ABSTRACT
OBJECTIVES: Patients with near-tetraploid (karyotype: 81 - 103 chromosomes) acute lymphoblastic leukemia (NT-ALL) constitute about 1% of childhood ALL and data reported on them are limited and controversial. The aim of the study was to enlarge the knowledge on these rarely occurring ALL. METHODS: The members of the European Group for Immunophenotyping of Leukemias (EGIL) searched retrospectively their databases for NT-ALL patients. RESULTS: We collected data of 36 European children from seven European countries with NT-ALL diagnosed since 1992. All patients reached complete remission (CR) after induction chemotherapy. Their blasts were negative for peroxidase and BCR-ABL1. Ten children were diagnosed as T-cell ALL (T-ALL) EGIL categories (T-I n=2, T-II n=2, T-III n=3, T-IV n=3) and four displayed various structural chromosomal abnormalities. Eight of 10 T-ALL remained in 1st CR; one died in CR from sepsis and one is alive in 2nd CR. Median survival was 88 (7-213) months. B-cell precursor (BCP) ALL was diagnosed in 26 children. Thirteen were positive for ETV6-RUNX1 and are alive in 1st CR for 32-147 months. Ten children were ETV6-RUNX1 negative and remained in 1st CR for 16-163 months. One girl with hypodiploid and NT metaphases and ETV6-RUNX1-negative BCP-ALL and one of two boys with NT-BCP-ALL not examined for ETV6-RUNX1 died of infection after stem cell transplantation in 2nd/3rd CR. Secondary myelodysplastic syndrome developed in two patients with NT-BCP-ALL. CONCLUSIONS: Our data demonstrate immunophenotypic, cytogenetic, and molecular heterogeneity of NT-ALL and favorable prognosis of most NT-ALL across different immunophenotypic and/or genetic ALL subtypes.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Chromosome Aberrations , Core Binding Factor Alpha 2 Subunit , Europe , Female , Fusion Proteins, bcr-abl/genetics , Humans , Immunophenotyping , Karyotyping , Male , Oncogene Proteins, Fusion/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Remission Induction , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
Indirubin-3'-monoxime (IO) is a derivative of indirubin, an active compound of a traditional Chinese medicinal recipe used to treat various inflammatory and malignant diseases. The main in vitro targets of IO (i.e. cyclin dependent kinases, glycogen synthase kinase-3beta, Stat 3 and Aryl hydrocarbon receptor) are regulators of lymphocyte activation. We investigated the interest of IO and its derivative 6-bromo-indirubin-3'oxime (6BIO) for inhibiting the growth of malignant lymphoid cells. IO (1-20 microM) induced cell cycle inhibition and cell death in malignant B- (IM9, Reh6) and T- (Jurkat, CEM-T) lymphoid cell lines depending to cell type, doses, and duration of treatment. IO and 6BIO (10 microM) treatment for 24 and 48 h were compared: 6BIO treatment resulted in a stronger cytotoxicity and more profound inhibition of cell proliferation. Taken together, these results showed that IO and, moreover, its derivative 6BIO may be potent antiproliferative agents in malignant lymphoid cells.
Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Indoles/pharmacology , Lymphocytes/drug effects , Oximes/pharmacology , Antibiotics, Antineoplastic/pharmacology , Autophagy/drug effects , Blotting, Western , Cell Cycle/drug effects , Cell Cycle Proteins/metabolism , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Cyclin E/metabolism , Cyclin-Dependent Kinase 6/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cyclin-Dependent Kinase Inhibitor p27 , Dose-Response Relationship, Drug , Flow Cytometry , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Jurkat Cells , Lymphocytes/metabolism , Lymphocytes/pathology , Time FactorsABSTRACT
BACKGROUND: To demonstrate that primary human herpesvirus 6 (HHV-6) infection in childhood can cause hematopoietic dysplasia that mimics a myelodysplastic syndrome (MDS) in severe cases. PROCEDURE: Seven immunocompetent children, who presented at admission with concomitant cytopenias in blood and morphologic features of dysplasia in bone marrow, were evaluated. Diagnosis of acute HHV-6 infection was secondary made by detection of HHV-6 DNA in plasma, bone marrow, or cerebrospinal fluid and measurement of plasma antibody titers. Peripheral blood and bone marrow aspirate smears were examined at diagnosis and during follow-up. Morphologic recognition of myelodysplasia was made according to the recommendations of the Third MIC Cooperative Group. RESULTS: Anemia was the most frequent cytopenia (five of seven cases). Bi- or tri-lineage dysplasia was observed in the marrow samples. Granulocytic and erythroid cells were always affected with dysgranulopoiesis and dyserythropoiesis scores equal to or higher than 3. Myelodysplasia was not due to a clonal disorder and disappeared gradually within 1 or 2 months. CONCLUSIONS: Our results indicate that severe HHV-6 infection may induce reversible myelodysplastic changes. These findings contribute to elucidate the pathogenicity of HHV-6 and furthermore suggest that HHV-6 infection must also be considered as a cause of dysplasia in the differential diagnosis of MDS.
Subject(s)
Myelodysplastic Syndromes/diagnosis , Roseolovirus Infections/diagnosis , Acute Disease , Adolescent , Blood Cell Count , Bone Marrow/pathology , Child, Preschool , Comorbidity , Convalescence , Diagnosis, Differential , Female , Follow-Up Studies , France/epidemiology , Herpesvirus 6, Human/isolation & purification , Humans , Infant , Male , Myelodysplastic Syndromes/epidemiology , Myelodysplastic Syndromes/therapy , Retrospective Studies , Roseolovirus Infections/epidemiology , Roseolovirus Infections/therapy , Treatment OutcomeABSTRACT
We report two cases of visceral larva migrans (VLM) syndrome by Toxocara in children. The biological presentation was unusual and characterized by persistent secondary thrombocytosis (>1,000 x 10(9)/L) mimicking an essential thrombocythemia and variable hypereosinophilia syndrome. Both children had non-specific symptoms including abdominal pain, skin rash, and fever. The diagnosis was confirmed by serology. The children were treated with either thiabendazole or albendazole, resulting in normalization of eosinophil and platelet counts.
