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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., (© 2010 John Wiley & Sons A/S.)

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.

Indirubin-3'-monoxime (IO) is a derivative of Indirubin, compound of a Chinese medicinal recipe used to treat various diseases including leukemia. In this study, we investigated to what extent IO inhibits the growth of normal human lymphocytes. We defined various experimental conditions of peripheral blood lymphocyte treatment: IO introduced (i) on unstimulated lymphocytes, (ii) or on stimulated lymphocytes at the time of phytohemagglutinin stimulation (L1 protocol), (iii) 48 h after the beginning of stimulation (L2 protocol), and (iv) after nocodazole synchronization of stimulated lymphocytes. IO induces a concentration dependent cytotoxic effect yielding a characteristic sub-G1 peak in normal stimulated lymphocytes. Cell death was partly due to necrosis and apoptosis. Normal unstimulated lymphocytes remained insensitive to the cytotoxic effect of 10 microM IO treatment. A cell cycle inhibition was observed after IO treatment, stronger for the L1 than for the L2 protocol, without induction of polyploidy after Nocodazole synchronization. These cellular consequences were associated with a decrease in CDK activity, and with CDK and cyclin gene expression modifications. The inhibition of lymphocyte proliferation by IO indicates that indirubin derivatives may be potent immunosuppressive agents.

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., (Copyright (c) 2005 Wiley-Liss, Inc.)

Thrombocytosis is frequently observed in pediatric patients. Among them the secondary thrombocytosis are the most frequent and result from several causes. The rarely primary thrombocytosis can be either constitutive (and often familial) or acquired (essential thrombocythemia). The purpose of this article is to give diagnostic orientation and to suggest which biological tests should be performed.

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.