Effect of Chemotherapy for Acute Myelogenous Leukemia on Hematopoietic and fibroblast Marrow Progenitors

Total Page:16

File Type:pdf, Size:1020Kb

Effect of Chemotherapy for Acute Myelogenous Leukemia on Hematopoietic and fibroblast Marrow Progenitors Bone Marrow Transplantation, (1997) 20, 465–471 1997 Stockton Press All rights reserved 0268–3369/97 $12.00 Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors C Carlo-Stella1, A Tabilio2, E Regazzi1, D Garau1, R La Tagliata3, S Trasarti3, C Andrizzi3, M Vignetti3 and G Meloni3 1Department of Hematology, University of Parma; 2Department of Hematology, University of Perugia; and 3Department of Cellular Biotechnologies and Hematology, ‘La Sapienza’ University, Rome, Italy Summary: Keywords: hematopoietic progenitors; microenviron- mental progenitors; acute myelogenous leukemia; chemo- Since reduced marrow cellularity and prolonged pancy- therapy; LTC-IC; hematopoietic engraftment topenia following autologous bone marrow transplan- tation (ABMT) have been frequently observed in patients with acute myelogenous leukemia (AML) included in the AML10 GIMEMA/EORTC trial, the The structural integrity of the hematopoietic system is question was raised to what extent hematopoietic and maintained by a relatively small population of self- microenvironmental progenitor cells were involved in renewing stem cells which can differentiate to produce pro- these patients. Marrow hematopoietic progenitors were genitors committed to terminal maturation.1 The develop- investigated by a short-term methylcellulose assay ment of hematopoietic cells in vivo occurs in intimate quantitating multipotent CFU-Mix, erythroid BFU-E association with a heterogeneous population of mesenchy- and granulocyte–macrophage CFU-GM, as well as a mal, connective tissue type cells and their associated long-term assay quantitating long-term culture- biosynthetic products, which constitute the stromal tissue initiating cells (LTC-IC). The marrow microenviron- of the bone marrow.2 Stromal cells of the hematopoietic ment was studied by evaluating the incidence of fibro- microenvironment include fibroblasts, endothelial cells, blastoid progenitors (CFU-F) and the capacity of stro- adipocytes, and macrophages.2 Based on a number of stud- mal layers to support allogeneic hematopoietic ies,3 the existence of self-renewing stromal stem cells with progenitors. As compared to normal controls (n = 57), multilineage differentiation capacity and capable of gener- AML patients (n = 26) showed a statistically significant ating progenitors with restricted development potential, reduction of the mean (± s.e.m.) number of CFU-Mix including fibroblast, osteoblast and chondrocyte progeni- (5.3 ± 0.6 vs 0.8 ± 0.2, P < 0.0001), BFU-E (68 ± 5 vs tors, has been hypothesized.4–6 20 ± 4, P < 0.0001), CFU-GM (198 ± 11 vs 144 ± 15, P Standard- and high-dose therapies currently used for the < 0.008), and LTC-IC (302 ± 46 vs 50 ± 8, P < 0.001). treatment of hematological and nonhematological malig- The mean (± s.e.m.) incidence of marrow CFU-F was nancies induce transient or permanent damage of hemato- not significantly reduced as compared to normal con- poietic and stromal progenitor cell compartments.7,8 trols (48 ± 6 vs 52 ± 7, P < 0.73). Seventeen AML stro- Despite such chemotherapy-induced defective progenitor mal layers were tested for their capacity to support the cell growth, the reinfusion of autologous marrow can recon- growth of allogeneic hematopoietic progenitors. Seven stitute the hematopoietic system, even in acute myelogen- samples failed to support any progenitor cell growth, ous leukemia (AML) patients treated with remission induc- seven had a significantly lower supportive activity as tion regimens exerting a significant marrow toxicity.9,10 