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Acute Leukemia News Headlines
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All Recent Acute Leukemia News Headlines |
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Acute Myelogenous Leukemia
Genetics, Biology and Therapyseries:Cancer Treatment and ResearchAcute myelogenous leukemia (AML), is the most common form of leukemia in adults. AML is a deadly form of malignancy, the prognosis for which has not improved in the last two decades. More importantly, it is a malignancy that is seen in older adults, therefore the number of cases is likely to rise as the population ages. Over the past 15 years, genetic mechanisms underlying AML have begun to ... (Source: Springer Medicine titles)...
POSTED 03/09/2010 at 08:03 AM --
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Targeting leukemia stem cells
Authors: Hanna K A Mikkola, Caius G Radu & Owen N Witte
Acute myeloid leukemia stem cells can be made susceptible to chemotherapy by inducing them to divide. (Source: Nature Biotechnology)...
POSTED 03/08/2010 at 11:42 AM --
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Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies
Conclusions:
This study demonstrates, for the first time, that the expression profiles of childhood leukemia are largely unique, with limited similarities to transcriptional programs active in normal hematopoietic cells, non-hematopoietic normal tissues or the most common forms of human cancer. In addition to providing important pathogenetic insights, these findings should facilitate the identification of candidate genes or transcriptional programs that can be used as unique targets in leukemia. (Source: BMC Medical Genomics)...
POSTED 03/07/2010 at 06:00 PM --
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Favourable outcome of patients with childhood acute promyelocytic leukaemia after treatment with reduced cumulative anthracycline doses
Acute promyelocytic leukaemia (APL) treatment often includes high cumulative doses of anthracyclines, which can cause long-term cardiotoxicity. Here, we report the favourable outcome in 81 paediatric APL patients treated according to the consecutive acute myeloid leukaemia-Berlin/Frankfurt/Muenster (AML-BFM) trials -93/-98/-2004 with an anthracycline-cytarabine regimen in combination with all-trans-retinoid acid (ATRA). Outcomes achieved by treatment with a reduced cumulative anthracycline dose (350 mg/m2) were comparable to those reported for studies with higher doses. Five-year overall survival of the total cohort was 89 ± 4% and event-free survival (pEFS) was 73 ± 6%. Overall survival was similar when comparing AML-BFM trial periods (trial 93: 88 ± 8%, 98: 85 ± 7% and 2004: 94 ± 8%......
POSTED 03/07/2010 at 06:00 PM --
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Mitochondrial D-loop variations in paediatric acute myeloid leukaemia: a potential prognostic marker
In conclusion, this is the largest study to show a high frequency of mtDNA variations in paediatric AML and their potential relevance as a prognostic marker in this disease. (Source: British Journal of Haematology)...
POSTED 03/07/2010 at 06:00 PM --
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Phase I trial of ATRA-IV and depakote in patients with advanced solid tumor malignancies.
Authors: David KA, Mongan NP, Smith C, Gudas LJ, Nanus DM
Retinoic acid derivatives have shown their greatest benefit in acute promyelocytic leukemia, but have also demonstrated pre-clinical anti-cancer effects in some solid tumors. Histone deacetylase inhibitors, by upregulating gene expression, are able to limit cancer cell proliferation and induce apoptosis. The combination of all-trans retinoic acid (ATRA) and the histone deacetylase inhibitor valproic acid has been previously studied in hematologic malignancies. We conducted a phase I two-step dose escalation trial of the liposomal ATRA analog ATRA-IV and divalproex sodium (Depakote((R))) in nine patients with advanced solid tumors refractory to prior therapy. Side effects attributed to therapy had a severity </=grade 2 and inc......
POSTED 03/06/2010 at 01:28 PM --
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Featured Article: Therapeutics: Selective inhibitors gain traction
A selective TORC1 and TORC2 active site inhibitor has high efficacy and tolerability in models of acute leukaemia. (Source: Nature Signaling Update)...
