Acute promyelocytic leukemia: evolving therapeutic strategies

Tallman, Martin S.; Nabhan, Chadi; Feusner, James; Rowe, Jacob M.

doi:10.1182/blood.v99.3.759

Cited by 359 publications

(308 citation statements)

References 83 publications

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“…Oncogene (2009) 28, 4034-4040;doi:10.1038/onc.2009published online 14 September 2009 Keywords: microRNAs; acute promyelocytic leukemia; PML/RARa Acute promyelocytic leukemia (APL) is a specific acute myelogenous leukemia subtype characterized by maturation arrest at the promyelocytic stage of development and caused by a novel fusion protein resulting from the reciprocal translocation involving the retinoic acid receptor a (RARa) on chromosome 17 with the promyelocytic leukemia gene (PML) on chromosome 15. The resulting APL-associated PML/RAR oncogene (PML/RARa) contributes to the maturation arrest of hematopoietic precursors and leukemogenesis by disrupting PML function and silencing the retinoic acid signaling pathway (Melnick and Licht, 1999;Tallman et al, 2002).…”

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confidence: 99%

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

Careccia¹,

Mainardi

Pelosi³

et al. 2009

Oncogene

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MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. A small set of miRNAs is differentially expressed in hematopoietic cells and seemingly has an important role in granulopoiesis and lineage differentiation. In this study, we analysed, using a quantitative real-time PCR approach, the expression of 12 granulocytic differentiation signature miRNAs in a cohort of acute promyelocytic leukemia (APL) patients. We found nine miRNAs overexpressed and three miRNAs (miR-107, -342 and let-7c) downregulated in APL blasts as compared with normal promyelocytes differentiated in vitro from CD34 þ progenitors. Patients successfully treated with all-trans-retinoic acid (ATRA) and chemotherapy showed downregulation of miR-181b and upregulation of miR-15b, -16, -107, -223, -342 and let-7c. We further investigated whether the APL-associated oncogene, promyelocytic leukemia gene (PML)/retinoic acid receptor a (RARa), might be involved in the transcriptional repression of miR-107, -342 and let-7c. We found that PML/RARa binds the regulatory sequences of the intragenic miR-342 and let-7c. In addition, we observed, in response to ATRA, the release of PML/ RARa paralleled by their transcriptional activation, together with their host genes, EVL and C21orf34a. In conclusion, we show that a small subset of miRNAs is differentially expressed in APL and modulated by ATRA-based treatment.

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confidence: 99%

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

Careccia¹,

Mainardi

Pelosi³

et al. 2009

Oncogene

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“…Auranofin-induced apoptosis and differentiation 753 (Grignani et al, 1994;Tallman et al, 2002). The present study is the first to demonstrate the ability of AF to induce apoptosis as well as differentiation of APL cells, on the basis of which AF could be developed as a novel drug for the treatment of APL.…”

Section: Is Kim Et Almentioning

confidence: 58%

“…ATRA therapy is more effective in inducing remission and has fewer complications than chemotherapy. Moreover, combined treatment with ATRA and chemotherapy has markedly improved remission rates and survival in APL patients (Tallman et al, 2002). Despite this improved treatment regime, approximately 30% of patients relapsed within 4-5 years.…”

Section: Introductionmentioning

confidence: 99%

Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro

Kim

Jin

Lee

et al. 2004

British J Pharmacology

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1 Acute promyelocytic leukaemia (APL) is characterized by a block in differentiation at the promyelocyte stage. Here, we describe the effects of auranofin (AF), a coordinated gold compound, on apoptosis and differentiation of APL cells. 2 Nucleosomal DNA fragmentation assay and Hoechst 33342 staining indicated that AF induced apoptosis in APL-derived NB4 cells at low concentrations (0.5-1.0 mM). The AF-induced apoptosis involved caspase-3 activation and specific cleavage of poly-ADP-ribose polymerase. 3 The AF-treated NB4 cells also produced reactive oxygen species (ROS) and cotreatment with Nacetyl-L-cysteine protected the NB4 cells from AF-induced apoptosis. 4 Expression of the CD11b cell surface marker and C/EBPe was increased when the cells were treated for 4 days with 0.3 mM AF and a physiological concentration of all-trans retinoic acid (ATRA, 5 nM). Treatment with AF in combination with ATRA markedly increased the number of cells with differentiated features, such as lobed or multiple nuclei and numerous granules and vacuoles. At these low concentrations, neither AF nor ATRA alone induced significant cell differentiation. 5 These findings suggest not only that AF induces caspase-3-dependent apoptosis via a mechanism involving ROS, but also that the combined treatment with AF and ATRA induces differentiation of NB4 cells. Our results demonstrate a novel characteristic of AF from which an effective drug treatment of APL might be developed.

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“…Induction consisting of anthracycline-based chemotherapy and ATRA are the mainstay of APL treatment [2]. A cure rate of approximately 90 % of patients who survive induction and achieve complete remission (CR) can be expected [3].…”

Section: Introductionmentioning

confidence: 99%

Successful Management of Chronic Refractory Immune Thrombocytopenia with Laparoscopic Splenectomy in a Patient with Acute Promyelocytic Leukemia

Eşkazan

Salihoğlu

Gültürk

et al. 2012

Indian J Hematol Blood Transfus

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Acute promyelocytic leukemia: evolving therapeutic strategies

Cited by 359 publications

References 83 publications

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro

Successful Management of Chronic Refractory Immune Thrombocytopenia with Laparoscopic Splenectomy in a Patient with Acute Promyelocytic Leukemia

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