases of Acute Leukaemia had severe anaemia and thrombocytopenia. Highest variation was found in Total WBCs count of different types of leukaemia , particularly in different subtypes of AML. The present study also suggested that FAB classification is not outdated, but it does require continuous revalidation and other procedures for refinement.

Analysis of Four Types of Leukemia Using Gene Ontology Term and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment Scores.

Leukemia is the second common blood cancer after lymphoma, and its incidence rate has an increasing trend in recent years. Leukemia can be classified into four types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML). More than forty drugs are applicable to different types of leukemia based on the discrepant pathogenesis. Therefore, the identification of specific drug-targeted biological processes and pathways is helpful to determinate the underlying pathogenesis among such four types of leukemia. In this study, the gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were highly related to drugs for leukemia were investigated for the first time. The enrichment scores for associated GO terms and KEGG pathways were calculated to evaluate the drugs and leukemia. The feature selection method, minimum redundancy maximum relevance (mRMR), was used to analyze and identify important GO terms and KEGG pathways. Twenty Go terms and two KEGG pathways with high scores have all been confirmed to effectively distinguish four types of leukemia. This analysis may provide a useful tool for the discrepant pathogenesis and drug design of different types of leukemia.

Leukemia cutis in a medical center in southern Taiwan: A retrospective study of 42 patients

Leukemia cutis (LC), by definition, is the infiltration of neoplastic leukocytes in the skin. The overall incidence of LC is rare. We aimed to investigate the association between clinical characteristics, classifications and prognosis among different types of LC in Taiwan. We performed a retrospective analysis of forty-two patients with histopathology proven LC based on skin biopsies in a medical center in Southern Taiwan from 1997 to 2018. The study involved medical records of the patients, clinical manifestations, and outcomes according to different types of leukemia. This series consisted of 27 males and 15 females, and the mean age was 55.7 years old. The most common cutaneous features were papules (38%) and nodules (29%), followed by plaques (16%) and ulcers (10%). The most commonly affected sites were the trunk (33%) and extremities (31.5%), although generalized distribution (14%) was not rare. The prognosis of LC was very poor, 76.2% of patients (32/42) died during the follow-up, and the median survival time was 7.2 months (95% CI, 4.53-9.87 months). No statistical significance was found (P=0.068 for survival curves) among different types of LC. This study was the first large-scale research in regarding to LC of Han Chinese. The commonest clinical presentations were papules and nodules, and the predilection sites were trunk and extremities. Besides, there was the high frequency of LC from AML and MDS in Taiwan. Clinicians should pay more attention to the leukemia patients with extramedullary manifestations due to poor survival outcomes.

A general view of CD33+ leukemic stem cells and CAR-T cells as interesting targets in acute myeloblatsic leukemia therapy.

Acute myeloblastic leukemia (AML) is the most frequent acute leukemia in adulthood with very poor overall survival rates. In the past few decades, significant progresses had led to the findings of new therapeutic approaches and the better understanding of the molecular complexity of this hematologic malignancy. Leukemic stem cells (LSCs) play a key role in the initiation, progression, regression, and drug resistance of different types of leukemia. The cellular and molecular characteristics of LSCs and their mechanism in the development of leukemia had not yet been specified. Therefore, determining their cellular and molecular characteristics and creating new approaches for targeted therapy of LSCs is crucial for the future of leukemia research. For this reason, the recognition of surface maker targets on the cell surface of LSCs has attracted much attention. CD33 has been detected on blasts in most AML patients, making them an interesting target for AML therapy. Genetic engineering of T cells with chimeric antigen receptor (CAR-T cell therapy) is a novel therapeutic strategy. It extends the range of antigens available for use in adoptive T-cell immunotherapy. This review will focus on CAR-T cell approaches as well as monoclonal antibody (mAB)-based therapy, the two antibody-based therapies utilized in AML treatment.

Synthesis and Characterization of Arsenic(III) Oxide Nanoparticles as Potent Inhibitors of MCF 7 Cell Proliferation through Proapoptotic Mechanism

Recent advances in the nanosciences have revolutionized the diagnosis and treatment of diseases like cancers. Arsenic(III) trioxide, best known as a toxic agent, is routinely used in treating different types of leukemia. Besides its application as a chemotherapeutic drug for treating acute promyelocytic leukemia, several attempts have been made to use arsenic trioxide (ATO) against solid tumors. This is however, restricted because of the rapid renal clearance and dose-associated side effects of ATO. This work aims to address these limitations of ATO in chemotherapy by synthesizing biocompatible human serum albumin coated arsenic trioxide nanoparticles (HSA-ATONPs) by an alkaline hydrothermal process, taking sodium arsenate as a precursor. Compared with bulk ATO, these are found to have better cytotoxicity as indicated by an in vitro study with the cancer cell line MCF7. As envisaged by transmission electron microscopy, canonical signs of apoptosis were observed in the MCF 7 cells treated with HSA-ATONPs, confirmed by Annexin V-FITC staining. The study thus, reports an augmentation of the chemotherapeutic potential of arsenic trioxide in its nanoparticulate form with its surface functionalization of human serum albumin.