POSTED 03/05/2010 at 09:30 AM --
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Intracellular Succinylation of 8-Chloroadenosine and Its Effect on Fumarate Levels [Bioenergetics]
8-Chloroadenosine (8-Cl-Ado) is a ribosyl nucleoside analog currently in phase I testing for the treatment of chronic lymphocytic leukemia (CLL). 8-Cl-Ado activity is dependent on adenosine kinase and requires intracellular accumulation of 8-Cl-Ado as mono-, di-, and tri-phosphates. In the current study with four mantle cell lymphoma cell lines, we report a new major metabolic pathway for 8-Cl-Ado intracellular metabolism, the formation of succinyl-8-chloro-adenosine (S-8-Cl-Ado) and its monophosphate (S-8-Cl-AMP). 8-Cl-AMP levels were highly associated with S-8-Cl-AMP levels and reached a steady-state prior to the secondary metabolites, 8-Cl-ATP and S-8-Cl-Ado. Consistent with fumarate as a required substrate for formation of succinyl-8-Cl-adenylate metabolites, the S-8-Cl-adenylate conce......
POSTED 03/05/2010 at 08:37 AM --
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Characteristics of pericardial effusions in patients with leukemia
Little information exists regarding the prevalence and natural history of pericardial disease in patients with leukemia. Recently, it has been reported that the use of histone deacetylase inhibitors is associated with an increased incidence of pericardial effusions (PEs). To study the characteristics and treatment relationships of PEs in patients with leukemia, the authors retrospectively analyzed a cohort of patients with leukemia evaluated at a single center.The authors reviewed 2592 patients with acute myeloid leukemia (AML, n = 1282, 49%), acute lymphocytic leukemia (ALL, n = 336, 13%), or myelodysplastic syndrome (MDS, n = 974, 38%), who were evaluated from August 2003 to July 2008. Electronic medical records were reviewed to select patients who had undergone at least 1 echocardiograp......
POSTED 03/04/2010 at 06:00 PM --
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Central nervous system prophylaxis in adults with acute lymphoblastic leukemia
Central nervous system (CNS) recurrence continues to be a significant complication in the treatment of adult patients with acute lymphoblastic leukemia (ALL). Preventing CNS recurrence has been a therapeutic challenge and has not been addressed critically in many clinical trials. Adult studies modeled on childhood ALL studies have used multiple treatment modalities, including radiation therapy, systemic therapy, intrathecal therapy, and combinations thereof. Cranial irradiation is effective but is offset by substantial toxicity, including neurologic sequelae. Systemic chemotherapy, especially with cytarabine (AraC) and methotrexate, has demonstrated promise in decreasing CNS recurrence, but therapeutic levels of drugs in the cerebrospinal fluid (CSF) are not maintained. Intrathecal chemoth......
POSTED 03/04/2010 at 06:00 PM --
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Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood
Recent genome-wide association data have implicated genetic variation at 7p12.2 (IKZF1), 10q21.2 (ARIDB5), and 14q11.2 (CEBPE) in the etiology of B-cell childhood acute lymphoblastic leukemia (ALL). To verify and further examine the relationship between these variants and ALL risk, we genotyped 1384 cases of precursor B-cell childhood ALL and 1877 controls from Germany and the United Kingdom. The combined data provided statistically significant support for an association between genotype at each of these loci and ALL risk; odds ratios (OR), 1.69 (P = 7.51 x10–22), 1.80 (P = 5.90 x 10–28), and 1.27 (P = 4.90 x 10–6), respectively. Furthermore, the risk of ALL increases with an increasing numbers of variant alleles for the 3 loci (ORper-allele = 1.53, 95% confidence interva......
POSTED 03/04/2010 at 11:00 AM --
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Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia
In this report, we demonstrate that during granulopoiesis microRNA-223 targets E2F1. E2F1 protein was up-regulated in miR-223 null mice. We show that miR-223 blocks cell-cycle progression in myeloid cells. miR-223 is down-regulated in different subtypes of acute myeloid leukemia (AML). We further show that E2F1 binds to the miR-223 promoter in AML blast cells and inhibits miR-223 transcription, suggesting that E2F1 is a transcriptional repressor of the miR-223 gene in AML. Our study supports a molecular network involving miR-223, C/EBP, and E2F1 as major components of the granulocyte differentiation program, which is deregulated in AML. (Source: Blood)...
POSTED 03/04/2010 at 11:00 AM --
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Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience
This study is registered at http://clinicaltrials.gov as NCT00599937. (Source: Blood)...