compared to normal stromal layers (13 ± 5 vs 249 ± 56, Recently, therapeutic trials have been conducted in AML P < 0.002), whereas three cultures could not be ana- patients which were aimed at evaluating the efficacy of lyzed due to contamination. In conclusion, induction induction and consolidation regimens containing new anti- and consolidation regimens used in AML patients of the leukemic drugs, such as idarubicin or mitoxantrone.11 AML AML10 protocol induce a markedly defective in vitro patients included in the AML10 GIMEMA/EORTC pilot growth of primitive hematopoietic progenitors and a study receiving idarubicin, cytosine arabinoside, and etopo- severe functional defect of marrow stroma. The associ- side (ICE) as induction therapy and mitoxantrone and cyto- ation of hematopoietic with microenvironmental dam- sine arabinoside (NOVIA) as consolidation therapy, have age might play a key role in the delayed hematopoietic been reported to have reduced marrow cellularity, often regeneration observed following ABMT in patients of preventing marrow harvest and dramatically reducing the the AML10 trial. feasibility of autologous bone marrow transplantation (ABMT).12,13 In addition, as compared to historical controls treated with the conventional daunorubicin and cytosine 14 Correspondence: Dr C Carlo-Stella, Cattedra di Ematologia, Universita` di arabinoside (D3A7) protocol, patients autografted with Parma, Via Gramsci, 14, I-43100 Parma, Italy marrow harvested following the ICE/NOVIA regimens, Received 21 February 1997; accepted 26 May 1997 have experienced a significantly prolonged pancytopenia Bone marrow damage after chemotherapy for AML C Carlo-Stella et al 466 associated with increased transplant-related mortality. apy or at marrow harvest, respectively. Normal values for Reduced marrow cellularity and poor graft function were bone marrow progenitor cell growth were provided from also observed in patients included in the AML10 57 healthy subjects (38 males, 19 females) with a median randomized trial who received the same intercalating drug age of 42 years (range, 20–67). (idarubicin, mitoxantrone or daunorubicin) during remission induction and consolidation therapy.13 These Cell separation procedures clinical findings prompted us to hypothesize that adminis- tration of chemotherapy regimens of the AML10 protocols After informed consent was given, bone marrow was could result in severe toxic effects involving both hemato- obtained by aspiration from the posterior iliac crest and poietic and microenvironmental progenitor cell compart- mononuclear cells (MNC) were separated by centrifugation ments. (400 g, 30 min, 4°C) on a Ficoll–Hypaque gradient (density It was, therefore, the aim of the present study to investi- = 1.077 g/ml). Interface cells were washed and suspended gate marrow hematopoietic and microenvironmental pro- in RPMI-1640 (Gibco, Grand Island, NY, USA) sup- genitors in AML patients of the AML10 pilot or ran- plemented with 20% fetal bovine serum (FBS; Hyclone, domized trials. Hematopoietic progenitors were studied by Logan, UT, USA). means of a short-term methylcellulose assay allowing us to quantitate multipotent (CFU-Mix), erythroid (BFU-E) and CFU-Mix, BFU-E and CFU-GM assay granulocyte–macrophage (CFU-GM) progenitors as well as a long-term assay which allows us to quantitate primitive The assay for multilineage colony-forming units (CFU- progenitors capable of initiating and sustaining hematopo- Mix), erythroid bursts (BFU-E), and granulocyte– iesis in long-term culture (long-term culture initiating cells, macrophage colony-forming units (CFU-GM) was carried LTC-IC).15 The marrow microenvironment was studied by out as described elsewhere.18 Briefly, 5 × 104 MNC were quantitating marrow fibroblast colony-forming cells (CFU- plated in 35-mm Petri dishes in 1-ml aliquots of Iscove’s F) and by evaluating the capacity of stromal layers to modified Dulbecco’s medium (IMDM; Seromed, Berlin, support the growth of allogeneic normal hematopoietic Germany) containing: 30% FBS (Stem Cell Technologies, progenitors.16 Vancouver, Canada); 10−4 m 2-mercaptoethanol (Gibco), and 1.1% (w/v) methylcellulose. Cultures were stimulated with interleukin-3 (10 ng/ml; Sandoz, Basel, Switzerland), Materials and methods granulocyte colony-stimulating factor (10 ng/ml, Amgen, Thousand Oaks, CA, USA), granulocyte–macrophage Patients colony-stimulating factor (10 ng/ml; Sandoz) and erythro- poietin (3 U/ml; Amgen). Progenitor cell growth was evalu- ° Twenty-six patients (12 males, 14 females) with a median ated after incubation (37 C, 5% CO2) for 14–18 days in a age of 45 years (range, 14 to 59) and a diagnosis of AML humidified atmosphere. Four dishes were set up for each were included in this study. The diagnosis of AML was individual data point per experiment. CFU-Mix defined as based on the criteria of the French–American–British containing at least erythroid and granulocytic cells, BFU- (FAB) Cooperative Group.17 The study population included E with >500 cells and CFU-GM with >40 cells were patients with different FAB subtypes (M1 (n = 3), M2 (n scored from the same dish. = 9), M4 (n = 8), M5 (n = 5), and M6 (n = 1)). All patients had been treated at the Department of Hematology, ‘La Long-term culture-initiating cell (LTC-IC) assay Sapienza’ University, Rome, according to different remission induction and consolidation protocols. Nine The long-term culture-initiating cell (LTC-IC) assay was patients enrolled in the AML10 GIMEMA/EORTC pilot performed according to a previously described tech- study received the ICE (idarubicin, cytosine arabinoside, nique.15,19 Briefly, MNC were resuspended in complete etoposide) regimen as remission induction therapy and the medium consisting of alpha-medium (Gibco) supplemented NOVIA (mitoxantrone, cytosine arabinoside) regimen as with fetal bovine serum (12.5%), horse serum (12.5%), l- consolidation therapy, whereas the remaining 17 patients glutamine (4 mm), 2-mercaptoethanol
Recommended publications
  • Updates in Mastocytosis
    Updates in Mastocytosis Tryptase PD-L1 Tracy I. George, M.D. Professor of Pathology 1 Disclosure: Tracy George, M.D. Research Support / Grants None Stock/Equity (any amount) None Consulting Blueprint Medicines Novartis Employment ARUP Laboratories Speakers Bureau / Honoraria None Other None Outline • Classification • Advanced mastocytosis • A case report • Clinical trials • Other potential therapies Outline • Classification • Advanced mastocytosis • A case report • Clinical trials • Other potential therapies Mastocytosis symposium and consensus meeting on classification and diagnostic criteria for mastocytosis Boston, October 25-28, 2012 2008 WHO Classification Scheme for Myeloid Neoplasms Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Atypical Chronic Myeloid Leukemia Juvenile Myelomonocytic Leukemia Myelodysplastic Syndromes MDS/MPN, unclassifiable Chronic Myelogenous Leukemia MDS/MPN Polycythemia Vera Essential Thrombocythemia Primary Myelofibrosis Myeloproliferative Neoplasms Chronic Neutrophilic Leukemia Chronic Eosinophilic Leukemia, NOS Hypereosinophilic Syndrome Mast Cell Disease MPNs, unclassifiable Myeloid or lymphoid neoplasms Myeloid neoplasms associated with PDGFRA rearrangement associated with eosinophilia and Myeloid neoplasms associated with PDGFRB abnormalities of PDGFRA, rearrangement PDGFRB, or FGFR1 Myeloid neoplasms associated with FGFR1 rearrangement (EMS) 2017 WHO Classification Scheme for Myeloid Neoplasms Chronic Myelomonocytic Leukemia Acute Myeloid Leukemia Atypical Chronic Myeloid Leukemia Juvenile Myelomonocytic