FBW7 in hematological tumors.

F-box and WD repeat domain-containing protein 7 (FBW7), also known as FBXW7, AGO or hCDC4, is an F-box protein with seven tandem WD40 repeats. FBW7 is a key substrate recognition subunit of the Skp1-Cul1-F-box-protein E3 ubiquitin ligase. FBW7 targets for ubiquitination and destruction of numerous crucial transcription factors and protooncogenes, including cyclin E, c-Myc, c-Jun, Notch and MCL-1. FBW7 is a well-characterized tumor suppressor, and its gene is frequently mutated or deleted in various types of human cancer, including colorectal cancer, gastric cancer, ovarian cancer and different types of leukemia. Accumulating evidence indicates that the aberrant expression of FBW7 is involved in the development of hematological tumors, including T cell acute lymphoblastic leukemia, adult T cell leukemia/lymphoma, chronic lymphocytic leukemia and multiple myeloma. The present review will describe the latest findings on the role of FBW7 in hematological tumors, in order to identify a novel target for future therapies.

Applications of PET in Diagnosis and Prognosis of Leukemia.

As a malignant hematopoietic stem cell disease, leukemia remains life-threatening due to its increasing incidence rate and mortality rate. Therefore, its early diagnosis and treatment play a very important role. In the present work, we systematically reviewed the current applications and future directions of positron emission tomography (PET) in patients with leukemia, especially 18F-FDG PET/CT. As a useful imaging approach, PET significantly contributes to the diagnosis and treatment of different types of leukemia, especially in the evaluation of extramedullary infiltration, monitoring of leukemia relapse, detection of Richter’s transformation (RT), and assessment of the inflammatory activity associated with acute graft versus host disease. Future investigations should be focused on the potential of PET/CT in the prediction of clinical outcomes in patients with leukemia and the utility of novel radiotracers.

The double jeopardy of leukemia and dengue: A report of three cases

Dengue is predominantly a self-limiting illness. The association of dengue with new onset of leukemia has been rarely reported. We describe herein a series of three patients diagnosed with acute lymphoblastic leukemia, chronic myeloid leukemia, and acute promyelocytic leukemia who presented with concurrent dengue infection at a tertiary care institute in the southwestern coastal region of India. In spite of the different types of leukemias, we observed similar trends in their blood parameters, which were comparable with those of nonleukemic dengue patients. The transfusion profile of each of these patients is described. We could conclude that even in the presence of leukemia, dengue tends to be self-limited. No such comparative case reports have been published so far, and with an increasing incidence of dengue in the world, the occurrence of the two might not remain a remote possibility.

Final Development of the First Generic Quality of Life and Symptoms Measure Specific for Hematological Malignancies: The HM-PRO

Background Health related quality of life (HRQoL) of patients with hematological malignancies (HMs) is greatly affected by the disease and the treatment and this has not been captured in a systematic manner in routine clinical practice. A systematic review of the HRQoL issues and instruments used in HM showed gaps between what is important to patients and what is being measured. The aims of this study were to develop and validate an instrument for measuring the impact of HMs and their treatment on patients' HRQoL and symptoms in daily clinical practice. Methods A multicentre Ethics approval was obtained from the National Research Ethics Service (NRES) of South West Bristols, UK. Adult patients with HM as per 2016 Revised WHO classification, capable of reading English and able to give written informed consent, were recruited from inpatient/outpatient clinics of seven secondary care hospitals in England and Wales for all phases of the study (Table 1). The qualitative study employed semi-structured face-to-face interviews. The generated items were then discussed in data definition panel meeting for inclusion in the prototype version of the new instrument. The content validation was followed by item reduction phase where number of items were reduced to more confined set of items. The version of HM-PRO developed after exploratory factory analysis and confirmatory factor analysis was used to perform Rasch modeling. In next step for demonstrating validity of the HM-PRO, construct and convergent/divergent validity was studied. The score banding was developed and MCID was established. Results Face-to-face interviews were performed in 129 patients. The content analysis of the transcribed interviews resulted in a comprehensive item pool. The generated items included in the prototype HM-PRO, were 34 items for impact on HRQoL category (Part A) and 23 items representing disease signs and symptoms (Part B). The version after exploratory and confirmatory factor analysis was used to perform Rasch modeling in 182 patients resulting in 24 items in Part A and 18 items in Part B. The reliability testing (n=150) showed strong stability of measurement with Cronbach's alpha estimates of the HM-PRO for both assessment points (t1 and t2) above 0.9 for Part A, and above 0.8 for Part B. The intraclass correlation coefficient (ICC) for four domains of Part A was 0.85 - 0.91 and >0.8 for the overall scores of Part A and Part B, for all ten diagnoses, confirming strong reliability of the HM-PRO. Construct and convergent/divergent validity were studied in 905 cases. The HM-PRO scores correlated with scores of EORTC QLQ-C30 and FACT-G, both at the scale and at individual item levels. The univariate regression analysis confirmed a strong relationship between the HM-PRO and the other two measures. For the majority of regression models, the HM-PRO domains and individual items explained more than 50% of the variance in domain and item scores of EORTC QLQ-C30 and FACT-G, confirming the construct validity. The responsiveness testing (n=299) showed that HM-PRO is responsive to small but clinically important change in patients' HRQoL. The score banding was developed for the HM-PRO for its interpretability in to day-to-day clinical practice. The MCID for Part A based on standard error of mean was 6.2 and for PART B 5.9 points. It therefore was prudent, for practical reasons, to propose MCID of '6' for the HM-PRO. Conclusion This study provides evidence of the value of HM-PRO through content validity, reliability, construct validity, responsiveness and interpretability. The current research has developed and validated the English version of the HM-PRO. Further studies are being carried out to validate the instrument in several global languages for cross-cultural adaptation. Furthermore, the Acute Leukaemia Advocates Network (ALAN) is using the HM-PRO in a multi-country survey including five European (French, German, Italian, Portuguese, Spanish) and five non-European countries (Chinese, Hebrew, Korean, Japanese, Russian) to generate data in order to understand the impact of the disease and treatment on patients with different types of leukaemia. The data collected from this survey will be used to further validate the HM-PRO specifically in patients with leukaemia and potentially improve management of patients and their treatment. The HM-PRO has good potential to be widely used in daily clinical practice as well as in hemato-oncology clinical trials. Disclosures Kell: Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Fielding:Incyte: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Amgen: Consultancy. Collins:Gilead: Consultancy, Honoraria. Salek:Pfizer: Honoraria, Speakers Bureau; Agios Pharmaceuticals, Inc.: Consultancy, Honoraria; Merck: Consultancy.