POSTED 03/04/2010 at 11:00 AM --
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Single-agent arsenic trioxide in the treatment of children with newly diagnosed acute promyelocytic leukemia
The aim of this study was to determine the efficacy and safety of treatment of pediatric acute promyelocytic leukemia (APL) with single-agent arsenic trioxide (ATO). A total of 19 children (≤ 15 years of age) with newly diagnosed APL were treated with single-agent ATO for remission induction and postremission therapy. Seventeen of the children (89.5%) achieved complete hematologic remission, and 2 early deaths occurred from intracranial hemorrhage. ATO-induced leukocytosis was observed in 13 (68.4%) patients. Other ATO-related toxicities were minimal and transient. Postremission ATO therapy continued for 3 years; the most common side effect was ATO-induced neutropenia. With a median follow-up of 53 months (range, 23-76 months), the calculated 5-year overall survival and event-free survi......
POSTED 03/04/2010 at 11:00 AM --
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Interconnecting molecular pathways in the pathogenesis and drug sensitivity of T-cell acute lymphoblastic leukemia
To identify dysregulated pathways in distinct phases of NOTCH1-mediated T-cell leukemogenesis, as well as small-molecule inhibitors that could synergize with or substitute for -secretase inhibitors (GSIs) in T-cell acute lymphoblastic leukemia (T-ALL) therapy, we compared gene expression profiles in a Notch1-induced mouse model of T-ALL with those in human T-ALL. The overall patterns of NOTCH1-mediated gene expression in human and mouse T-ALLs were remarkably similar, as defined early in transformation in the mouse by the regulation of MYC and its target genes and activation of nuclear factor-B and PI3K/AKT pathways. Later events in murine Notch1-mediated leukemogenesis included down-regulation of genes encoding tumor suppressors and negative cell cycle regulators. Gene set enrichment anal......
POSTED 03/04/2010 at 11:00 AM --
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Pharmacological activation of the p53 pathway in haematological malignancies
p53 gene mutations are rarely detected at diagnosis in common haematological cancers such as multiple myeloma (MM), acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL) and Hodgkin's disease (HD), although their prevalence may increase with progression to more aggressive or advanced stages. Therapeutic induction of p53 might therefore be particularly suitable for the treatment of haematological malignancies. Some of the anti-tumour activity of current chemotherapeutics has been derived from activation of p53. However, until recently it was unknown whether p53 signalling is functional in certain haematological cancers including MM and if p53 activity is sufficient to trigger an apoptotic response. With the recent discovery of nutlins, which represent the first highly selective......
POSTED 03/04/2010 at 09:42 AM --
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Targeting Leukaemia Cell's Gene 'addiction' Presents New Strategy For Treatment
An international team of scientists studying acute forms of Leukaemia have identified a new drug target to inhibit the genes which are vital for the growth of diseased cells. The research, reported in EMBO Molecular Medicine, reveals how leukaemia cells become 'addicted' to genes, which if targeted could prevent diseased cells from developing... (Source: Genetics News From Medical News Today)...
POSTED 03/04/2010 at 06:00 AM --
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Targeting PKCδ-mediated topoisomerase IIβ overexpression subverts the differentiation block in a retinoic acid-resistant APL cell line
Targeting PKCδ-mediated topoisomerase IIβ overexpression subverts the differentiation block in a retinoic acid-resistant APL cell line
Leukemia advance online publication, March 4, 2010. doi:10.1038/leu.2010.27
Authors: S McNamara, J N Nichol, H Wang
& W H Miller (Source: Leukemia)...
POSTED 03/03/2010 at 06:00 PM --
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Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms
Authors: A M Martelli, V Papa, P L Tazzari, F Ricci, C Evangelisti, F Chiarini, C Grimaldi, A Cappellini, G Martinelli, E Ottaviani, P Pagliaro, S Horn, J Bäsecke, L H Lindner, H Eibl
& J A McCubrey (Source: Leukemia)...
POSTED 03/03/2010 at 06:00 PM --
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Epidemiology of paediatric invasive fungal infections and a case-control study of risk factors in acute leukaemia or post stem cell transplant
Hale KA, Shaw PJ, Dalla-Pozza L, Macintyre CR, Isaacs D, Sorrell TC (Source: The Aspergillus Website - articles)...
POSTED 03/03/2010 at 06:00 PM --
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