    [Show full text]
  • Mirna182 Regulates Percentage of Myeloid and Erythroid Cells in Chronic Myeloid Leukemia
    Citation: Cell Death and Disease (2017) 8, e2547; doi:10.1038/cddis.2016.471 OPEN Official journal of the Cell Death Differentiation Association www.nature.com/cddis MiRNA182 regulates percentage of myeloid and erythroid cells in chronic myeloid leukemia Deepak Arya1,2, Sasikala P Sachithanandan1, Cecil Ross3, Dasaradhi Palakodeti4, Shang Li5 and Sudhir Krishna*,1 The deregulation of lineage control programs is often associated with the progression of haematological malignancies. The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia (CML). To find a potential molecular regulator contributing to lineage distribution and TKI resistance, we undertook an RNA-sequencing approach for identifying microRNAs (miRNAs). Following an unbiased screen, elevated miRNA182-5p levels were detected in Bcr-Abl-inhibited K562 cells (CML blast crisis cell line) and in a panel of CML patients. Earlier, miRNA182-5p upregulation was reported in several solid tumours and haematological malignancies. We undertook a strategy involving transient modulation and CRISPR/Cas9 (clustered regularly interspersed short palindromic repeats)-mediated knockout of the MIR182 locus in CML cells. The lineage contribution was assessed by methylcellulose colony formation assay. The transient modulation of miRNA182-5p revealed a biased phenotype. Strikingly, Δ182 cells (homozygous deletion of MIR182 locus) produced a marked shift in lineage distribution. The phenotype was rescued by ectopic expression of miRNA182-5p in Δ182 cells. A bioinformatic analysis and Hes1 modulation data suggested that Hes1 could be a putative target of miRNA182-5p. A reciprocal relationship between miRNA182-5p and Hes1 was seen in the context of TK inhibition.
    [Show full text]
  • Mutations and Prognosis in Primary Myelofibrosis
    Leukemia (2013) 27, 1861–1869 & 2013 Macmillan Publishers Limited All rights reserved 0887-6924/13 www.nature.com/leu ORIGINAL ARTICLE Mutations and prognosis in primary myelofibrosis AM Vannucchi1, TL Lasho2, P Guglielmelli1, F Biamonte1, A Pardanani2, A Pereira3, C Finke2, J Score4, N Gangat2, C Mannarelli1, RP Ketterling5, G Rotunno1, RA Knudson5, MC Susini1, RR Laborde5, A Spolverini1, A Pancrazzi1, L Pieri1, R Manfredini6, E Tagliafico7, R Zini6, A Jones4, K Zoi8, A Reiter9, A Duncombe10, D Pietra11, E Rumi11, F Cervantes12, G Barosi13, M Cazzola11, NCP Cross4 and A Tefferi2 Patient outcome in primary myelofibrosis (PMF) is significantly influenced by karyotype. We studied 879 PMF patients to determine the individual and combinatorial prognostic relevance of somatic mutations. Analysis was performed in 483 European patients and the seminal observations were validated in 396 Mayo Clinic patients. Samples from the European cohort, collected at time of diagnosis, were analyzed for mutations in ASXL1, SRSF2, EZH2, TET2, DNMT3A, CBL, IDH1, IDH2, MPL and JAK2. Of these, ASXL1, SRSF2 and EZH2 mutations inter-independently predicted shortened survival. However, only ASXL1 mutations (HR: 2.02; Po0.001) remained significant in the context of the International Prognostic Scoring System (IPSS). These observations were validated in the Mayo Clinic cohort where mutation and survival analyses were performed from time of referral. ASXL1, SRSF2 and EZH2 mutations were independently associated with poor survival, but only ASXL1 mutations held their prognostic relevance (HR: 1.4; P ¼ 0.04) independent of the Dynamic IPSS (DIPSS)-plus model, which incorporates cytogenetic risk. In the European cohort, leukemia-free survival was negatively affected by IDH1/2, SRSF2 and ASXL1 mutations and in the Mayo cohort by IDH1 and SRSF2 mutations.
