The Biology of Acute Promyelocytic Leukemia and Its Impact on Diagnosis and Treatment

Lo‐Coco, Francesco; Ammatuna, Emanuele

doi:10.1182/asheducation-2006.1.156

Cited by 89 publications

(58 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Increased bone marrow FDG uptake at PET/CT is not a sufficient proof of bone marrow involvement in diffuse large B-cell lymphoma Consequently, they suggest that BMB can be omitted in case of unequivocal bone marrow involvement at FDG-PET/CT. Although the results of the study by Chen-Liang et al [1] underline the results of our previous study [2] that FDG-PET has a suboptimal sensitivity for the identification of bone marrow involvement in DLBCL, we cannot agree with their conclusion that bone marrow abnormalities at FDG-PET/CT can confidently designate advanced-stage disease. Increased focal FDG uptake in the marrow is not sufficient evidence to confirm bone marrow involvement.…”

Section: Author Contributionscontrasting

confidence: 75%

“…Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy To the Editor: With the current ATRA and chemotherapeutic regimens, over 80% of patients with de novo acute promyelocytic leukemia (APL) can be cured [1,2]. The PETHEMA group stratified APL patients into three different subgroups (low, intermediate, and high risk), by using upfront WBC count (> or <10 3 10 9 /L) and platelet count (> or <40 3 10 9 /L) [3].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy

et al. 2015

Self Cite

View full text Add to dashboard Cite

Section: Author Contributionscontrasting

confidence: 75%

mentioning

confidence: 99%

Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy

et al. 2015

Self Cite

View full text Add to dashboard Cite

“…In addition, recent evidence suggests that PML-RAR␣ is also capable of recruiting the methylating enzymes (DnmT1 and Dnmt3a), leading to the hypermethylation of the RA downstream gene promoter, resulting in transcriptional repression. 43 Hence, the ultimate result of the t(15;17) as a genetic defect is an aberration of epigenetic control in terms of both aberrant histone modification and DNA methylation at critical gene chromatin domains. Transgenic mice experiments by Pandolfi's group and others showed that the PML-RAR␣ fusion gene expressed in myeloid lineage is crucial for the pathogenesis of APL (He et al 44 ), even though other genes such as FLT-3 45 and K-ras 46 are required for a fully transformed phenotype.…”

Section: Optimization Of Regimens By Combining Atra and Ct For Apl Trmentioning

confidence: 99%

Acute promyelocytic leukemia: from highly fatal to highly curable

Wang

Zhu

2008

Blood

1,143

900

View full text Add to dashboard Cite

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia. Morphologically, it is identified as the M3 subtype of acute myeloid leukemia by the French-American-British classification and cytogenetically is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the fusion between promyelocytic leukemia (PML) gene and retinoic acid receptor ␣ (RAR␣). It seems that the disease is the most malignant form of acute leukemia with a severe bleeding tendency and a fatal course of only weeks. Chemotherapy (CT; daunorubicin, idarubicin and cytosine arabinoside) was the front-line treatment of APL with a complete remission (CR) rate of 75% to 80% in newly diagnosed patients. Despite all these progresses, the median duration of remission ranged from 11 to 25 months and only 35% to 45% of the patients could be cured by CT. Since the introduction of all-trans retinoic acid (ATRA) in the treatment and optimization of the ATRA-based regimens, the CR rate A historical view of acute promyelocytic leukemia (APL)Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML; Figure 1). Morphologically, it is identified as AML-M3 by the French-American-British (FAB) classification. Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the fusion between the promyelocytic leukemia (PML) gene and retinoic acid receptor ␣ (RAR␣). Variant chromosomal translocations (eg, t(11;17), t(5;17)) can be detected in no more than 2% of APL patients. As a special entity, APL was first described in 1957 by a Swedish author, Hillestad, 1 when he reported 3 patients characterized by "a very rapid fatal course of only a few weeks'duration," with a white blood cell (WBC) picture dominated by promyelocytes and a severe bleeding tendency. He concluded that the disease "seems to be the most malignant form of acute leukemia." More detailed features of APL were described by Bernard et al 2 in 1959, and the severe hemorrhagic diathesis has been ascribed to disseminated intravascular coagulation (DIC) or hyperfibrinolysis.In 1973, Bernard et al 3 demonstrated that APL leukemic cells were relatively sensitive to chemotherapy (CT: daunorubicin) that yielded a complete remission (CR) rate of 19 (55%) in 34 patients with APL. From then on, CT composed of an anthracycline (daunorubicin, idarubicin, or others) and cytosine arabinoside (Ara-C) was the frontline treatment of APL, and the CR rates could reach 75% to 80% 4,5 in newly diagnosed patients. However, the frequently observed aggravation of bleeding syndrome by CT, leading to high early death rate, necessitated intensive platelet and fibrinogen support. Despite such progress, the median duration of remission ranged from 11 to 25 months and only 35% to 45% of the patients could be cured by CT alone as judged by the criterion of 5-year disease-free survival (5-year DFS). 6,39 In 1985, the introduction of all-trans retinoic acid (ATRA) opened a new...

show abstract

“…In the pathology of APL, the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion protein causes a maturational block at the promyelocyte stage of myeloid differentiation (8). Under pharmacological concentrations of ATRA, the configurational modulation of the PML-RARα homodimer has been reported to cause the release of corepressors and histone deacetylases and the recruitment of coactivator complexes, resulting in the relief of transcriptional repression of APL (19).…”

mentioning

confidence: 99%

Am80 induces neuronal differentiation via increased tropomyosin-related kinase B expression in a human neuroblastoma SH-SY5Y cell line

et al. 2012

View full text Add to dashboard Cite

Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.Retinoids are known to induce neuronal differentiation, and all-trans retinoic acid (ATRA) and the synthetic retinoid Am80 have been used in differentiation therapy for acute promyelocytic leukemia (APL). In the pathology of APL, the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion protein causes a maturational block at the promyelocyte stage of myeloid differentiation (8). Under pharmacological concentrations of ATRA, the configurational modulation of the PML-RARα homodimer has been reported to cause the release of corepressors and histone deacetylases and the recruitment of coactivator complexes, resulting in the relief of transcriptional repression of APL (19). To data, RAR known as an ATRA receptor, has three known subtypes (RARα, RARβ, and RARγ) (1,14).

show abstract

The Biology of Acute Promyelocytic Leukemia and Its Impact on Diagnosis and Treatment

Cited by 89 publications

References 36 publications

Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy

Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy

Acute promyelocytic leukemia: from highly fatal to highly curable

Am80 induces neuronal differentiation via increased tropomyosin-related kinase B expression in a human neuroblastoma SH-SY5Y cell line

Contact Info

Product

Resources

About