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Acute Promyelocytic Leukaemia (acute + promyelocytic_leukaemia)

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Medical Sciences	100%

Selected Abstracts

All- Trans Retinoic Acid (Atra) and Tranexamic Acid: A Potentially Fatal Combination In Acute Promyelocytic Leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2000
J. E. Brown
First page of article [source]

Evaluation of PG-M3 antibody in the diagnosis of acute promyelocytic leukaemia

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2010
Sanjeev Kumar Gupta
Eur J Clin Invest 2010; 40 (10): 960,962 Abstract Background & objectives, Acute promyelocytic leukaemia (APL) is a distinct subtype of acute myeloid leukaemia (AML) characterized by a reciprocal translocation, t(15;17) and a high incidence of life-threatening coagulopathy. APL diagnosis is considered a medical emergency. As reverse transcription-polymerase chain reaction (RT-PCR) for PML-RAR, fusion oncoprotein is time consuming, there is a need for a rapid and accurate diagnostic test for APL. This study evaluates the role of PG-M3 monoclonal antibody using immunofluorescence (IF) in the early diagnosis of APL. Materials and Methods, Thirty-six new untreated APL cases diagnosed with RT-PCR for PML-RAR, as the gold standard and 38 non-APL controls (28 non-APL AMLs and 10 non-leukaemic samples) were evaluated by routine morphology and cytochemistry, RT-PCR and IF using PG-M3 monoclonal antibody. Results, Using IF, 34 of 36 (94·4%) APL cases showed a microgranular pattern suggestive of APL and two cases (5·6%) showed a speckled pattern typical of wild-type PML protein (False negative). By comparison, two of 28 (7·1%) non-APL AMLs showed microgranular pattern (false positive). Hence, IF as a diagnostic test for APL resulted in a sensitivity of 94·4%, specificity of 92·9% and positive and negative predictive values of 94·4% and 92·9% respectively. All 10 non-leukaemic samples showed a speckled pattern. Conclusions, IF using PG-M3 antibodies can be used as a rapid (takes 2 h), cheap, sensitive and specific method to identify APL. It can be a useful adjunct for diagnosis of APL especially if facilities for RT-PCR are not available, particularly in resource-limited settings. [source]

Epigallocatechin-3-gallate induces cell death in acute myeloid leukaemia cells and supports all- trans retinoic acid-induced neutrophil differentiation via death-associated protein kinase 2

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2010
Adrian Britschgi
Summary Acute promyelocytic leukaemia (APL) patients are successfully treated with all- trans retinoic acid (ATRA). However, concurrent chemotherapy is still necessary and less toxic therapeutic approaches are needed. Earlier studies suggested that in haematopoietic neoplasms, the green tea polyphenol epigallocatechin-3-gallate (EGCG) induces cell death without adversely affecting healthy cells. We aimed at deciphering the molecular mechanism of EGCG-induced cell death in acute myeloid leukaemia (AML). A significant increase of death-associated protein kinase 2 (DAPK2) levels was found in AML cells upon EGCG treatment paralleled by increased cell death that was significantly reduced upon silencing of DAPK2. Moreover, combined ATRA and EGCG treatment resulted in cooperative DAPK2 induction and potentiated differentiation. EGCG toxicity of primary AML blasts correlated with 67 kDa laminin receptor (67LR) expression. Pretreatment of AML cells with ATRA, causing downregulation of 67LR, rendered these cells resistant to EGCG-mediated cell death. In summary, it was found that (i) DAPK2 is essential for EGCG-induced cell death in AML cells, (ii) ATRA and EGCG cotreatment significantly boosted neutrophil differentiation, and 67LR expression correlates with susceptibility of AML cells to EGCG. We thus suggest that EGCG, by selectively targeting leukaemic cells, may improve differentiation therapies for APL and chemotherapy for other AML subtypes. [source]

Acute promyelocytic leukaemia with cryptic PML-RARA fusion

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2009
K. F. Wong
No abstract is available for this article. [source]

Acute promyelocytic leukaemia presenting with a myeloid sarcoma of the tongue

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2008
S. Mohamedbhai
No abstract is available for this article. [source]