    [Show full text]
  • The AML Guide Information for Patients and Caregivers Acute Myeloid Leukemia
    The AML Guide Information for Patients and Caregivers Acute Myeloid Leukemia Emily, AML survivor Revised 2012 Inside Front Cover A Message from Louis J. DeGennaro, PhD President and CEO of The Leukemia & Lymphoma Society The Leukemia & Lymphoma Society (LLS) wants to bring you the most up-to-date blood cancer information. We know how important it is for you to understand your treatment and support options. With this knowledge, you can work with members of your healthcare team to move forward with the hope of remission and recovery. Our vision is that one day most people who have been diagnosed with acute myeloid leukemia (AML) will be cured or will be able to manage their disease and have a good quality of life. We hope that the information in this Guide will help you along your journey. LLS is the world’s largest voluntary health organization dedicated to funding blood cancer research, advocacy and patient services. Since the first funding in 1954, LLS has invested more than $814 million in research specifically targeting blood cancers. We will continue to invest in research for cures and in programs and services that improve the quality of life for people who have AML and their families. We wish you well. Louis J. DeGennaro, PhD President and Chief Executive Officer The Leukemia & Lymphoma Society Inside This Guide 2 Introduction 3 Here to Help 6 Part 1—Understanding AML About Marrow, Blood and Blood Cells About AML Diagnosis Types of AML 11 Part 2—Treatment Choosing a Specialist Ask Your Doctor Treatment Planning About AML Treatments Relapsed or Refractory AML Stem Cell Transplantation Acute Promyelocytic Leukemia (APL) Treatment Acute Monocytic Leukemia Treatment AML Treatment in Children AML Treatment in Older Patients 24 Part 3—About Clinical Trials 25 Part 4—Side Effects and Follow-Up Care Side Effects of AML Treatment Long-Term and Late Effects Follow-up Care Tracking Your AML Tests 30 Take Care of Yourself 31 Medical Terms This LLS Guide about AML is for information only.
    [Show full text]
  • Myelodysplastic Syndromes Overview and Types
    cancer.org | 1.800.227.2345 About Myelodysplastic Syndromes Overview and Types If you have been diagnosed with a myelodysplastic syndrome or are worried about it, you likely have a lot of questions. Learning some basics is a good place to start. ● What Are Myelodysplastic Syndromes? ● Types of Myelodysplastic Syndromes Research and Statistics See the latest estimates for new cases of myelodysplastic syndromes in the US and what research is currently being done. ● Key Statistics for Myelodysplastic Syndromes ● What's New in Myelodysplastic Syndrome Research? What Are Myelodysplastic Syndromes? Myelodysplastic syndromes (MDS) are conditions that can occur when the blood- forming cells in the bone marrow become abnormal. This leads to low numbers of one or more types of blood cells. MDS is considered a type of cancer1. Normal bone marrow 1 ____________________________________________________________________________________American Cancer Society cancer.org | 1.800.227.2345 Bone marrow is found in the middle of certain bones. It is made up of blood-forming cells, fat cells, and supporting tissues. A small fraction of the blood-forming cells are blood stem cells. Stem cells are needed to make new blood cells. There are 3 main types of blood cells: red blood cells, white blood cells, and platelets. Red blood cells pick up oxygen in the lungs and carry it to the rest of the body. These cells also bring carbon dioxide back to the lungs. Having too few red blood cells is called anemia. It can make a person feel tired and weak and look pale. Severe anemia can cause shortness of breath. White blood cells (also known as leukocytes) are important in defending the body against infection.