N-MYC INDUCES VARIOUS TYPES OF MOUSE ACUTE LEUKEMIA

N-Myc plays a role in the regulation of proliferation, differentiation, and survival of hematopoietic stem cells (HSCs) and leukemogenesis. We studied the cell of origin in the mouse acute leukemia model by N-Myc-overexpression. Our single cell RNA-seq data showed that N-Myc is restrictively expressed in HSCs and hematopoietic progenitor cells (HPCs) whereas c-Myc, but not L-Myc, is widely expressed in a variety of hematopoietic cells. HSC1, HSC2, HPC1, HPC2, and HPC3 with different self-renewal and differentiation potentials were isolated from the bone marrow of adult B6 mice. These cells were retrovirally overexpressed with N-Myc and transplanted into lethally irradiated mice with competitor cells. Acute leukemia developed from all these populations. Notably, not only B cell acute lymphoid leukemia (B-ALL), but also T cell ALL (T-ALL), acute myeloid leukemia (AML), acute undifferentiated leukemia (AUL), and mixed phenotype acute leukemia (MPAL) developed. Metascape analysis of RNA-seq data showed that RNA profiles each from B-ALL, T-ALL, AML and AUL samples were enriched in special cellular signaling pathways. Collectively, the multiple cells of origin suggested that the self-renewal and differentiation potentials of cells were not related to leukemogenesis induced by N-Myc-overexpression. In addition, whole genome sequencing data suggested that retroviral integration sites play a role in the development of different types of leukemia.

Prevalence of Acute and Chronic Forms of Leukemia in Various Regions of Khyber Pakhtunkhwa, Pakistan: Needs Much More to be done!

Background and objective: Leukemia is one of the fatal diseases and their morbidity and mortality rates increases day by day all over the world. This piece of research study was designed in order to find out the prevalence of different types of leukemia in Khyber Pakhtunkhwa, Pakistan during January 2015 to December 2016.
 Material and Method: The retrospective research study was carried out at Institute of Radiotherapy and Nuclear Medicine (IRNUM) Peshawar. A data of 400 admitted patients of leukemia were evaluated.
 Result: It was observed that acute leukemia (80%) was more prevalent than chronic leukemia (20%). Amongst types of leukemia, Acute Lymphocytic Leukemia (ALL) 49.5% (n=198) was more prevalent than Acute Myelogenous Leukemia (AML) 31.25% (n=125), Chronic Myelogenous Leukemia (CML) 10% (n=40) and Chronic Lymphocytic Leukemia (CLL) 9.25% (n=37) was less prevalent in this study. It was also found that leukemia was more prevalent in male patients 64.5% (n=258) as compared to females 35.5% (n=142) and male to female ratio was 1.8:1. Most of the patients were under the age of 20 years.
 Conclusion: Acute leukemia was more prevalent than chronic leukemia during this study in this part of the country and needs to be address.
 Bangladesh Journal of Medical Science Vol.18(2) 2019 p.222-227