Characterization of apoptosis induced by protein kinase C inhibitors and its modulation by the caspase pathway in acute promyelocytic leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2000
Hesham M. Amin
Acute promyelocytic leukaemia (APL;M3) is a unique form of acute myelogenous leukaemia characterized by t(15;17) translocation. The induction of apoptosis via inhibiting protein kinase C (PKC) has been recently viewed as a promising tool for the eradication of several malignant disorders. In the present study, we investigated the effect of two different protein kinase C inhibitors, Gö6976 and safingol, on the induction of apoptosis in the APL cell line NB4 and its all trans retinoic acid (ATRA)-resistant variant NB4.306. The effect of the PKC inhibitors on leukaemic cells obtained from three APL patients was also studied. We also evaluated the possible involvement of the caspases in apoptosis induced by PKC inhibitors. Significant time- and concentration-dependent apoptotic changes were demonstrated using Gö6976 and safingol. In addition, our results demonstrated that the caspases were involved in the apoptosis induced by the PKC inhibitors. In conclusion, our study illustrates that the PKC inhibitors Gö6976 and safingol induce apoptosis in APL and hence could be potential therapeutic agents for the treatment of this disease. [source]

Evaluation of PG-M3 antibody in the diagnosis of acute promyelocytic leukaemia

Phase II study of arsenic trioxide and ascorbic acid for relapsed or refractory lymphoid malignancies: a Wisconsin Oncology Network study,

HEMATOLOGICAL ONCOLOGY, Issue 1 2009
JE Chang
Abstract Arsenic trioxide (As2O3) has established clinical activity in acute promyelocytic leukaemia and has pre-clinical data suggesting activity in lymphoid malignancies. Cell death from As2O3 may be the result of oxidative stress. Agents which deplete intracellular glutathione, such as ascorbic acid (AA), may potentiate arsenic-mediated apoptosis. This multi-institution phase II study investigated a novel dosing schedule of As2O3 and AA in patients with relapsed or refractory lymphoid malignancies. Patients received As2O3 0.25,mg/kg IV and AA 1000,mg IV for five consecutive days during the first week of each cycle followed by twice weekly infusions during weeks 2,6. Cycles were repeated every 8 weeks. The primary end point was objective response. In a subset of patients, sequential levels of intracellular glutathione and measures of Bcl-2 and Bax gene expression were evaluated in peripheral blood mononuclear cells during treatment. Seventeen patients were enrolled between March 2002 and February 2004. The median age was 71, and the majority of enrolled patients had non-Hodgkin's lymphoma (12/17). Sixteen patients were evaluable, and one patient with mantle cell lymphoma achieved an unconfirmed complete response after five cycles of therapy for an overall response rate of 6%. The trial, which had been designed as a two-stage study, was closed after the first stage analysis due to lack of activity. Haematologic toxicities were the most commonly reported events in this heavily pre-treated population, and comprised the majority of grade 3 and 4 toxicities. Intracellular depletion of glutathione was not consistently observed during treatment. As2O3 and AA in this novel dosing strategy was generally well tolerated but had limited activity in patients with relapsed and refractory lymphoid malignancies. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Andrographolide inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosis

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2009
Shiamala T. Manikam
Abstract Objectives The growth inhibiting potential of andrographolide was evaluated in three acute promyelocytic leukaemia cell line models (HL-60, NB4 and all- trans retinoic acid (ATRA)-resistant NB4-R2). Methods In elucidating the mechanisms of growth inhibition, a special emphasis was placed on assessing the induction of differentiation and apoptosis by andrographolide in the primary acute promyelocytic leukaemia NB4 cells. Key findings The compound was 2- and 3-fold more active in inhibiting the growth of HL-60 and NB4-R2 cells compared with NB4 cells, respectively. At IC50 (concentration at which growth of 50% of the cells (compared with medium only treated control cells) is inhibited; 4.5 ,M) the compound exhibited strong cell-differentiating activity in NB4 cells, similar to ATRA (IC50 1.5 ,M). In the presence of a pure retinoic acid receptor antagonist AGN193109, the growth inhibition of NB4 cells by ATRA was reversed, whereas the activity of andrographolide was not affected. This clearly suggested that andrographolide's cell differentiating activity to induce growth inhibition of NB4 cells most likely occurred via a retinoic acid receptor-independent pathway. At higher concentration (2 × IC50), andrographolide was an efficient inducer of apoptosis in NB4 cells. Conclusions Taken together, these results suggest andrographolide and its derivatives, apparently with a novel cell differentiating mechanism and with ability to induce apoptosis, might be beneficial in the treatment of primary and ATRA-resistant acute promyelocytic leukaemia. [source]