    [Show full text]
  • Chronic Myeloid Leukemia Mimicking Primary Myelofibrosis: a Case Report
    ISSN: 2640-7914 DOI: https://dx.doi.org/10.17352/ahcrr CLINICAL GROUP Received: 02 November, 2020 Case Report Accepted: 01 February, 2021 Published: 02 February, 2021 *Corresponding author: Anju S, Junior Resident, Gov- Chronic myeloid leukemia ernment Medical College, Kottayam, Kerala, India, Tel: 91 9496057350; E-mail: mimicking primary Keywords: Chronic myeloid leukemia; Primary myelo- fi brosis; Blast crisis; Myeloproliferative neoplasms myelofi brosis: A case report https://www.peertechz.com Anju S*, Jayalakshmy PL and Sankar Sundaram Junior Resident, Government Medical College, Kottayam, Kerala, India Abstract Bone marrow fi brosis leading to dry tap aspiration and often associated with blast crisis has previously been reported in both Chronic myeloid leukemia and Primary myelofi brosis. The similarities between these two conditions in terms of clinical presentation and morphology can really create a diagnostic dilemma. Here we present a case of Chronic myeloid leukemia in fi brosis and blast crisis in a 32 year old lady which closely resembled Primary myelofi brosis in transformation. All myeloproliferative neoplasms can undergo blast transformation. In this case, the detection of Philadelphia chromosome helped to distinguish Chronic myeloid leukemia from other myeloproliferative neoplasms. Introduction diffi cult to distinguish the different MPNs especially those in blast crisis and fi brosis. The treatment of CML involves targeted Myeloproliferative Neoplasm (MPN) results from therapy namely, Imatinib mesylate, which is a tyrosine kinase unchecked proliferation of the cellular elements in the bone inhibitor. Also, JAK1/2 inhibitors administered in PMF patients marrow characterized by panmyelosis and accompanied by show clinical improvement [2]. So, it is Important to distinguish erythrocytosis, granulocytosis, and/or thrombocytosis in every MPNs even in their blastic phase as they have different the peripheral blood.
    [Show full text]
  • Chronic Myeloid Leukemia: a Guide for Patients
    Chronic Myeloid Leukaemia What is chronic myeloid leukaemia? Let us explain it to you. www.anticancerfund.org www.esmo.org ESMO/ACF Patient Guide Series based on the ESMO Clinical Practice Guidelines CHRONIC MYELOID LEUKEMIA: A GUIDE FOR PATIENTS PATIENT INFORMATION BASED ON ESMO CLINICAL PRACTICE GUIDELINES This guide for patients has been prepared by the Anticancer Fund as a service to patients, to help patients and their relatives better understand the nature of Chronic Myeloid Leukemia (CML) and appreciate the best treatment choices available according to the subtype of CML. We recommend that patients talk to their doctors about the tests or treatments that are needed for their type and stage of disease. The medical information described in this document is based on the clinical practice guidelines of the European Society for Medical Oncology (ESMO) for the management of Chronic Myeloid Leukemia. This guide for patients has been produced in collaboration with ESMO and is disseminated with the permission of ESMO. It has been written by a medical doctor and reviewed by two oncologists from ESMO including the lead author of the clinical practice guidelines for professionals. It has also been reviewed by patients’ representatives from ESMO’s Cancer Patient Working Group. More information about the Anticancer Fund: www.anticancerfund.org More information about the European Society for Medical Oncology: www.esmo.org For words marked with an asterisk, a definition is provided at the end of the document. CML: a guide for patients - Information based on ESMO Clinical Practice Guidelines - v.2013.1 Page 1 This document is provided by the Anticancer Fund with the permission of ESMO.
    [Show full text]
  • Acute Erythroid Leukemia: a Review
    110 Apr 2012 Vol 5 No.2 North American Journal of Medicine and Science Review Acute Erythroid Leukemia: A Review Daniela Mihova, MD, FCAP;1* Lanjing Zhang, MD, MS, FCAP2,3 1 Pathology Department and Clinical Laboratories, Flushing Hospital Medical Center, Flushing, NY 2 Department of Pathology, University Medical Center at Princeton, Princeton, NJ 3 Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School-UMDNJ, New Brunswick, NJ Acute erythroid leukemia is a rare form of acute myeloid leukemia. It accounts for <5% of all acute myeloid leukemia cases. According to the World Health Organization 2008 classification, it falls under the category of acute myeloid leukemia, not otherwise specified and is further divided into two subtypes: erythroid leukemia (erythroid/myeloid) and pure erythroid leukemia. Currently, erythroleukemia (erythroid/myeloid) is defined as 50% or more erythroid precursors and ≥20% blasts of the non-erythroid cells. By definition, pure erythroid leukemia is composed of ≥80% erythroid precursors. Acute erythroid leukemia is a diagnosis of exclusion and difficulty. This review discusses its differential diagnoses, which present with erythroid proliferation, such as myelodysplastic syndrome with erythroid proliferation, acute myeloid leukemia with myelodysplasia related changes, therapy related acute myeloid leukemia, myeloproliferative neoplasms with erythroblast transformation, acute myeloid leukemia with recurrent genetic abnormalities and other types of hematologic neoplasms. Additionally, reactive conditions such as erythropoietin treatment, vitamin B12 and folate deficiency, toxin exposure and congenital dyserythropoiesis should be excluded. As a result, the frequency of acute erythroid leukemia diagnosis has been reduced. Important adverse prognostic factors will be summarized, including presence of complex cytogenetic karyotype as the most important one.
    [Show full text]
  • Treating Acute Myeloid Leukemia (AML) If You've Been Diagnosed with Acute Myeloid Leukemia (AML), Your Cancer Care Team Will Discuss Your Treatment Options with You
    cancer.org | 1.800.227.2345 Treating Acute Myeloid Leukemia (AML) If you've been diagnosed with acute myeloid leukemia (AML), your cancer care team will discuss your treatment options with you. Your options may be affected by the AML subtype, as well as certain other prognostic factors, as well as your age and overall state of health. How is acute myeloid leukemia treated? The main treatment for most types of AML is chemotherapy, sometimes along with a targeted therapy drug. This might be followed by a stem cell transplant. Other drugs (besides standard chemotherapy drugs) may be used to treat people with acute promyelocytic leukemia (APL). Surgery and radiation therapy are not major treatments for AML, but they may be used in special circumstances. ● Chemotherapy for Acute Myeloid Leukemia (AML) ● Targeted Therapy Drugs for Acute Myeloid Leukemia (AML) ● Non-Chemo Drugs for Acute Promyelocytic Leukemia (APL) ● Surgery for Acute Myeloid Leukemia (AML) ● Radiation Therapy for Acute Myeloid Leukemia (AML) ● Stem Cell Transplant for Acute Myeloid Leukemia (AML) Common treatment approaches The typical treatment approach for AML is different from the treatment approach for acute promyelocytic leukemia (APL). The response rates for treatment can vary based on the subtype of AML, as well as other factors. Treatment options might be different if the AML doesn't respond to the initial treatment or if it comes back later on. The treatment approach for children with AML can be slightly different from that used for adults. It's discussed separately in Treatment of Children With Acute Myeloid Leukemia 1 ____________________________________________________________________________________American Cancer Society cancer.org | 1.800.227.2345 (AML).
    [Show full text]
  • SRC-Family Kinases in Acute Myeloid Leukaemia and Mastocytosis
    cancers Review SRC-Family Kinases in Acute Myeloid Leukaemia and Mastocytosis Edwige Voisset , Fabienne Brenet , Sophie Lopez and Paulo de Sepulveda * INSERM U1068, CNRS UMR7258, Aix-Marseille Université UM105, Institute Paoli-Calmettes, CRCM—Cancer Research Center of Marseille, U1068 Marseille, France; [email protected] (E.V.); [email protected] (F.B.); [email protected] (S.L.) * Correspondence: [email protected] Received: 28 May 2020; Accepted: 19 July 2020; Published: 21 July 2020 Abstract: Protein tyrosine kinases have been recognized as important actors of cell transformation and cancer progression, since their discovery as products of viral oncogenes. SRC-family kinases (SFKs) play crucial roles in normal hematopoiesis. Not surprisingly, they are hyperactivated and are essential for membrane receptor downstream signaling in hematological malignancies such as acute myeloid leukemia (AML) and mastocytosis. The precise roles of SFKs are difficult to delineate due to the number of substrates, the functional redundancy among members, and the use of tools that are not selective. Yet, a large num ber of studies have accumulated evidence to support that SFKs are rational therapeutic targets in AML and mastocytosis. These two pathologies are regulated by two related receptor tyrosine kinases, which are well known in the field of hematology: FLT3 and KIT. FLT3 is one of the most frequently mutated genes in AML, while KIT oncogenic mutations occur in 80–90% of mastocytosis. Studies on oncogenic FLT3 and KIT signaling have shed light on specific roles for members of the SFK family. This review highlights the central roles of SFKs in AML and mastocytosis, and their interconnection with FLT3 and KIT oncoproteins.