Preferential hypermethylation of the Dickkopf-1 promoter in core-binding factor leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2007
Rikio Suzuki
Summary The Dickkopf-1 (DKK1) gene product is an extracellular Wnt inhibitor. Hypermethylation of the DKK1 promoter results in transcriptional silencing and may play an important role in cancer development. Here, we investigated hypermethylation of the DKK1 promoter in patients with acute myeloid leukaemia (AML), especially core-binding factor (CBF) leukaemia. The methylation status of DKK1 was analysed using methylation-specific polymerase chain reaction in 47 patients with AML. DKK1 methylation was found in 14 (29·8%) patients, and more frequently in those with CBF leukaemia (6 of 12 patients), than in those with acute promyelocytic leukaemia (APL) (0 of 6 patients) (P = 0·03). In contrast, Wnt inhibitory factor-1 methylation was found in APL (4 of 6 patients) but not in CBF leukaemia (0 of 12 patients) (P = 0·001). Multivariate analyses suggested that DKK1 methylation was a risk factor for poorer overall survival. Sequential analysis using four paired samples obtained at diagnosis and relapse suggested that DKK1 methylation was involved in the progression of leukaemia. Therefore, DKK1 methylation may be involved in leukaemogenesis, especially in CBF leukaemia, and may be a useful prognostic marker in AML. [source]

Significance of persistent Auer rods and cytogenetic abnormality after first cycle of therapy for acute promyelocytic leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2007
Bakul I. Dalal
No abstract is available for this article. [source]

An unusual case of indigestion: persistence of phagocytosed Auer rods in acute promyelocytic leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2006
Christina Brown
No abstract is available for this article. [source]

Cardiac monitoring of patients receiving arsenic trioxide therapy

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2004
Dilip Unnikrishnan
Summary Arsenic trioxide (ATO) is approved for the treatment of acute promyelocytic leukaemia and is under investigation for other malignancies. We report the cardiac findings in 18 patients with haematologic malignancies treated with ATO and assess the role of cardiac factors in fluid retention syndrome observed during ATO therapy. Based on initial observations in 10 patients treated with ATO, cardiac functions in the subsequent eight patients were evaluated prospectively. Evaluation included pre- and during-treatment electrocardiograms, Holter monitoring, echocardiograms, multigated acquisition scan and cardiac stress tests if indicated. All eight patients developed fluid retention during ATO, evidenced by pulmonary congestion, oedema and pleural/pericardial effusions. No cardiac factors were identified that contributed to fluid retention. Six patients had prolonged corrected QT (QTc) compared with baseline, three developed ventricular tachycardia. Sinus tachycardia, ventricular premature contractions, and non-sustained ventricular/supraventricular tachycardia were seen during ATO treatment. Fluid retention and cardiac events did not correlate with the dose or total amount of ATO or prior anthracycline therapy. In summary, fluid overload during ATO therapy does not appear to be cardiac in origin but appears to be drug-related, and may reflect cytokine-induced capillary leak. QTc prolongation, transient arrhythmias and clinically significant arrhythmias were seen with therapeutic doses of ATO. [source]

Acute arterial occlusion as the presenting feature in acute promyelocytic leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2001
E. Kalk
No abstract is available for this article. [source]

Central nervous system relapse of acute promyelocytic leukaemia in a patient with cerebral haemorrhage at diagnosis

BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2001
M. P. Macheta
First page of article [source]

Characterization of apoptosis induced by protein kinase C inhibitors and its modulation by the caspase pathway in acute promyelocytic leukaemia

AML with bilateral retinal detachment

ACTA OPHTHALMOLOGICA, Issue 2007
E SARKADY
Purpose: To present a case of thrombotic ocular and CNS involvement complicating acute myeloid leukaemia (AML). Methods: A 42 year old woman developed blurred vision shortly after diagnosis and treatment of M6 AML. Investigations showed anterior orbital infiltration, retinal detachment and panuveitis. Iris biopsy and vitreous aspirate were negative. She developed right temporal lobe infarction and died following further CNS infarction two months after initial diagnosis. Results: Post mortem examination showed cerebral oedema, multiple cerebral infarctions and hepatosplenomegaly; both eyes contained vitreous exudates, retinal detachment and uveal thickening. Microscopy showed exudative and haemorrhagic retinal detachment, without inflammatory or neoplastic infiltrate, and bilateral uveal leukaemic infiltration with infarction. Neoplastic cells infiltrated the leptomeninges and brain parenchyma with focal vascular occlusion. Lung vessels were occluded by neoplastic cells. The spleen and bone marrow were heavily infiltrated. Partial immunophenotyping suggested a diagnosis of acute promyelocytic leukaemia (APL). Conclusions: Acute leukaemia involves the eye occurs in 39-53% cases. Visual loss is uncommon. Retinal involvement most frequently occurs in the form of superficial haemorrhages, detachment is uncommon. Acute lymphoblastic leukaemia (ALL) treated with L-asparaginase, acute promyelocytic leukaemia (APL) and non-M3 AML may present with a prothrombotic state which may be catastrophic, as occurred in this fatal case. [source]