    [Show full text]
  • Preferential Eradication of Acute Myelogenous Leukemia Stem Cells by Fenretinide
    Preferential eradication of acute myelogenous leukemia stem cells by fenretinide Hui Zhanga,1, Jian-Qing Mia,1, Hai Fanga,b,1, Zhao Wanga,1, Chun Wangc, Lin Wua,c, Bin Zhanga, Mark Mindend, Wen-Tao Yanga, Huan-Wei Wanga, Jun-Min Lia, Xiao-Dong Xia, Sai-Juan Chena, Ji Zhanga,b,e,2, Zhu Chena,e,2, and Kan-Kan Wanga,e,2 aState Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU- SM), Shanghai 200025, China; bInstitute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and SJTU-SM, Shanghai 200025, China; cThe First People Hospital, Shanghai Jiao Tong University, Shanghai 200080, China; dPrincess Margaret Hospital/Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2M9; and eSamuel Waxman Cancer Research Foundation Laboratory, Shanghai Ruijin Hospital, Shanghai 200025, China Contributed by Zhu Chen, February 8, 2013 (sent for review November 14, 2012) Leukemia stem cells (LSCs) play important roles in leukemia activation of nuclear factor κB (NF-κB), active Wnt/β-catenin initiation, progression, and relapse, and thus represent a critical signaling, and elevated levels of interferon regulatory factor-1 target for therapeutic intervention. However, relatively few (IRF-1) and death-associated protein kinase (DAPK) (8–12). agents have been shown to target LSCs, slowing progress in the Most recently, emerging evidence points to oxidative signaling as treatment of acute myelogenous leukemia (AML). Based on in being a two-edged sword in AML: moderate levels of reactive vitro and in vivo evidence, we report here that fenretinide, a well- oxygen species (ROS) are important for driving disease, whereas tolerated vitamin A derivative, is capable of eradicating LSCs higher levels result in cell death (13–15).
    [Show full text]
  • Myelodysplastic Syndrome Early Detection, Diagnosis, and Staging Detection and Diagnosis
    cancer.org | 1.800.227.2345 Myelodysplastic Syndrome Early Detection, Diagnosis, and Staging Detection and Diagnosis Catching cancer early often allows for more treatment options. Some early cancers may have signs and symptoms that can be noticed, but that is not always the case. ● Can Myelodysplastic Syndromes Be Found Early? ● Signs and Symptoms of Myelodysplastic Syndromes ● Tests for Myelodysplastic Syndromes MDS Scores and Prognosis (Outlook) Myelodysplastic syndrome scores provide important information about the anticipated response to treatment. ● Myelodysplastic Syndrome Prognostic Scores ● Survival Statistics for Myelodysplastic Syndromes Questions to Ask About Myelodysplastic Syndromes Here are some questions you can ask your cancer care team to help you better understand your diagnosis and treatment options. ● Questions to Ask Your Doctor About Myelodysplastic Syndromes 1 ____________________________________________________________________________________American Cancer Society cancer.org | 1.800.227.2345 Can Myelodysplastic Syndromes Be Found Early? At this time, there are no widely recommended tests to screen for myelodysplastic syndromes (MDS). (Screening is testing for cancer in people without any symptoms.) MDS is sometimes found when a person sees a doctor because of signs or symptoms they are having. These signs and symptoms often do not show up in the early stages of MDS. But sometimes MDS is found before it causes symptoms because of an abnormal result on a blood test that was done as part of a routine exam or for some other health reason. MDS that is found early does not always need to be treated right away, but it should be watched closely for signs that it's progressing. For some people who are known to be at increased risk1, such as people with certain inherited syndromes or people who have received certain chemotherapy drugs, doctors might recommend close follow-up with blood tests or other exams or tests to look for possible early signs of MDS.
    [Show full text]